[Retrospective study in hepatic biopsies, of hepatitis B surface antigen by the orcein method and indirect immunofluorescence methods]. A retrospective study of the HBsAg was done in 56 liver biopsies of children less than 12 year-old and 78 biopsies of adults. The study was performed by orcein stain and indirect immunofluorescent method. In 23 of the adults patients, the serological detection of HBsAg and antibodies (HbsAb) was determined by reverse passive haemagglutination technique. The adults patients' histological dianosis were variable and included acute or chronic hepatitis (20.5%) and cirrhosis (24.4%). Orcein was positive in 7 and IFI in 6 cases; 5 biopsies were positive by both methods. The highest incidence of HBsAg was seen in active cirrhosis (75%), including two cases of alcoholic cirrhosis. In the 23 serologically studied patients, 15 cases were HBsAg negative and 3 were HBsAg positive both in the liver and serum; only 2 cases showed discrepancy between these results. Three patients were HBsAb positive and HBsAg negative both in the liver and serum. All children biopsies were HBsAg negative. Among these patients, 26.8% had acute or chronic hepatitis and 10.7% cirrhosis. Serological and tissue techniques for HBsAg and HbsAb detection have different sensitivity. This should be kept in mind when studying the incidence of hepatitis B virus related to liver diseases.


Continuous dielectrophoretic separation of cell mixtures. Use of stream-centered dielectrophoresis (1-4) produced continuous separations on three cell mixtures (1) Chorella vulgaris with Netrium digitus, (2) Ankistrodesmus falcatus with Staurastrum gracile, and (3) Saccharomyces cerevisiae with Netrium digitus. Maximal separations were obtained for these mixtures of live cells at 100 kHz, 600 kHz, and 2.0 MHz, respectively. The technique was restricted to a frequency range of 0.01-32 MHz, and to suspensions of low conductivity in which microorganisms such as these algae and yeast are tolerant. Extension, however, to cellular organisms requiring higher osmolarity is readily feasible through the use of nonionic solutes such as sucrose, mannose, glycine, etc.


Electrokinetic study of the reactions of peritoneal macrophages and eosinophils with IgG immune complexes. Electrophoretic light scattering (laser Doppler electrophoresis) has been employed to study the effects of guinea pig IgG immune complexes on the electrophoretic mobility distributions of guinea pig resident peritoneal cells. The resident population of cells is composed of macrophages (approximately 75%) and eosinophils (approximately 25%). These cells were separated according to the well-established method of Boyum. Populations of resident macrophages, eosinophils, and the unfractionated samples were incubated with soluble immune complexes, antigen alone, or antibody alone. The mean mobility of the resident macrophages decreased approximately 60% when incubated in the presence of immune complexes, although no effect could be discerned in the presence of antigen or antibody alone. The width of the resulting macrophage mobility distribution was larger than that of the control distributions, with a broad shoulder on the high-mobility side, indicating a heterogeneous response of the macrophages to the immune complexes. Eosinophils react in two distinct fashions. One population of eosinophils is present near the control experiments. The second population reacts in a manner very similar to that of macrophages. This suggests that at least two populations of eosinophils are present in the unstimulated guinea pig peritoneal cavity. Results that are intermediate between these two cases are found when unfractionated samples are studied.


Discriminant analysis on cells from developing squamous cancer of the respiratory tract. Cytologic preparations made from the tracheobronchial tree taken by the Schreiber catheter have been scanned by three color microphotometry. The digitized cell images were processed by the analytical cytodiagnostic programs of the TICAS system. Cells were sorted into two control groups and five groups of increasing atypia ranging from normal epithelium to invasive squamous cell carcinoma. Standard statistical tests, including Wilk's Lambda, Rao's V, and the Kruskal-Wallis tests are performed on these subsets of cell image features. This study demonstrates that discriminant analyses permit differentiation between normal cells and those from marked atypia or carcinoma and that the classification achieves a high degree of agreement with visual assignment.


Visualization of mitochondrial coupling factor F1(ATPase) by freeze-drying. It is known that the negatively stained preparations of inner mitochondrial membrane display characteristic approximately 9 nm F1 (ATPase) knobs projecting from the matrix surface. Freeze-etch studies have reported the absence of such knobs from the "etched" surface of the inner mitochondrial membranes. We have demonstrated their presence on the surface of SMP (submitochondrial particles) prepared by freeze-drying for transmission electron microscopy. This identification has been substantiated by comparison with freeze-dried TU particles (trypsin-urea treated SMP) that are devoid of F1 (ATPase). It has been suggested that a layer of water molecules is strongly adsorbed to the surface of SMP and does not sublime during normal freeze-"etching."


On the mechanism of binding of human lymphocyte products to guinea pig macrophages. When lymphocytes from a majority of patients with cancer are incubated with encephalitogenic factor, a lymphocyte product is released that reduces the anodic electrophoretic mobilities of guinea pig macrophages and fixed, tanned sheep erythrocytes. Although these reactions are not specific for cancer, it is distinctly possible that in patients with cancer, products from stimulated lymphocytes are capable of altering the surfaces of the patients' own macrophages, thereby modifying the course of their disease. In this paper, we attempt to elucidate some mechanisms for the binding of lymphocyte products to macrophages, such as occurs in the macrophage electrophoretic mobility (MEM) test, since this may be of general interest. Binding of lymphocyte product to macrophages has been monitored by measurements of their electrophoretic mobilities and by electron microscopic determination of the density of binding of electron-dense, cationic colloidal iron hydroxide particles to their surfaces. The results show that the lymphocyte products reduce the net surface negativity of the macrophages by (coulombic) binding of this net positively charged material to sialic acids at the macrophage surface. Product-binding can be prevented by prior treatment of the macrophages with neuraminidase. It appears that only a minority of sialic acids are involved in the binding process, which occurs without demonstrable blocking of adjacent sialic acids or redistribution of such sites over the macrophage surface. Parallel experiments with fixed tanned erythrocytes also suggest that binding of lymphocyte product is not solely determined by surface sialic acids, although it cannot occur without them.


Surface thermodynamics of leukocyte and platelet adhesion to polymer surfaces. Adhesion of leukocytes and platelets to solid substrates of different surface tensions and hence different wettability is studied from a thermodynamic point of view. A simple thermodynamic model predicts that a cellular adhesion should increase with increasing surface tension of the solid substrate if the surface tension of the medium in which the cells are suspended is lower than the surface tension of the cells. If the surface tension of the suspending medium is higher than that of the cells, the opposite behavior is predicted. These predictions are borne out completely by neutrophil adhesion tests, where the surface tension of the aqueous suspending medium is varied by addition of dimethyl sulfoxide (DMSO). Platelet adhesion experiments also confirm these predictions, the only difference being that surface tensions of the suspending medium above that of the platelets cannot be realized, owing to exudation of surface active solutes from the platelets. Utilization of the thermodynamic prediction that cellular adhesion should become independent of the surface tension of the substrate when the surface tensions of the cells and that of the suspending medium are equal leads to a value of the surface tension of neutrophils of 69.0 erg/cm(2), in excellent agreement with the value obtained from contact angles measured on layers of cells.


The dissociation and separation of bovine adenohypophysial cells. Bovine adenhypophysial tissue was dissociated by sequential enzymatic incubation in a continuous flow system. Dispersed cells separated into discrete fractions after centrifugation in isopycnic bovine serum albumin gradients. The dispersed and separated cells were prepared for microscopic identification and differential counts by centrifugal cytology. Radioimmunoassays for LH, FSH, TSH, and Prl were used to corroborate the differential counts and determine the homogeneity of the fractions. The thyrotrophs banded at an average density (rho) of 1.0417, the FSH-secretory cells at rho = 1.0597, the LH-secretory cells at rho = 1.0458, and the Prl-secretory cells at rho = 1.0126. A 7-16 fold enrichment of different cell populations was possible. In bovine hypophyses each hormone appears to be formed by specific cells: the average TSH concentrations of the thyrotrophs were 5.1 pg/cell for LH- and FSH concentration were 4.7 and 4.9 pg/cell for LH- and FSH-secreting cells, respectively. The average Prl concentration was 4.9 pg/cell for Prl-secreting cells.


The influence of cell surface receptor clustering on the thermodynamics of ligand binding and the kinetics of its dissociation. We show that an equilibrium model for the clustering, by divalent ligand, of homogeneous plasma membrane-bound divalent receptors that do not change conformation predicts Scatchard plots with positive second derivatives (concave up). The result is thermodynamically indistinguishable from predictions based upon receptors that are heterogeneous for ligand, or that change conformation in a negatively cooperative way when ligand binds. A more general formulation of the theory, which allows application to dissociation kinetics, predicts that the dissociation of labeled ligand is accelerated in the presence of excess cold ligand and, moreover, that the accelerated dissociation has at least two components. The theory is briefly illustrated by fitting five different sets of data, at several temperatures for two different systems, with parameter values that are well within physically meaningful ranges. The model presented is the simplest and least ad hoc explanation thus far proposed as the basis for the kinetic phenomena, and raises the possibility that the numerous experiments in which such data are observed are primarily minifestations of cell surface clustering.


A theoretical model for adhesion between cells mediated by multivalent ligands. A theoretical model is developed for cell-to-cell binding by bivalent ligands that can bind to mobile receptors on the cell surfaces. Monovalent inhibitors that can bind either to receptors or ligands are also included. For symmetrical ligands, that is, ligands in which both binding sites are the same, it is shown that crosslinking of receptors on each cell will interfere with intercellular bridge formation. At equilibrium, such interference is not drastic, but if the crosslinks can form before the cells are brought into contact, crosslinking may greatly impede the rate of intercellular binding. Comparison is made with experiments, and the importance of receptor mobility is discussed. It is noted that ligands can also bind a cell to itself or to a surface.


Membrane surface properties of sheep erythrocytes, an immunological reagent, after different treatments as reflected by partition in two-polymer aqueous phases. Sheep erythrocytes (E) which, with or without certain treatments, are currently used as "immunological reagents" to detect cells with specific receptors (by rosette-formation) have been partitioned in two-polymer aqueous-phase systems selected so as to reflect charge-associated or lipid-related membrane surface properties. We have found that the partitioning behavior of E is not affected in these phases by reacting the cells with anti-E antibody (either IgG or IgM), forming EA. The additional binding of complement to the cell-antibody complex, forming EAC, results, however, in a marked decrease in the partition coefficient, K. Apparently both the charge-associated and hydrophobic properties reflected by partitioning remain accessible to the phase polymers when the cells are coated with antibody, but are not with the addition of complement. It is interesting that EA can still rosette with T-lymphocytes (14), a property of E, while the additional coating with complement results in EAC which does not appreciably do so (26). Neuraminidase or trypsin treatments of E, which yield Es having quite different rosetting properties with T-lymphocytes (14), cause increased Ks and unchanged Ks, respectively, in phases reflecting lipid-related surface properties. Either treatment causes reduced Ks of E in charged-phase systems. Neuraminidase treatment also results in a reduced electrophoretic mobility of E, while trypsin treatment is not detectable by cell electrophoresis (25). We are currently studying the possible usefulness of employing cell electrophoresis and cell partitioning in charged-phase systems jointly to obtain information on events occurring at the shear plane versus those occurring deeper in the membrane.


Separation of T and B lymphocytes from various mouse strains by density gradient electrophoresis. T and B mouse spleen lymphocytes were separated by density gradient electrophoresis on the basis of their surface charge. In all strains examined, the T lymphocytes were found in the high mobility fractions and the B in the low. The T and B cells were separated completely in most fractions, with some overlapping in the middle. Significant differences were found in the electrophoretic distribution profiles between the strains: C57BL/6j, C57BL/10j, (BALB/cXC57BL/6j)F1, and all the following: B6.C-H-2d/cBy (congenic to C57BL/6j), BALB/c, CBA/H/T6j, C57BL/10Sn, and C3H. The C57BL/6j and the (BALB/cXC57BL/6j)F1 cells appear more heterogeneous as far as electrophoretic mobility is concerned. Almost all the other strains give two major peaks. Moreover, the high mobility areas are less populated in the C57BL/6j and the (BALB/cXC57BL/6j)F1 animals than in all the others. The above differences were found consistently when cells prepared by different methods were electrophoresed. It is concluded that the surface charge of lymphocytes may be genetically determined. Possible dependency on the H-2 complex or non-H-2 areas is discussed.


Effects of ovarian hormones on cell membranes in the rat uterus. I. Freeze fracture studies of the apical membrane of the liminal epithelium. Freeze fracture techniques have been used to study the apical membrane of cells of the luminal epithelium of the rat uterus under various hormonal regimes. In the ovariectomized but otherwise untreated rat, intramembranous particles (IMPs) occur at a density of 1395 +/- 122 per micron 2; they appeared spherical and uniformly distributed. After 3 days treatment with estrogen, no change in appearance or density was found, but 3 days of progesterone treatment produced a significant increase in IMP density to 1622 +/- 104. Treatment with progesterone, with an additional dose of estrogen on day 3, is known to produce an epithelium receptive to the implanting blastocyst. In these conditions, the IMP density rose to 3818 +/- 337: rod-shaped particles and aggregations of IMPs were seen, and some particle arrays resembling gap junctions, in addition to the isolated spherical particles.


Analysis of cellular DNA distributions. I. G2/G1 channel ratios. In the influencent-flow cytophotometric measurement of cellular DNA content the DNA distributions usually have two peaks. The second peak, which corresponds to the 4C DNA content of G2 and M cells, is often positioned at lower values of DNA content than twice that of the 2C DNA peak which contains G1 cells. Computerized numerical analyses were performed on artificial DNA distributions in which the proportion of S-phase cells was varied. It was demonstrated that the contribution of late S-phase cells to the 4C DNA peak in the histogram shifts the second peak to a position below twice the 2C DNA value. Also, increasing the coefficient of variation of the DNA measurement shifts the second peak position to lower values. A group of 33 DNA distribution histograms we found to have an average G2/G1 peak position ratio of 1.90, in keeping with typical values obtained from the numerical analysis of the artificial populations.


Centrifugal elutriation (counterstreaming centrifugation) of cells. Lindahl first described the separation of cells by velocity sedimentation utilizing a special technique (counterstreaming centrifugation) that was later modified slightly and renamed centrifugal elutriation. Centrifugal elutriation has been applied, with variable degrees of success, to the separation of hemopoietic cells, mouse tumor cells, testicular cells, and a variety of other specialized cells as well as cells in particular phases of the cell cycle. The capacity of the elutriator to separate large numbers of cells is its chief advantage. The purities of the separated cells have not been compared with the purities of cells separated by other methods in most cases; such comparisons would permit more sophisticated comparison of elutriation with other techniques for velocity sedimentation.


Characterization of murine T and B cells by computerized microphotometric analysis. Splenocytes and column-separated T cells are differentiated into subpopulations of T and B cells on the basis of computer-assisted morphometric analysis of Feulgen-positive nuclear DNA. Differentiation is based upon the analysis of computable image information related to DNA distribution patterns. The technique at the present time does not allow immunofluorescent and morphometric measurements to be made on a given cell. However, the differentiation obtained by using descriptors proven capable of detecting pure populations of T and B cells shows excellent agreement with the differentiation obtained by immunofluorescence analysis. The descriptors and decision rules used the discrimination among splenocytes are reproducible from one experiment to another and remain valid for the differentiation of lymphocytes from animals of different sex and strain.


Subclassification of murine T cells by computerized microphotometric analysis. Splenocytes separated by physical means and classified as T cells bay immunologic tests and computerized microphotometric analysis are differentiated into subgroups by analysis of the distribution patterns of Feulgen-positive nuclear DNA. In like fashion T cells obtained as purified preparations after separation on a nylon column, and accepted as T cells by micromorphometric analysis were subjected to further computerized morphometric analysis of nuclear DNA to form subgroups of cells. In each case, the number and composition of the detected subgroups were consistent. The classification does not appear to reflect any obvious phases of the cell cycle and is not dependent upon the sex and strain of mice from which the cells were obtained.


Cytotoxic and fluorescent assays for thymocyte subpopulations differing in surface thy-1 level. A number of analytical techniques for distinguishing and separating the "high theta" "low theta" subpopulations of mouse thymocytes have been compared. A differential cytotoxic assay was compared to a quantitative immunofluorescent assay on individual cells using flow cytofluorometry and cell sorting. Conventional anti-Thy-1 antisera were compared with a monoclonal IgM anti-Thy-1. The monoclonal reagent greatly improved both types of assay, eliminated a number of artifacts and allowed either procedure to be used to give a clear distinction, based on Thy-1 level, between the two subpopulations. The distribution of Thy-1 on thymocytes is bimodal, rather than continuous. These separate "high theta" and "low theta" categories each includes a population a population of dividing cells.


Morphometric analysis of B2cAMP induced reverse transformation in synchronized CHO cells. Synchronized tranformed and reverse-transformed (by 10(-3) M B2cAMP) CHO-K1 cells, growing adherent to plastic, are characterized by means of geometric and densitometric parameters at the level of both the entire cell and of the nuclei at various time intervals after selective miotic detachment. Transformed and reverse-transformed cells triple-stained with Feulgen, Napthol Yellow S, and periodic acid-Schiff appeared very similar in terms of integrated optical density (IOD), related to either polysaccharides, protein, or DNA amount. On the other hand, a shift from a polygonal to a spindle-shaped morphology is a accompanied by a significant decrease in both form factor and average optical density (AOD) of intact cell and nuclei, which are the most conspicuous measured changes caused by B2cAMP, in addition to a lengthening of the cell cycle duration. In both control and treated cells, important and parallel cell-cycle-dependent modulations of geometric and densitometric parameters are also observed, for both the cytoplasmic (i.e., cell morphometry) and DNA space (i e., nuclear morphometry). Specifically, the modulation in nulear morphometry during G1, S, G2, and M phases confirms previous findings on synchronized HeLa cells. The optical density threshold-dependence of geometric parameters shows that, while becoming fusiform, the cytoplasm of reverse-transformed cells had a particularly low optical density precisely in the polar area. Utilization of such an approach in the development of an objective morphological classification of all cell lines grown as monolayers "in vitro" is also discussed.


Assessment of immunocytochemical techniques with particular reference to the mixed-aggregation immunocytochemical technique. Antibody-mediated assays are believed to be the most sensitive and specific techniques for antigen localization available to date, but they need extensive controls if specific and quantitative results are to be obtained. Problems arise from both the antibody source and the antigen in the tissue preparation. Specificity of the antibody is often difficult to prove in any direct or indirect antibody technique. When markers are coupled to antibody, binding and diffusion properties of the antibody are changed. Diffusion of antigen from its site and loss of antigenic determinants due to procedures for preserving morphology are two other main problems. The mixed-aggregation immunocytochemical technique provides another way of checking the selectivity of the antibody, since a cross-reactive antigen introduced into the section and not the antibody itself is what is seen. Quantitative studies using localization of lactic dehydrogenase isoenzymes in human skeletal muscle fibres show that the technique fulfils most of the present criteria on precision, specificity and validity for determination of enzymes. It also ensures that more than 80% native antigen in frozen sections is fixed and is two to three times more sensitive and selective than the direct antibody technique.


Isoprinosine increases the antitumor action of interferon. The association of relatively low doses of interferon with an immunostimulant, isoprinosine, enhanced the antitumor effect of interferon. Each mouse was inoculated with 10(6) Crocker Tumor 180/TG cells. The best results were obtained when both interferon and isoprinosine were injected three times a week for 1 month. Under these conditions, the mean survival time increased from 26 days in the controls to 45 days in the interferon-treated group to 64 days when both agents were used. Isoprinosine alone had no effect. The final survival rate increased from 1 mouse out of 50 mice in the control group to 10 mice out of 50 in the interferon-treated groups and to 25 mice out of 50 with the combined treatment.


Preservation of carrageenan-induced immune suppression with alleviation of toxicity in aprotinin-treated mice. Although the immunosuppressive effect of carrageenan was unimpaired in aprotinin-treated mice, the extent of intravascular coagulation induced by this macrophage toxic agent was substantially reduced. Use of antiproteases such as aprotinin may prove beneficial in management of this adverse side effect of certain immunotherapeutic agents.


E-type delayed fluorescence depolarization, technique to probe rotational motion in the microsecond range. E (eosin)-type delayed fluorescence depolarization studies extend the time range for the measurement of rotational diffusion to microseconds and ms, thereby allowing investigation of slow rotational movement of macromolecules like membrane proteins. An apparatus is described for the determination of time-dependent anisotropy in this interesting time range. The method has been tested on eosin-labelled cytochrome P-450 incorporated into phospholipid membrane vesicles.


A millipore--blue dextran affinity binding system. Blue dextran has been adsorbed to millipore filter discs in a linkage stable under a variety of conditions. These discs have been to bind lactic dehydrogenase, which may then be specifically eluted with NADH, one of its substrates. In contrast, another enzyme, alkaline phosphatase, not expected to bind to blue dextran, was indeed completely recovered in the filtrate.


Vitamin A effect on tumor angiogenesis.

Vitamin A effect on tumor angiogenesis. The inhibitory effect of vitamin A on tumor establishment and growth has been studied in two animal models. The C57L/J hepatoma, when placed in C57L/J mice receiving inoculations of vitamin A, showed slow growth and the hosts had significantly prolonged survival over untreated mice. The V-2 carcinoma, when implanted in the corneas of New Zealand white rabbits receiving injections of vitamin A, showed decreased vascular response in the limbic vessels. The absence of an induced vascular response prevents vascularization of the tumor and subsequent tumor growth. The evidence suggests that vitamin A may exert its inhibitory effect by modifying the normal vascular response to neoplastic tissue.


Heterogeneity, immunological comparison and concentration profiles of alpha-fetoproteins derived from late-gestational and early postnatal mouse tissue. Four distinct alpha-fetoprotein (AFP) species were separated by ion-exchange chromatography of the approximately 70 000 dalton fraction of an extract of late-gestation fetal mice. Although chromatographicaly heterogeneous, antigenic differences among the AFP species resolved were not detected using classical double-diffusion methods. Analysis of the AFP contribution to total body saline-extractable protein of fetal and neonatal mice revealed an abrupt decrease in the fetal AFP contribution to total body saline-extractable protein commencing after the 18th day of gestation.


Plasma pregnancy-associated alpha 2-glycoprotein concentrations in complications of pregnancy and foetal abnormality. Maternal plasma concentrations of pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) were measured in normal pregnancy and in pregnancies complicated by apparent threatened abortion, pre-eclampsia or intrauterine growth retardation (IUGR). alpha 2-PAG levels were significantly decreased in those women who spontaneously aborted and in those with foetal death, but were unaffected in patients who threatened to abort and in whom pregnancy continued successfully. Concentrations of alpha 2-PAG were also unaffected in subjects with mild or severe pre-eclampsia and in those with IUGR. Patients with high alpha-foetoprotein levels associated with foetal abnormality also had normal alpha 2-PAG levels for stage of gestation. The possible immunological implications of these findings are discussed.


Combined autoradiography and histochemistry: the simultaneous detection of 6-3H thymidine and acid phosphatase activity in cryostate sections. A method is described for the simultaneous demonstration of 6-3H thymidine incorporation and acid phosphatase activity in cryostae sections of mouse thymus. The method enables a comparison of mitosis and acid hydrolase activity to be made in the same tissue section. In 8-week-old mice acid phosphatase positive cells reprsent 1.23 +/- 0.06% of the total population and 8.4 +/- 0.27% of the cells incorporate tritiated thymidine. Acid phosphatase activity can be used to estimate cell autolysis and death. The implication of the method in relation to tissue dynamics is discussed.


Ribonucleotides in DNA newly synthesised in 3T6 cells in vivo. Within the field of DNA replication, considerable interest has focused in recent years on the mechanism of initiation of synthesis of DNA molecules. In vitro replication systems from Escherichia coli have been instrumental in uncovering a priming function fo9r ribonucleotides on the earliest intermediates of DNA polymerisation in vitro and in identifying the proteins involved. In vitro replication systems from mammalian cells that permit the use of the phosphate-transfer method for detection of RNA-DNA junctions as well as direct labelling of the RNA moiety of the molecules have suggested a similar role for ribonucleotides in DNA synthesis in eukaryotes. However, the existence of this mechanism in mammalian cells in vivo has not been established. Here we report the first evidence that a significant proportion of the earliest intermediates in mammalian DNA polymerisation in vivo do, in fact, possess ribonucleotides, presumably because their synthesis was initiated with one or more ribonucleotides.


Natural occurrence of 2-5A in interferon-treated EMC virus-infected L cells. Until now the interferon-mediated 2'-5' adenine oligonucleotide inhibitors (2-5A) of cell-free protein synthesis have not been detected in intact cells. Here we report their natural occurrence in interferon-treated, EMC virus-infected mouse L cells in amounts consistent with the idea that they play a part in the inhibition of virus growth.


Ca2+ is essential cofactor for trypanocidal activity of normal human serum. Normal human serum has been known to exert a cytotoxic effect on Trypanosoma brucei subspecies for nearly 80 yr. But in spite of many attempts, no trypanocidal factor was found in human or baboon serum, until Rifkin demostrated a high density lipoprotein (HDL) in normal human serum with trypanocidal activity. The conclusion that this was the trypanocidal factor was supported by the report that serum from patients with Tangier disease, characterised by a severe deficiency of HDL, lacked trypanocidal activity. We report here that Ca2+ is an essential cofactor for the trypanocidal activity of normal human serum, in which alpha2 macroglobulin (alpha 2) might function as a Ca2+-carrier. We further show that D-glucose, D-fructose and D-mannose can suppress the trypanocidal action of normal human serum, whereas glycerol has the opposite effect.


Actinobacillus seminis infection in sheep in the Republic of South Africa. III. Growth and cultural characteristics of A. seminis. Bacteriological tests were done on a large number of different strains of Actinobacillus seminis and also, repeatedly, on the same culture or on different cultures taken periodically from the same donor animal. These tests were also applied to strains of A. seminis representing different serological types, which in turn were compared with strains of Brucella ovis. The tests as applied proved that A. seminis strains have defined, morphological, staining, cultural and biochemical properties, although they can generally be regarded as biochemically inactive. Growth was greatly enhanced on media enriched with blood or serum and also more luxuriant when incubated in a carboxophilic atmosphere. Nitrate reduction was found to be a variable characteristic, as it was more often negative, while weakly positive and negative reactions for hydrogen sulphide production were encountered with equal frequency. On the basis of their bacteriological properties, the strains representing the different serological types can be divided into 2 groups. Strains belonging to the first of these groups conform to the earlier description of A. seminis by Baynes & Simmons (1960) and are usually catalase positive and oxidase negative, while those in the second group more closely resemble Histophilus ovis described by Roberts (1956), and produce variable reactions on the catalase and oxidase tests. Although growth did occur aerobically and was more luxuriant in a carboxyophilic atmosphere in all strains, it was always much slower for strains resembling H. ovis. Similarly, the growth produced by these strains was poorer and more irregular on ordinary nutrient media and, although greatly enhanced and more regular in all strains on enriched media, it was again much slower for these strains. In all stages of development, the colonies of strains similar to H. ovis were always slower and more transparent in appearance, and tended to remain low convex and undifferentiated. Packed organisms of these strains were light yellow (lemon) in colour in contrast to strains resembling A. seminis, which had a greyish-white appearance. A. seminis and B. ovis can clearly be distinguished on their morphology, Stamp staining reaction on both semen and culture smears, colonial morphology, the delayed colony development of B. ovis and sensitivity to dyes and antibiotics.


Differential suppression of experimental allergic diseases in rats infected with trypanosomes. PVG/c rats, infected 3 days previously with 10(3) Trypanosoma brucei brucei S.42 organisms failed to develop adjuvant disease in response to an intradermal inoculation of mycobacterial adjuvant. By contrast, similarly infected rats, immunized with heterologous brain and spinal cord in Freund's complete adjuvant with pertussis vaccine as a secondary adjuvant, developed clinical signs of allergic encephalomyelitis (EAE) at least as severe as those in uninfected rats. Delayed hypersensitivity reactions to PPD were depressed in trypanosome-infected, adjuvant-injected rats, as were the reactions to myelin basic protein in infected rats developing EAE. There appeared to be no cross-reactivity between trypanosomal antigen and myelin basic protein which could account for the lack of suppression of EAE. It is suggested that the different extent to which autoimmunity is involved in these two experimental allergic diseases may account for the differential suppressive activity of trypanosome infections upon them.


Sinus arrest in diaphragmatic myocardial infarction: treatment of power failure with atrial pacing. Sinus arrest occurred in a patient with acute diaphragmatic myocardial infarction associated with right ventricular infarction. Cardiac output fell dramatically despite maintenance of a junctional rate of 72. Ventricular pacing at rate 82 and dopamine administration resulted in only slight hemodynamic improvement. Atrial pacing at rate 84 restored normal cardiac output until resumption of sinus node activity. These results suggest that atrial contraction is important for the maintenance of ventricular function in some patients with acute infarction, and may be of particular importance in the presence of right ventricular infarction. Temporary atrial or atrioventricular sequential pacing may be of great hemodynamic benefit in selected patients with conduction defects complicating myocardial infarction.


A new concept for atrial triggered pulse generators. In order to avoid the potential risk of a short refractory period and the inconvenience of the electronic blocking mechanism at the highest synchronous rate with the conventional atrial triggered pulse generator, two more functions have been added to the normal atrial triggered (VAT) pulse generator. First, it has been designed to be ventricular inhibited; second, a highest synchronous rate detector has been added. When the highest synchronous rate of about 140 is exceeded, the atrial signals are blocked and the frequency of the basic rate generator is increased to about 130. Two patients could hardly feel the change from atrial triggered pacing to ventricular inhibited stimulation, and both were able to work at higher loads with this type of pacing compared with the conventional atrial triggered pulse generator.


Ventricular tachycardia and ventricular fibrillation in patients with short P-R intervals and narrow QRS complexes. Eleven patients with short P-R intervals and narrow QRS complexes had ventricular tachycardia due to organic heart disease: mitral valve prolapse with mitral insufficiency (2 patients); alcoholic (?) cardiomyopathy (2 patients); and coronary artery disease (7 patients). Intracardiac studies showed short A-H intervals during sinus rhythm in all cases. The onset of ventricular fibrillation (which, to our knowledge, has not been observed in patients having short P-R and A-H intervals coexisting with narrow QRS complexes) was documented in 4 cases. Only 1 patient (with quinidine syncope) had been premedicated. In the 3 other patients the episodes of ventricular fibrillation appeared during bouts of atrial fibrillation with rapid ventricular rates which could have been an exprerssion of the "enhanced A-V conduction" that had been manifested in sinus beats by short P-R and A-H intervals. In clinical settings and physiological conditions proven to be hemodynamically unstable (such as transient ischemia or acute myocardial infarction) these rapid ventricular rates could have led to ventricular fibrillation; directly because of the R-on-T phenomenon, and/or indirectly due to decreased coronary perfusion. Ventricular tachycardia and ventricular fibrillation due to organic heart disease probably occur more often than suggested by the few reported cases in the literature. Its significance, however, has to be clarified by further prospective studies.


The use of balloon-tipped electrodes for permanent cardiac pacing. A new balloon-tipped ventricular endocardial electrode for permanent artificial cardiac pacing is described. Following transvenous insertion of the electrode to the right ventricular apex, the distal balloon is inflated with contrast material in order to wedge the electrode tip between or beneath trabeculae and prevent displacement. fifty-nine electrodes were implanted, including a second generation type incorporating a wedge tip as well as the balloon. The incidence of displacement was 17% with 10% of cases being early, and 7% late. Early in the series, 50% Urografin was used to inflate the balloon and this resulted in premature deflation and early electrode displacement in two of the nine patients. When the concentration of Urografin was reduced, the balloon remained inflated for a longer period and the incidence of early displacement was reduced to 8%. However, there was still a late displacement of 8%. Only one wedge-tipped balloon electrode displaced. This electrode had a faulty sealing mechanism and the balloon could not be adequately inflated. There was a 3% incidence of early and a 3% incidence of late threshold problems with the electrode. However, name of the wedge-tipped balloon electrodes exhibited this problem. It was concluded that this new electrode did not fulfill its objectives. The total electrode failure rate, including displacements and episodes of high threshold was approximately 24%.


The response of regular re-entrant supraventricular tachycardia to right heart stimulation. The study was designed to assess the effect of various forms of right atrial or ventricular stimulation on the termination of re-entrant "supraventricular" tachycardias. Standard electrophysiological techniques were used in 81 patients to study 86 stable tachycardias. All tachycardias were initiated by single or double atrial or ventricular premature stimuli or incremental atrial pacing. Eight groups of tachycardia circuit were defined in terms of the anterograde and retrograde pathways. Termination of each tachycardia was studied by atrial underdrive, ventricular underdrive, rapid atrial stimulation and single or double atrial and ventricular premature extrastimuli. Intranodal re-entrant tachycardias formed 33% of the total and WPW tachycardias as a whole formed 55% of the total number of arrhythmias. The remainder were comprised of atrial tachycardia (5%), tachycardias in association with a partial AV nodal bypass (3%) and pre-excited tachycardias (5%). A single atrial extrastimulus was most effective where the circuit involved the right atrium. Atrial underdrive was consistently less successful than a single atrial extrastimulus in all groups. Rapid atrial pacing was effective in all groups, but caused transient atrial flutter or fibrillation in a proportion of each group except one. Ventricular underdrive stimulation was most effective in those groups where the right ventricle was involved in the circuit, but tended to be less effective than programmed single or double ventricular extrastimuli. Pacemakers designed to deliver appropriately timed single or double extrastimuli may offer an important alternative to other pacing modalities.


Myopotential inhibition of demand pacemakers: etiologic, diagnostic, and therapeutic considerations. Myopotential inhibition of demand pacemakers is a common phenomenon and is responsible for a greater degree of morbidity and possible mortality in patients with pacers. Significant electrical potentials generated by contracting muscle mass gain entry into the pacemaker circuitry causing inhibition of pacemaker activity. Intraoperative and bedside maneuvers can readily precipitate the problem and allow for accurate diagnosis. Holter monitoring frequently can also serve to establish the diagnosis. Pacemaker repositioning, replacement with a bipolar system, use of a fixed-rate pacemaker, and pacemaker "sleeves" are possible intraoperative therapeutic methods. External sensitivity adjustable pacemakers would seemingly allow for noninvasive solutions to the problem.


Ventricular tachycardia terminated by carotid sinus massage. Carotid sinus massage affects supraventricular arrhythmias primarily through vagotonic effects on the sinus and AV nodes, but vagal innervation of the ventricle also exists and has been shown to have functional significance. The case presented here illustrates an unusual example of a ventricular tachycardia that was repeatedly converted to normal sinus rhythm by carotid sinus massage following administration of digoxin. The clinician should be aware that a wide QRS-complex tachycardia that responds to carotid sinus massage is not necessarily supraventricular in origin.


Runaway pacemaker. A case report with a runaway rate of 2100 ppm. A case of runaway pulse generator is described. A Vitalith C-23 developed runaway on the 13th postoperative day, without any preceding changes in the rate or amplitude of the pulse generator spike. The rate of runaway was 2100 pulses per minute (ppm), one of the highest rates ever reported. The ventricle was not captured by the runaway pulse generator, but was paced effectively by a temporary demand pacemaker (Medtronic 5880A) which was left in case of displacement of the implanted pacing lead. The reasons why the temporary pacemaker was not inhibited are discussed.


Pacing-induced alternate Wenckebach periods: incidence and clinical significance. Alternate Wenckebach periods have been defined as episodes of 2:1 atrioventricular (AV) block in which conducted P waves exhibit progressive PR prolongation until two or three successively blocked P waves. Ocurrence of this phenomenon during atrial pacing has been established. Thirty-six patients were studied and right atrial pacing was achieved at increasing rates up to 350 beats/min in order to induce alternate Wenckebach periods. His bundle recordings were obtained in every patient. The patients were subdivided into three groups according to the AV nodal conduction time (AH interval): normal AH (75-130 ms) was present in 17 patients, short AH (70 ms) in 13 patients and prolonged AH (130 ms) in eight patients. Alternate Wenckebach periods were observed in 29 patients (80.5%). In every patient alternate Wenckebach periods occurred at the AV node level. Atrial pacing failed to induce alternate Wenckebach periods in seven patients, six of whom belonged to the short AH group. In four patients 3:1 block never appeared because of block at the atrial level. Two patients presented 2:1 and 3:1 infrahissian block without significant AH prolongation. The remaining patient developed atrial fibrillation. Alternate Wenckebach periods were observed in six of nine patients after intravenous atropine. This study suggests: 1. pacing-induced alternate Wenckebach periods at the AV node level are a physiologic phenomenon; and 2. total or partial bypass (or accelerated AV conduction) atrial refractoriness or vulnerability or block at a lower level may prevent its occurrence.


Air entrapment as a cause of transient cardiac pacemaker malfunction. Air within a pacemaker pocket may cause transient malfunction of a replacement unipolar cardiac pacemaker. This was noted in a patient in whom entrapped air prevented tissue contact of the anode, resulting in complete cessation of myocardial stimulation and absence of an electrocardiographic pacemaker artifact. Methods for avoiding this complication are proposed.


Normally functioning inhibited pacemaker concomitant with vertebral nerve stimulator. Electromagnetic inference is a recognized difficulty in concomitant cardiac pacing and nerve stimulation. A case is reported in which a vertebral nerve stimulator was implanted, with a transmitter antenna distal to the right nipple. Six months later, intermittent S-A block with Adams-Stokes attacks urgently necessitated cardiac pacing. The ECG lead II showed nerve stimulator potentials of 0.75 mV. Intracardiac electrogram with unipolar electrode registered potential of 0.25 mV, but with a bipolar system no such potentials were observed. A bipolar pacing electrode was therefore implanted, with an interference from the nerve stiumluator. Various aspects of interference are discussed.


Aggression in humans correlates with cerebrospinal fluid amine metabolites. Cerebrospinal fluid of the major central metabolites of serotonin (5HT), norepinephrine (NE), and dopamine (DA)--5-hydroxyindoleacetic acid (5HIAA), 3-methoxy-4-hydroxy=phenylglycol (MHPG), and homovanillic acid (HVA), respectively--were studied in a group of 26 age-similar military men with no history of major psychiatric illness, but with various personality disorders and difficulties adjusting to military life. Independently scored history of aggressive behavior showed a significant negative correlation with 5HIAA (r = -0.78) and a significant positive correlation with MHPG (r = 0.64).


Central serotonin metabolism and frequency of depression. Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement is based on two observations. First, in a majority of patients, the 5-HT disturbances persist after depression has abated. Secondly, 5-hydroxytryptophan seems to have prophylactic value, in particular in patients with persistent abnormalities in central 5-HT metabolism. In this study we approached the hypothesis that 5-HT disturbances are a predisposing factor to the occurrence of depression from still another perspective. If this hypothesis is correct, then depressive patients with persistent 5-HT disturbances should have higher frequencies of depression than depressive patients without demonstrable 5-HT disturbances. This was indeed demonstrated. The same was true for family members of probands with low levels of 5-hydroxyindoleacetic acid. No cerebrospinal fluid data are available for family members. The reported findings strongly support the predisposition hypothesis.


The mortality and birth rates of spina bifida during a period of treatment, selection and antenatal screening in Sheffield, 1963-1978. The birth rates for all neural tube defects and the mortality rates from spina bifida and encephalocele have been obtained for Sheffield children by examining the congenital anomalies register and death certificates during the period from 1963-1978. The introduction of atenatal alpha foetoprotein screening of all pregnant women in 1977 is associated in time with a sharp fall in the birth rate of neural tube defects. The mortality rate for spina bifida with encephalocele rose gradually from 1967 to 1976, apparently unaffected by the introduction of clinical selection prior to surgery in 1971. The antenatal screening of previously affected families (since 1973) did not affect the mortality rate, but screening the total pregnant population since 1977 has been associated with a sharp reduction in the mortality rate. The mortality rate curve for spina bifida with encephalocele is markedly different from the birth rate curve which makes the common practice of inferring birth rates from mortality rates invalid. There was a gradual increase from 1967 to 1978 in the proportion of children born with spina bifida in any given year who died before their second birthday. This increase appears to have been uninfluenced by the introduction of selection or antenatal screening. The changes in mortality rate and survival may be as much due to unknown factors as to changes in medical management.


Joseph E. Smadel Memorial Lecture: neuroimmunologic diseases of animals and humans. New precepts gained from the crescendo of neuroimmunobiologic research of recent decades have increased our understanding of experimental allergic encephalomyelitis (EAE), virus-associated acute disseminated encephalomyelitis (ADE), and multiple sclerosis (MS). EAE of animals and humans provides evidence of the existence in mammalian lymphoid tissues of potential clones of cells with autoreactivity for myelin basic protein (MBP) and other antigenic constituents of the central nervous system (CNS). In a new hamster model, EAE has been strikingly potentiated by persistent infection of the CNS with defective measles virus, a finding that also has implications for virus-associated ADE. Endogenous MBP or MBP degradation fragments, reactive with MBP antibodies of various affinities, have been detected by a recently devised radioimmunoassay in serum, plasma, and other body fluids of normal rats, rats with EAE, and patients with virus-associated ADE or MS. Circulating MBP or MBP fragments may be of great importance in inhibiting neuroautoimmune reactivity and play a role in repair of immunologic CNS injury should it inadvertently occur. Finally, the impressive degree of concordance of immunologic events in EAE, virus-associated ADE, and MS provides additional support for the central importance of host neuroimmunologic responses in the pathogenesis of these neutologic diseases.


[Urodynamic studies on normal bladders and bladders in metabolic disorders using diabetes mellitus as an example]. In various diseases of the kidney and the urinary bladder, in disturbances of potency and diseases of the outer genital the diabetes mellitus play an essential role. It was the aim the present investigations to establish with the help of manometric examinations of the urinary bladder in diabetics as well as in a comparative group which had no disturbed metabolism in what extent there exist objectively provable differences of the parameters chosen by us. From the results is to be stated that in diabetics, despite a slight increase of the capacity of the urinary bladder, a significant increase of the sphincter opening pressure and of the voluntary tonus of the sphincter is present. We explain these changes as an expression of a beginning disturbance of the innervation of the urinary bladder. In males of this age group from this result disturbances of miction which may lead to incorrect judgments, particularly in connection with a prostatic adenoma.


Activation of fungal alpha-amylase by dithioerythritol. The activity of fungal alpha-amylase has been shown to be influenced by disulfide-reducing reagents. Thus, the enzymatic activity increases in the presence of dithioerythritol or 2-mercaptoethanol. L-Cysteine is also capable of increasing the activity, but the activation competes with an inactivation reaction which dominates at higher reagent concentrations (greater than 20 mM). A possible scheme interpreting the results is given.


An efficient procedure for serial nucleic acid hybridizations by titration analysis. A simplified and efficient procedure has been developed for performing hybridization reactions and analyses of the percentage of hybridization on glass plates. This method is as accurate as conventional methods, while considerably reducing the time and costs to perform the hybridization in titration hybridization experiments.


[Morphological changes in the pineal body of domestic swine (Sus scrofa domesticus) depending on light]. The cerebral epiphysis of twelve gilts, aged 6.5 months, was histologically, histochemically, and histometrically tested, after the animals had been kept permanently under artificial light, 100 lux, or in darkness, interrupted twice a day by two hours of lighting, over ten weeks altogether. The parenchymal cells of the epiphyses of the animals kept in darkness changed clearly from those of the other group with constant exposure to light. Changes in the darkness animals included significant enlargement of the cell nuclear volume by 33 per cent, increase in nucleoli count as well as increases of lipids and ribonucleic acid in cytoplasm.


Theoretical basis for interest in acetylprocainamide and clinical experiences with this new antiarrhythmic agent. In conclusion, it was the differential responses of slow and rapid acetylators to procainamide therapy that gave the initial clues that acetylprocainamide might be a safer drug than procainamide. So far, the experience with acetylprocainamide has been encouraging.


Determination of small differences in buoyant density of macromolecules by analytical density gradient equilibrium centrifugation. A sensitive method is proposed for the determination of small differences between the buoyant densities of different species of monodisperse macromolecules by analytical density gradient equilibrium centrifugation. The procedure involves the measurement at sedimentation equilibrium of the bandwidths of the concentration distribution of the separate macromolecules and of a mixture of the different species. The difference in buoyant densities can then be estimated from the difference between the bandwidths.


Chromatographic properties of Sephacryl S-300 Superfine. Sephacryl S-300 Superfine is a new gel filtration medium that consists of allyldextran crosslinked with N,N'-methylenebisacrylamide. It was shown to have a separation range for proteins that extends to 1--2 x 10(6) dalton. The gel filtration properties were characterized by fractionation of human serum and of bovine colostrum. Thyroglobulin from pig could be isolated in one step in a very pure form. The flow properties were characterized by the relationship between flow rate and pressure drop. It was shown that Sephacryl has very good flow properties in comparison with Sephadex G-200 and that it can be used in large-scale columns.


Spectral properties of atrial and ventricular endocardial signals. The spectral energy distributions of signals picked up by endocardial, atrial and ventricular electrodes have been investigated. The results show similar spectral distributions for P-waves and QRS-complexes with maximum spectral densities at frequencies between 10 and 30 Hz.


Analysis of anti-sperm sera for T/t locus-specific antibody. An objective antiglobulin radioimmunoassay for the analysis of anti-spermatozoa antisera has been used to characterize more than 30 alloantisera. Each of these antisera was raised against spermatozoa from mice carrying T/t regin mutations. Whilst all of the antisera had considerable activity for mouse spermatozoa, none of them was found to contain antibodies specific for T/t region gene products. A detailed analysis of a single serum revealed that its activity is for antigens which are non-polymorphic, sperm-specific and species-specific. The failure in this study to detect antibodies specific for T/t region gene products is discussed.


Mode of operation induced by rapid external chest wall stimulation in patients with normally functioning QRS-inhibited (VVI) pacemakers. The effects of rapid external chest wall stimulation were evaluated in 10 patients with normally-operating unipolar, lithium-powered, QRS-inhibited pacemakers functioning in their control VVI (QRS-inhibited) mode. Stimuli delivered at slow rates resulted in the expected pacemaker inhibition. On the other hand, during rapid (greater than 900/min) external chest wall stimulation, 8 pacemakers reverted to a VOO mode, 1 to a VVI mode and 1 to either a VVI or VOO mode. No pacemaker was totally inhibited by rapid chest wall stimulation. In accordance with the manufacturer's specifications, the rate to which the implanted pacemakers reverted during the VOO modes produced by the fast external stimuli were the same as those of the VOO modes induced by proper application of an external magnet. Although rapid external chest wall stimulation proved to be a safe procedure, more studies are necessary to determine its usefulness in the follow-up of patients with implanted QRS-inhibited (VVI) pacemakers. At present, conclusions cannot be drawn regarding whether these pacemakers will revert to a mode of operation similar to that induced by rapid external chest wall stimulation when subjected to extrinsic sources of strong electromagnetic interference.


A microcomputer-based stimulator for clinical and experimental investigations in cardiac electrophysiology. A cardiac stimulator is described which combines the ease of operation required in clinical investigations, particularly endocavitary studies of cardiac arrhythmias, and the versatility needed in a research context. This instrument uses a microcomputer to control two independent optically-isolated stimulation ports which can be addressed either independently or jointly to stimulate at two different sites. The main software module operates as a cascade of ten real time pulse generators with individually presettable parameters: amplitude, duration, period, initial delay, periodic and cyclic modifiers, triggering mode, etc. A simple interactive procedure allows the operator to define a stimulation protocol either by accessing the generator structure directly, or by calling any of five pre-programmed stimulation protocols. With this combination, the instrument can provide a large variety of pulse patterns. The operator can intervene at any time during stimulation to change parameter values or modify the pulse pattern. Concurrently with stimulation, the instrument generates time-codes to help relate cardiac responses recorded on paper chart and magnetic tape, and reference them to specific events. The instrument can be readily expanded by the addition of parallel microprocessor modules; other real time tasks such as acquisition and processing of cardiac responses can thus be incorporated.


Permanent programmable pacemakers in the management of recurrent tachycardias. Patient reports are presented to indicate the application of standard implanted programmable pacemakers with endocardial electrodes for long-term overdrive suppression of recurrent ventricular tachycardia, and their adaptability to non-invasively induced burts of rapid ventricular pacing to cardiovert that arrhythmia. In carefully preselected patients with bradycardia-tachycardia syndrome, this type of programmable pacemaker may also be used to convert paroxysmal supraventricular tachycardia by short bursts of rapid ventricular pacing. In addition, the advantage of non-invasively instituting overdrive suppression with programmable pacemakers to control recurrent ventricular tachycardia appearing in patients being chronically paced for complete heart block is illustrated.


The porous endocardial electrode.

The porous endocardial electrode. The permanent endocardial electrode has exhibited the problems of dislodgement, excessive threshold rises and loss of sensing. These failure modes are addressed with a new electrode incorporating a porous body of Pt-Ir fibers with a fiber diameter of 20 micrometers and an overall density of 10%. Porous electrodes have the advantages of utilizing the electrode interior both for tissue ingrowth to improve anchoring and for electrolyte penetration which improves R wave amplitude and reduces polarization losses. A series of 20 porous electrodes was compared with 17 solid electrodes of similar dimension. Electrodes were implanted in dogs in the apex of the right ventricle, and were subsequently followed up to 210 days. Comparison of the electrode data revealed that the porous electrodes had a 40% reduction in chronic voltage thresholds and had an overall dislodgement rate of 10%, compared to 53% for the solid electrodes. Histological examination revealed tissue ingrowth throughout the electrode interior and a fibrotic capsule about half the thickness of the solid electrodes. R wave stability was enhanced with the porous electrode due to improved anchoring, reduction in slew rate changes and less R wave attenuation. Assuming results are translatable to humans, the porous electrode will provide a greater pacing safety margin when used with a standard demand pacemaker, or improved longevity with the same safety margin as solid electrodes if used with a programmable pacemaker. The incidence of dislodgement and sensing failure will also be diminished with the porous electrode.


Pacing failure due to an unusual fracture of the sutureless myocardial electrode. A 64-year-old man, had an apicardial demand pacemaker implanted for treatment of Mobitz type II heart block. Two sutureless myocardial electrodes were inserted, but a unipolar system was used based on stimulation threshold and sensitivity measurements. Fourteen months later the patient presented with pacing failure caused by a fracture of the corkscrew electrode with wide separation of the broken ends. The pacemaker, however, continued to inhibit satisfactorily. Pacing was successfully reestablished employing the second available lead. To our knowledge, there has been no publication reporting this type of failure of the sutureless myocardial electrode.


The recessed chest wall pacemaker pocket. Recurrent pouch problems led to the development of a recessed chest wall pacemaker pocket. Segments of the seventh and eighth ribs were resected in the mid-axillary line resulting in a "tailor-made" space suitable for generator implantation. Follow-up at one year has proven the chest wall to be a satisfactory alternative site for a pacemaker pocket.


The autodiagnostic pacemaker.

The autodiagnostic pacemaker. Loss of normal pacemaker stimulation and/or sensing functions requires prompt detection, automatic correction, and automatic and continuous "marking" of the intermittent failure. The autodiagnostic pacemaker (ADP) detects "failure to capture" (FC) by distinguishing, at its single stimulating and sensing electrode, between the normal biphasic cardiac response evoked by an adequate stimulus (corresponding to the QRS and T waves on the surface cardiogram) and the monophasic pseudo-response generated by electrotonic spread of a subthreshold stimulating current. Detection of "failure to sense" (FS) spontaneous cardiac activity requires two amplifiers: a "timing control" amplifier of standard fidelity and standard (approximately 250 ms) refractory period, and a second amplifier which has negligible refractoriness and provides high fidelity amplification of all evoked and spontaneous activity. Failure to sense (FS) is defined as a specified number of consecutive failures to recycle correctly the pacemaker's timing circuits. Similarly, a specified number of consecutive failures of the stimulus to evoke an active cardiac response is defined as a failure to capture (FC). When FC is detected, the ADP doubles the applied stimulus voltage and generates marker pulses which follow every subsequent stimulus by 40 ms. The marker pulses appear on the surface electrocardiogram, serving as an externally detectable "memory" of the earlier, possible corrected, failure. When FS is detected, non-stimulating marker pulses, of a different time relation (80 ms delay) to each stimulus, are generated continually and can also be detected externally. The ADP has been tested in 14 anesthetized, open-chest dogs. Unipolar rather than bipolar electrodes were used as they rpovided more reliable stimulation and more satisfactory electrograms for detection.


Chest thump and ventricular tachycardia. Chest thump is a simple method of treatment of some paraxysmal arrhythmias. Its therapeutic efficacy, electrophysiological bases and clinical utility have been studied in 17 patients during 45 episodes of ventricular tachycardia (VT). Thumping the precordium interrupted the VT in 22 episodes. Three types of interruption of VT have been observed: (1) In 15 episodes, single ventricular premature beats induced by the blow, occurring randomly in the cycle, stopped the arrhythmia; (2) In 5 episodes, a run of premature beats, induced by a rapid succession of blows, interrupted the tachycardia; (3) In 2 episodes, chest thump caused a short period of asystole followed by sinus rhythm. Chest thump is an antiarrhythmic treatment of definite clinical utility. The complications are rare, although there is a possibility of ventricular fibrillation. Therefore, it should be performed only under careful supervision.


Electrograms from the coronary sinus in acute myocardial infarction: implications for electrocardiographic guidance of pacing catheters. Intracardiac electrocardiography has been reported to be the most reliable of the techniques used for guiding placement of transvenous pacing catheters. When a catheter electrode is in contact with the right ventricular apical endocardium, the intracardiac electrogram demonstrates marked ST segment elevation and, usually, a very large S wave. The case presented indicates that both of these features of the intracardiac electrogram should be sought since ST segment elevation alone may represent epicardial recording of an acute myocardial infarction when the catheter electrode is in the coronary venous system.


Dual-demand pacing for refractory atrioventricular re-entry tachycardia. An automatic dual-demand pacemaker has been used in six patients to treat refractory attacks of paroxysmal re-entry atrioventricular tachycardia that occurred in the Wolff-Parkinson-White syndrome. The pacemaker was designed to pace at a fixed rate of 70 beats per minute when sensed heart rates were either below this rate or above 150 beats per minute; in the latter case, it would compete with the paroxysmal tachycardia and interrupt it after a short period of random scaning. The best location for the permanent pacing electrode and the feasibility of using the pacemaker were tested in each case during a detailed preliminary intracardiac electrophysiological study. The permanent pacing electrode was positioned in the coronary sinus in three patients and was attached to the epicardium of either the left or right ventricle in another three. All patients were given regular oral doses of verapamil or propranolol to enhance the effectiveness of the pacemaker system and, with the latter, to prevent pacemaker activation during sinus tachycardia. Over a follow-up period of between 11 and 47 months, the pacemaker system remained completely effective in three patients, but developed unreliable sensing in another two (one coronary sinus and one left ventricular lead). In the sixth patient the pacemaker was only effective when the rate of the tachycardia remained below 170 beats a minute, as when she was resting supine; when sitting or standing, however, her tachycardia rate considerably exceeded this value and the pacemaker was ineffective. Explantation of the pacemaker and either successful cryosurgical ablation of the accesory AV pathway or treatment with amiodarone was undertaken in the three patients in whom the pacemaker had failed.


"Runaway" in a modern generation pacemaker. Life-threatening episodes of ventricular tachycardia were documented in a patient with an implanted Omni-Stanicor pacemaker due to episodic pacemaker runaway. The unit generated impulses at rates varying from 73 to 500 per minute. Ventricular capture at high rates was variable, but frequently resulted in heart rates in excess of 200 per minute. These episodes were associated with loss of consciousness secondary to inadequate cardiac output. Although the pacemaker could be inactivated by reprogramming its output to 2 mA, and suppressed by chest wall stimulation with an external pulse generator, no spontaneous rhythm resulted during these maneuvers. Urgent removal of the battery at the bedside and immediate resumption of pacing with an external generator was required to resolve the problem. Although runaway is infrequent with current generation pacemakers, it should be considered in addition to the more common causes of pacemaker malfunction in the patient with appropriate symptoms.


Pre-P (Sino-atrial node region) activity recording from the right atrial cavity by signal averaging. A mobile instrumentation and noninvasive method developed recently for external His bundle recording and employing the signal averaging technique was applied for intra-atrial recording of the pre-P (sino-atrial node region) activity. Recordings were obtained in ten anesthetized dogs and five patients at the time of right heart catheterization. A bipolar intra-atrial lead was used for triggering of the averaging process and a unipolar intra-atrial lead was used for signal recording. Direct bipolar epicardial recordings were obtained for comparison from the sino-atrial (S-A) node area in experimental animals. In animals studies, the averaged intra-atrial recording showed 30 muV amplitude deflections beginning 40-45 ms prior to the onset of P wave and were preceded by a slow rise and lower frequency and amplitude deflections arising 60-70 ms earlier. There was good correlation between the pre-P activity recorded intra-atrially and from the epicardium. Deflections of similar configuration but smaller amplitude (1 muV) were recorded in human studies. They preceded the onset of large atrial activity deflections (P wave) in the reference electrocardiogram by 40-80 ms. The exact source of these pre-P activity potentials has not been definitely established, but they appear to originate from the S-A node region, based on their similarity to the direct epicardial recordings and time relationship to the preceding T and following P wave.


Temporary pacemaker treatment in open heart surgery: variation in myocardial threshold, tissue and interface impedances in man. Myocardial threshold and impedance of adequately insulated multicore metal electrodes (lengths l1 and l2) were investigated in 28 patients undergoing open heart surgery. Increase in current threshold from the pre-to postoperative period was: 607 +/- 102% (mean +/- SEM) with a constant-current pulse generator and 885 +/- 129% with a constant-voltage pulse generator. Tissue impedance (RT - initial impendance) calculated as voltage/current ratio 90 mus into the pulse changed from 564 +/- 34 omega before surgery to a minimum of 134 +/- 7 omega. Thereafter, there was a gradual increase in RT to 162 +/- 9 omega the day of electrode removal. In 25 of 28 patients the minimum values were reached the third to eighth postoperative day. Electrode/tissue interface impedances--Faraday resistance (RF) and Helmholtz capacity (CH)--were calculated from regression analysis of loaded and unloaded electrograms using the method of least squares. The RF showed a fall from 14.7 +/- 1.4 K omega to 5.2 +/- 0.3 K omega, and the CH (20-40 Hz) rose from 6.0 +/- 0.9 mu F to 15.5 +/- 0.8 muF preoperatively to the day of minimum tissue impedance. There were no further changes until the day of electrode removal. A significant positive correlation was found between CH (p < 0.002), current threshold (p < 0.005) and equivalent electrode length [lequ = l1 X l2/(l1 + l2)]. The electrode signal source impedance calculated from RT, RF and CH was of a magnitude not likely to contribute to demand failures. The low postoperative electrode impendance resulted in excessive load on the constant-voltage generator (condenser discharge type), rendering stimulation of the heart with reasonable current values impossible.


Long-term results of permanent atrioventricular sequential demand pacing. Pervenous atrioventricular sequential demand pacemakers (AVSDPs) were implanted in 18 patients using an atrial electrode positioned in the right atrial appendage and a ventricular electrode positioned at the apex of the right ventricle. The indications included 13 patients with the sick sinus syndrome (72%), five of whom had the tachycardia-bradycardia syndrome, three with paroxysmal supraventricular tachycardia, one with cardiomyopathy and one with carotid sinus syncope. The follow-up ranged from 6 to 38 months, with a mean of 19.4 months (a total of 350 pacing months). Seventeen patients (94%) are asymptomatic. One patient had persistent episodes of paroxysmal supraventricular tachycardia. In the remaining patients with tachyarrhythmia, pacing alone (three patients) or in combination with antiarrhythmic drugs (four patients) controlled the tachyarrhythmia. There was one displacement of the atrial electrode (5.5%). Extrusion of the pacer occurred in three patients. It is concluded from this experience that AV sequential pacing is an effective technique and may be useful in patients with sick sinus syndrome, in patients with tachyarrhythmia and/or patients with poor myocardial function. However, continued research is needed to prolong battery life and to reduce the size of the pacemaker.


Gas pocket causing pacemaker malfunction. Pacemaker malfunction was attributed to the increase in impedance to current flow caused by a pocket of air separating the anodal contact plate of a unipolar generator from the overlying skin. Lack of capture was noted 20 hours after implantation. The malfunction was permanently corrected by bedside aspiration of the gas with a sterile syringe.


Pitfalls in measuring R waves in pacemaker-dependent patients. Determination of adequate R wave sensing is an important step in pacemaker electrode implantation and pacemaker replacement operations. In patients who are completely pacemaker dependent, these operations are usually performed with a functional temporary pacemaker in place throughout the testing period. In such patients, there is the special problem of determining whether the test system is sensing the temporary pacemaker spike rather than the resultant QRS voltage. Patients were studied and a laboratory model was created to evaluate the response characteristics of a standard R wave test device. Patients showed two general types of curves as R waves were measured at various output voltages of the temporary pacemaker. Type A responses showed direct correlation between output voltage and measured R waves. Type B responses showed an initial high plateau of R waves followed by an abrupt fall below acceptable values, and then a direct correlation between R waves and output voltage. Laboratory testing revealed that the temporary pacemaker spike, and not the R wave, was being "sensed" in Type A curves, and that the R wave was sensed only in the initial plateau of the Type B curves. This pitfall can lead to acceptance of an unsatisfactory electode position in some patients and to futile electrode repositioning in others.


Suppression of an external demand pacemaker by diaphragmatic myopotentials: a sign of electrode perforation? Transient pacemaker inhibition was observed in a patient with an external bipolar demand pulse generator. Recordings of the proximal, distal and bipolar electrograms showed extracardiac myopotentials only in the unipolar distal and bipolar configuration. These myopotentials which caused inhibition of the pulse generator were related to respiration and other maneuvers that resulted in active contraction of the diaphragm, thus proving their diaphragmatic origin.


Recurrent pulmonary emboli secondary to right atrial thrombus around a permanent pacing catheter: a case report and review of the literature. This report describes the management of a woman with multiple pulmonary emboli secondary to a large right atrial clot which had formed around her permanent transvenous pacemaker. She continued to have pulmonary emboli despite adequate anticoagulation. Removal of the catheter and pacing required right atriotomy under cover of cardiopulmonary bypass. Additionally, eight English language case reports of symptomatic pericatheter thromboses are reviewed. In these cases, pericatheter clot resulted either in right-sided inlet obstruction or pulmonary emboli. The mortality rate was 75%. Although the cause for our patent's thromboembolic events is uncertain, congestive heart failure was a predisposing factor in 75% of the other reported cases. We suggest that pacemaker patients in congestive heart failure might benefit greatly from chronic anticoagulation.


Ventricular pacing from the middle cardiac vein mimicking supraventricular morphology. A case is described in which ventricular pacing from the middle cardiac vein produced an electrocardiographic pattern which mimicked the morphology of the normally conducted beats. The possible etiologies of this unusual phenomenon and its implications concerning the functional anatomy of the normal conduction system in the human heart are discussed.


Diagnostic implications of atrial vulnerability. Extrastimulation in the atrial vulnerable zone may result in atrial fibrillation or flutter (AFF), especially with stimulation of multiple atrial sites. However, the clinical relevance of such vulnerability to AFF is unknown. Therefore, single twice-threshold extrastimuli were applied at three disparate right atrial sites in 45 consecutive unmedicated patients without overt heart failure. Group I consisted of 12 patients with documented spontaneous paroxysms of AFF. AFF was duplicated in 9 to 12 patients using extrastimulation in the vulnerable zone (5 in sinus rhythm, 4 requiring atrial pacing at 120 beats/min). Group II consisted of 33 patients without documented AFF dispite monitoring. Vulnerability to AFF was found in 12 of 33 patients (4 in sinus rhythm, 8 requiring atrial pacing). The duration of induced AFF did not discriminate between the two groups. Among the 12 Group II patients vulnerable to AFF, 3 had rapid palpitations, 2 had undiagnosed rapid tachycardias, 1 had atrial tachycardias and 1 junctional tachycardias. In vulnerable patients, the pause after AFF correlated with the pause after atrial pacing, but only 1 of 11 Group II patients with sick sinus syndrome was vulnerable. Thus, paroxysmal AFF may be duplicated with the extrastimulus technique if sufficient arial sites are stimulated, providing a model for evaluation of these arrhythmias. But atrial vulnerability, even to extrastimulation at normal heart rates, may be seen in patients suspected of atrial tachyarrhythmia in the absence of documented AFF, and does not contribute to the diagnosis of sinoatrial dysfunction.


Unusual demand pacemaker arrhythmia due to partial recycling in the relative refractory period. This report presents the electrocardiograms of a patient with a normally functioning lithium QRS-inhibited pulse generator that exhibited partial recycling with inappropriately short escape intervals. The occurrence of partial recycling was time-dependent rather than voltage-dependent, and was observed only when QRS complexes fell within the relative refractory period of the pulse generator. This resulted in a complex arrhythmia simulating pulse generator malfunction. This observation re-emphasizes the need for the physician to appreciate the technical characteristics of pulse generators to avoid the unnecessary replacement of normally functioning units.


Spontaneous termination of reentry ventricular tachycardia in the late myocardial infarction period: an experimental study in the dog. Forty episodes of induced ventricular tachycardia in the late myocardial infarction period (4-6 days old) were analyzed in 12 dogs in an attempt to identify the possible mechanisms for the termination of reentry tachycardia. Multiple epicardial and endocardial composite electrograms were recorded in and around the central ischemic zone of the infarction. During tachycardia, the earliest site of activation was identified in the epicardial surface of the border or normal zone immediately adjacent to the ischemic zone in 36 of the 40 episodes, suggesting efferent epicardial spread from the site of the activity. In four instances, the efferent pathways were directed to the endocardial surface. Four distinct patterns of activation sequences were observed during spontaneous termination: (a) a shift of the efferent pathways from epicardial to endocardial site (19 instances); (b) a change of the efferent pathways within the endocardium (4 instances); (c) a shift of the earliest site of activation between the left and right ventricles (9 instances); and (d) no apparent change in the epicardial efferent pathways (4 instances). In four other instances, ventricular tachycardia deteriorated into ventricular fibrillation. In patterns (a) and (c), a shift of the efferent pathways resulted in a more rapid and homogeneous activation of the border and normal zone epicardium. These changes were associated with cessation of delayed or continuous activity in the ischemic zone epicardium, resulting in termination of tachycardia.


The optimization of the pulse delivered by the pacemaker. The results of stimulation threshold analysis carried out in 230 patients after the initial electrode implantation, and in 188 patients during pacemaker replacement, are presented. The electrodes investigated were the IE-60K-10 (279 cases), the IE-60-K (96 cases) and the ME-50 (26 cases). The chronic stimulation threshold voltage for the electrode IE-60K-10 (electrode surface area: 10 mm2) at a pulse width of 0.5 ms, after an electrode function time of 25 months, is 2.05 +/- 0.18 V, representing 256% of the acute threshold, and is equally as high as the chronic figure for the IE-60-K electrode (surface area: 27 mm2) measured at 2.08 +/- 0.20 V. The current threshold for the IE-60K-10 increased from 0.78 +/- 0.07 mA by 299% to 2.33 +/- 0.30 mA and was thus, as expected, lower than that of the large area electrode IE-60-K, which increased from 1.11 +/- 0.22 mA to 3.23 +/- 0.43 mA (291%). On the basis of the computation of the stimulation threshold energy and the stimulation threshold charge, a reduction of pulse duration to below 0.5 ms would not appear to make such energy-saving sense.


Automatic "scanning" by radiofrequency in the long-term electrical treatment of arrhythmias. The use of programmed electrical stimulation in the long term treatment of re-entry tachycardia offers encouraging perspectives. Among the others proposed, the "scanning" system seems to be the most effective. However, an implantable stimulator with these features is not yet available and, thus, a temporary external lead is required. These difficulties have been overcome by utilizing radiofrequency to synchronize and stimulate. An implantable device was therefore designed which is triggered by the patient and automatically searches the interruption zone of the tachycardia by exploring the R-R cycle. The external transmitter, which can produce one or two synchronized impulses, is programmed to scan the R-R cycle with progressive steps of 5 or 10 ms; when tachycardia is interrupted, further stimulation is inhibited. The implanted module connected to an endocavitary lead does not have any power supply and, therefore, is very small. The efficacy of this method has been demonstrated in 4 patients with supraventricular tachycardia (3 with WPW syndrome) resistant to conventional pharmacologic therapy.


Beat-to-beat stability of implanted pacemakers. A method of measuring and analyzing beat-to-beat interval stability of implanted pacemakers has been devised, and a number of normal and failing pacers have been studied in this way. It was seen that normal pacer rates were remarkably stable, but that abnormalities in beat-to-beat interval were found in 67.4% of all failing pacers. The abnormalities consisted primarily of excessive interval (rate) scatter, linear and cyclic fluctuation, and transients following application of a magnet. It is expected that in problem cases a beat-to-beat analysis will be of help in differentiating normal from abnormal pacer function, and will provide confirmation signs of pacer failure; it may also uncover unusual and heretofore unpredictable failure modes.


Symptomatic sinus node disease: natural history after permanent ventricular pacing. Fifty-nine patients between the ages of 13 and 88 with sinus node disease, who received a permanent ventricular pacemaker between 1965 and 1976 at one institution, were followed to determine the natural history of the disorder after permanent pacing. Nineteen had ischemic heart disease, six had primary myocardial disease, and eight valvular heart disease. In 26, no etiology for the arrhythmia was apparent. The one- and five-year survival was 85.5% and 73.1%, respectively. Patients with underlying heart disease had a significantly poorer survival when compared to those without (58% versus 94% at 36 months) and all but 3 of 13 deaths in the first 36 months were in those with ischemic heart disease. There was a distinct trend toward poor survival in those with heart failure prior to pacemaker implant and those over age 65. Patients with sinus bradycardia alone did best (91% survival three years after implant), while those with bradycardia-tachycardia syndrome and those with sinoatrial arrest alone did distinctly worse (76% and 65% survival at three years, respectively). Twelve of 18 deaths were due to progression of underlying heart disease. The long-term prognosis with symptomatic sinus node disease can be predicted in part by (1) etiology of the underlying heart disease, (2) pre-implant arrhythmia, and (3) ventricular function prior to implant.


Instrumentation for the follow-up of pacemade patients. Telephone transmission of the electrocardiogram and self-check by the patient on pacemaker function and capture. Logic circuitry has been added to an electrocardiogram telephone transmitter. It processes the electrocardiogram and permits frequent self-checks by the patient on rate, capture and sensing function of an implanted demand pulse generator system. Correct function is communicated to the patient by a green light. Malfunction with regard to any of these parameters produces an irreversible yellow light signaling the patient to contact his physician. The self-check is reassuring to the patient during intervals between visits to the physician's office or a specialized clinic. The system, at present, is applicable only to demand pulse generators with a high magnet test rate (90 ppm or higher) which assures capture in virtually all patients. This and other limitations are discussed. Their incidence is low, some can be remedied and in the majority of patients they do not impair the clinical usefulness of the system.


Sick sinus syndrome and AV node re-entry. A 69-year-old man presented with recurrent palpitations since childhood. Electrophysiology studies performed on two separate occasions revealed the combination of sick sinus syndrome and AV node re-entrant tachycardia. The case is reported because it illustrates marked temporal variability in the electrophysiological properties of the dual AV node pathways, and also deleterious effects of verapamil on sinoatrial node function.


Permanent rapid atrial pacing to control supraventricular tachycardia. A case is reported of a patient who had continuous supraventricular tachycardia with a ventricular rate of about 170. The arrhythmia was refractory to drugs and DC countershock, and did not convert with atrial pacing. Rapid atrial stimulation controlled the ventricular rate by simulating atrial fibrillation (pacing at 300-400/min), or by simulating a faster atrial tachycardia with 2:1 conduction (pacing at 205-210/min). This form of therapy was used on a permanent basis for more than five months.


Inappropriate slowing of the pacemaker rate with programmable demand pacemaker. A 60-year-old male with a programmable pacemaker developed inappropriate slowing of the pacemaker rate. This was due to oversensing of the T waves combined with after-potential sensing. This does not represent generator malfunction and can usually be corrected by reprogramming the pulse duration, or the milliamperage.


Intravenous disopyramide phosphate and ventricular overdrive pacing in the termination of paroxysmal ventricular tachycardia. Both antiarrhythmic drugs and bursts of rapid ventricular pacing provide alternatives to DC cardioversion for the treatment of paroxysmal ventricular tachycardia. This report considers the individual and combined success of burst ventricular pacing and intravenous disopyramide phosphate in the tretment of 11 examples of paroxysmal ventricular tachycardia. Rapid ventricular pacing, at a rate of up to 50 beats/min faster than the tachycardia rate terminated 7 of the tachycardias. Intravenous disopyramide resulted in increased tachycardiac cycle length (342 +/- 34 ms-385 +/- 56 ms), increased QRS complex width (147 +/- 42 ms-180 +/- 41 ms) and termination of 8 the tachycardias. The remaining 3 tachycardias could be terminated by bursts of ventricular pacing following the infusion of disopyramide. Of these, 2 could not be terminated prior to disopyramide. The use of both techniques allowed the extinction of all 11 tachycardias and prevented the need to proceed to DC conversion.


Polarization properties of small-surface-area pacemaker electrodes--implications on reliability of sensing and pacing. The polarization characteristics of Pt-Ir and Elgiloy small-surface-area (10-12.5 mm2) pacemaker electrodes were studied at AC linear (sensing) and DC non-linear (pacing) conditions. The electrodes' AC polarization impedance was approximately equal to the demand pacemaker's input impedance, which causes waveform distortions ofthe sensed R-wave potentials. The pacemaker's coupling capacitor adds to the distortion's effect. As a result of amplitude attenuation (up to approximately 50%) and slew rate changes, the pacemaker may fail to recognize the ventricular complexes, reverting to hazardous competitive pacing. The impact of the DC polarization elements and of the coupling capacitor on the effectiveness of pacing was examined. The deficiency of small area electrodes was pointed out, this being counter-balanced to some extent by their lower pacing thresholds. The necessity to ensure a sufficient safety margin between the pacing pulse and the stimulation threshold, to avoid possible reasons for creation of exit blocks, was stressed. In reducing the electrode surface, it is advisable not to step down below a 15-20 mm2 effective area for Pt-Ir, and a 40-50 mm2 area for Elgiloy.


Comparison of active and passive adhering leads for endocardial pacing. The frequency of lead failure requiring invasive correction in a total of 276 implants of four different transvenous leads (6907, continuous lead, IE-65-I, and MIP 2000) was observed during a one-and-one-half year period with a minimum of two months follow-up post-implant. Implants were on a successive sequential basis, randomly distributed between the two surgeons normally performing implants, and unselected for presumed ease or difficulty of the procedure. Failure rates with the 6907 and continuous leads were 7 of 76, or 9.2%; with the IE-65-I, 2 of 76, or 2.6%; and with the MIP 2000, 8 of 45, or 17.8%. The difference between the IE-65-I and the two conventional leads was significant at the 5% level, and between the IE-65-I and the group of the other three at the 1.6% level. The MIP 2000 was significantly different from the other three leads at the 2.7% level. Previous clinical experience with 849 implants with continuous and 6807 leads indicated that the overall data was similar to that obtained in the present evaluation. No significant differences in failure rates between surgeons and no measurable "practice effect" could be detected. It was concluded that the design of the lead is a major factor in the differing need for early secondary intervention.


His bundle electrogram in patients with acute myocardial infarction. Thirty-seven patients with acute myocardial infarction complicated by atrioventricular or bundle branch block, or a combination of both, has His bundle electrogram studies performed during their stay in the coronary care unit. The acute mortality of the 14 patients with a complicating bundle branch was 50%. Pump failure was the main cause of death. Three patients in this group had a prolonged H-V interval and one patient had a split blundle of His. The presence or absence of a prolonged H-V interval did not affect mortality in this group of patients. The acute mortality of the 16 patients with an inferior wall myocardial infarction was 6%. The H-V interval was normal in all but one of these patients. The atrioventricular block was caused by a proximal block in all cases. The acute mortality of the seven patients with an anterior wall myocardial infarction was 29%. The H-V interval was prolonged in two of seven patients. Pump failure was the acute cause of the deaths. The presence or absence of a prolonged H-V interval did not affect mortality in this group of patients.


Adrenergaically mediated ventricular fibrillation in probucol-treated dogs: roles of alpha and beta adrenergic receptors. A high incidence of sudden death due to ventricular fibrillation (VF) has been observed in dogs under chronic treatment with probucol, a new hypocholesterolemic agent. The present study describes the cardiac electrophysiologic properties of probucol-treated dogs and characterizes the electrophysiological response of these animals to manipulation of the autonomic nervous system. There was no significant difference in the spontaneous sinus cycle length, the QT interval, refractory period of the atrium, ventricle or A-V junction between normal and probucol-treated dogs. Epinephrine produced VF with few and sometimes no preceding premature ventricular extrasystoles. Electrical stimulation of the stellate ganglion induced VF in 16/19 dogs whereas stimulation of the right stellate ganglion induced VF in 1/19 dogs. Phenylephrine induced VF in 0/19 dogs, isoproterenol in 5/19 dogs, but phenylephrine + isoproterenol induced VF in 9/11 dogs in which isoproterenol did not produce VF. alpha (phentolamine) or beta (propranolol) blockade prevented initiation of VF by epinephrine, phenylephrine + is isoproterenol, and left stellate stimulation but alpha blockade did not prevent induction of VF by isoproterenol when isoproterenol alone produced VF. In this nonischemic model, we conclude that left stellate stimulation is a far more potent initiator of VF than right stellate stimulation and that induction of VF appears to require both alpha and beta adrenergic receptor stimulation.


Preliminary experience with the helifix electrode for transvenous atrial implantation. A Helifix electrode was inserted transvenously in the right atrial appendage for temporary atrial stimulation in three patients. The low stimulation threshold as well as the excellent stability of the electrode encouraged us to proceed to permanent implantation of this lead in thirteen patients. The lead was introduced through the saphenous vein in twelve patients and through the cephalic vein in one patient. Five patients had sinoatrial dysfunction and five had bradycardia-tachycardia syndrome; they received atrial demand pacemakers. Two patients had atrioventricular block and received atrial synchronous ventricular pacemarkers. Our last patient had restrictive cardiomyopathy, heart failure and a drug-refractory atrial arrhythmia. She received a dual-chamber sequential pacing device. Atrial electrode displacement occurred in one patient soon after implantation. The lead was promptly repositioned without difficulty. Partial sensing of spontaneous P waves was observed in two patients. One recovered spontaneously, the second after substituting a pulse generator with a higher input sensitivity. Our clinical experience during the period from November 1977 to January 1979 has shown that the Helifix electrode is suitable for transvenous atrial implantation.


Escape rhythm in complete A-V block. The recovery phase after overdrive suppression from artificial ventricular suppression from artificial ventricular pacing. In 60 patients with third degree A-V block, recovery of escape rhythm from overdrive suppression after ventricular pacing has been studied. Implanted unipolar VVI pacemakers were inhibited by chest wall stimuli. A total of 165 rhythmograms were studied. In 37, the rate was irregular, in the other 128 the escape rate increased gradually, following an exponential curve until stabilization after 3 minutes. In 29 of these rhythmograms, a possible exit block of the first escape impulse was observed. In 99 rhythmograms without exit block, escape rhythm recovery time was an average 1.45 times basal escape RR intervals. Overdrive suppression was most marked in patients with a slow escape rhythm.


Complications of defibrillation with permanent pacemaker in situ. A permanent demand pacing generator was implanted in the right deltopectoral fossa with unipolar transvenous lead advanced to the right ventricle. Implant and subsequent pacing parameters were normal. Five days later an emergency DC cardioversion was performed with one paddle 2 inches from the generator. Cardioversion was followed by failure of QRS-sensing and, at immediate explant, rise in stimulation threshold. The pulse generator showed end-of-life characteristics. The patient died 4 days following replacement of the generator and lead. At autopsy, right ventricular infarction was found, presumably relating to current discharge along the lead. Pacemaker analysis showed damage to the protection zener diode and oscillator integrated circuit of the generator during cardioversion.