[The anti-androgen flutamide in the treatment of prostatic hyperplasia]. The authors treated 23 benign prostatic hyperplasia (BPH) patients with antiandrogen flutamide. Half of the patients were treated with 500 mg, the another part with 750 mg flutamide for three months, and after 3 months brake again for 3 months. The decrease of the residual urine and an increase of the flow were observed. The subjective parameters were improved, too. In some patients side effects (gynecomastia, loss of appetite and potency) were observed. There was no different in the effect of the two doses.


Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells. Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4).


Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. We have cloned and sequenced the human KIT proto-oncogene, which contains 21 exons and spans more than 34 kb of DNA on chromosome segment 4q12. We also establish physical linkage between the KIT gene and the related PDGFRA gene. The organization of the KIT gene is virtually identical to that of the homologous FMS gene, located on chromosome 5. Together, these data suggest that the KIT and PDGFRA genes on chromosome 4 and the FMS and PDGFRB genes on chromosome 5 arose by duplication of a common ancestral gene, followed by duplication of a chromosome.


Effect of substance P on ciliary beat frequency in human adenoid explants. This study investigated the direct effects of substance P (SP) on ciliary beat frequency of human upper airway mucosa. Human adenoid explant tissue was maintained in serum free culture media, MCDB153. Ciliated epithelial cells were observed with phase-contrast microscopy and ciliary activity was measured using a photometric technique. Oscillations in transmitted light caused by ciliary beating were recorded and modal ciliary beat frequency was determined by fast Fourier transformation. Specimens were treated with SP at concentrations of 10(-4), 10(-5), 10(-6), and 10(-7) mol/L and with equal molar solutions of SP and (D-Pro2,D-Trp7,9)-SP, a SP antagonist. Substance P was found to increase ciliary beat frequency in a dose-dependent manner with a maximum increase of 12.1%. This effect was not seen with solutions containing (D-Pro2,D-Trp7,9)-SP. This suggests that SP exerts a direct stimulatory effect on ciliated cells of the upper airway. Because SP is known to be released in the upper airway in response to chemical irritation, it is presumed that the stimulatory effect of SP on mucosal cells provides a protective mechanism against inhaled irritants.


Comparison of the vasoconstrictive and anesthetic effects of intranasally applied cocaine vs. xylometazoline/lidocaine solution. Cocaine solution has traditionally been the agent of choice for vasoconstriction and anesthesia when applied topically to the nasal mucosa during nasal operative procedures. Because of the relative scarcity and resulting expense of cocaine, there has arisen an impetus for an alternative intranasal solution for mucosal anesthesia and vasoconstriction. As a logical alternative, we have used a mixed solution of xylometazoline and lidocaine with reasonable results. No clinical studies comparing the efficacy of the two solutions exist, however, and there is presently no such solution commercially available. A double-blind, randomized, placebo-controlled study was undertaken to assess the relative efficacy of the preparations. Both solutions resulted in a marked and roughly equivalent degree of mucosal vasoconstriction (as evidenced by comparable increases in nasal airway cross-sectional area). Subjective pain ratings of mucosal pin-prick decreased a surprisingly small degree after application of both solutions. It appears that xylometazoline/lidocaine solution is comparable to cocaine solution for purposes of vasoconstriction and anesthesia during intranasal operative procedures.


Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization. Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.


Monoclonal antibodies recognize a processing dependent epitope present in the mature CS protein of various plasmodial species. In the present paper, we have characterized the specificity of a series of monoclonal antibodies (MoAbs) against Plasmodium berghei sporozoites, selected for their lack of reactivity with the repeat domain of the circumsporozoite (CS) protein. We found that these MoAbs recognize Pb44, the mature membrane form of the CS protein, but they do not react with Pb54, its precursor. Furthermore, these MoAbs do not react with any of the synthetic peptides representing the linear sequence of the P. berghei CS protein nor do they react with a recombinant CS (rCS) protein. These observations indicate that the epitope recognized by these antibodies is expressed only after the processing of the CS protein has occurred. This 'processing dependent epitope' is present in sporozoites of P. berghei, and also in those of P. falciparum, P. yoelii and P. brasilianum. It is not present in sporozoites of the P. cynomolgi-P. vivax complex and of P. gallinaceum. These anti-sporozoite MoAbs strongly inhibit sporozoite invasion of hepatoma cells, in vitro, however, they displayed no protective effect in an in vivo assay.


An evaluation of the role of carbohydrate epitopes in immunity to Trichinella spiralis. A study is described in which the role of carbohydrate epitopes in the generation of protective immunity to Trichinella spiralis was investigated. Antigen preparations were treated with increasing molar concentrations of sodium periodate, which is known to degrade carbohydrate moieties by cleaving one side of the hexose ring, and a suitable protocol was established for the selective degradation of carbohydrates with the retention of protein integrity. Using excretory/secretory (ES) proteins, both sodium periodate treated and in their native form, vaccination experiments have shown that sodium periodate treated antigens are as effective as native ES proteins in the generation of both active and passive immunity. This indicates that peptide epitopes alone can induce protective immunity to T. spiralis.


Development of a bleomycin hamster model of subchronic lung fibrosis. The existing bleomycin (BLM)-rodent model of lung fibrosis requires large doses and is often associated with morbidity and high mortality. We have developed an intratracheal multiple-dose BLM-hamster model of lung fibrosis. In this model, 3 consecutive doses of BLM (2.5 U, 2.0 U and 1.5 U/5mL/kg) were instilled intratracheally, one dose per week. The hamsters were killed at 10, 20, 30, 60 and 90 days after the last IT instillation and the lungs were lavaged or perfused with saline. This regimen of BLM administration was devoid of morbidity and caused only 6% overall mortality. Lung prolyl hydroxylase activity at 10 days and hydroxyproline content at 20, 30, 60 and 90 days were significantly higher than noted for the controls. Bronchoalveolar lavage fluid-supernatant protein and the total number of recovered cells of all types were significantly higher than observed for the controls at all times, except at 90 days. Lungs showed a multifocal mixed mononuclear infiltrate at 10 and 20 days and septal fibrosis, which was most severe and organized at 30 days and less severe at 60 and 90 days. The parenchymal lesions were significantly greater than those of the controls at all times, except at 10 days. This model, which required only 6 U BLM/kg, induced a moderate level of lung fibrosis. It has been concluded, therefore, that this model, inasmuch as it is not associated with an overwhelmingly acute inflammation, would be more applicable for screening potential antifibrotic agents than existing models of lung fibrosis.


Expression and regulation of L-selectin on eosinophils from human adults and neonates. L-Selectin, previously known as LEC.CAM-1, LECAM-1, LAM1, and as the MEL-14, Leu-8, TQ1, and DREG-56 antigens, is a leukocyte membrane protein that participates in adhesion to endothelium. We studied its expression on eosinophils using flow cytometry and the MAb Dreg-56 and Leu-8. Unstimulated peripheral blood eosinophils from healthy adults expressed about one third the level of L-selectin as neutrophils (mean +/- SD specific fluorescence: 20.9 +/- 3.2 versus 54.5 +/- 8.4, p = 0.0001, n = 18). After stimulation with A23187, L-selectin expression on eosinophils was rapidly lost. This was temporally correlated with increased expression of Mac-1 (CD11b/CD18); the kinetics on eosinophils and neutrophils were similar. Eosinophil expression of L-selectin decreased modestly after stimulation with platelet activating factor, but was minimally affected by N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4, or C5a compared with their effects on neutrophils. Eosinophils from cord blood of healthy neonates born at term expressed less L-selectin than adult eosinophils (10.4 +/- 3.8 versus 19.4 +/- 2.7, p = 0.0001, n = 9); the relative reduction was the same as on cord blood neutrophils (36.4 +/- 8.2 versus 55.5 +/- 4.8, p = 0.0001, n = 9). Relative to baseline expression, the responses of neonatal and adult cells to stimulation did not differ. We conclude that neonatal eosinophils have abnormalities in L-selectin expression similar to neonatal neutrophils and suggest that decreased expression of L-selectin and a diminished responsiveness to direct stimulation with chemotactic factors are possible mechanisms that may limit the exudation of eosinophils.


[Spheroidal deposits of amyloid in prolactin-secreting pituitary adenomas]. Nine peculiar cases of pituitary adenomas were pointed out by a retrospective investigation at the Ospedale di Legnano (from 1978 to 1984) and at the Ospedale di Circolo di Varese (from 1973 to 1986). These tumours are chromophobe adenomas with diffuse structure. Histologically they show typical, large, spheroid and concentric amyloid deposits, in addition to common, amorphous--often perivascular--ones. They were investigated by histochemical methods (Crystal-Violet, Congo-Red) and by immunohistochemical ones as well (anti-PRL and anti-GH), showing that these deposits are amyloid and are in close relation with PRL production. In particular, by immunohistochemical methods we found out that the cells of the tumours displaying spheroidal bodies do contain prolactin, not GH. The amyloid deposits are also immunohistochemically positive to anti-PRL serum, not to anti-GH serum. Finally, by considering the information present in literature, we have discussed the possible pathogenic mechanisms leading to amyloid deposits in pituitary adenomas.


Quinolinate in brain and cerebrospinal fluid in rat models of congenital hyperammonemia. Children with inborn errors of urea synthesis who survive neonatal hyperammonemic coma commonly exhibit cognitive deficits and neurologic abnormalities. Yet, there is evidence that ammonia is not the only neurotoxin. Hyperammonemia appears to induce a number of neurochemical alterations. In rodent models of hyperammonemia, uptake of L-tryptophan into brain is increased. It has been reported that in an experimental rat model of hepatic encephalopathy, in the ammonium acetate-injected rat, and in patients with hepatic failure and inborn errors of ammonia metabolism, quinolinate, a tryptophan metabolite, is increased. Elevations in quinolinate are of particular concern, as quinolinate could excessively activate the N-methyl-D-aspartate subclass of excitatory amino acid receptors, thereby causing selective neuronal necrosis. We sought to identify an animal model that would replicate the increases in quinolinate that have been associated with hyperammonemia in humans. Levels of quinolinate were measured in hyperammonemic urease-infused rats and ammonium acetate-injected rats. In the urease-infused rat, brain tryptophan was doubled, and serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly increased. Yet, despite the increase in tryptophan and evidence for increased metabolism of tryptophan to serotonin, there were no observed increases of quinolinate in brain, cerebrospinal fluid, or plasma. In the ammonium acetate-injected rat, significant increases of 5-hydroxyindoleacetic acid in cerebral cortex were also observed, but quinolinate did not change in cerebrospinal fluid or cerebral cortex. In summary, we were unable to demonstrate an increase of quinolinate in brain or cerebrospinal fluid in these rat models of hyperammonemia.


[Laboratory diagnosis of Pneumocystis carinii: comparison of cytological, immunofluorescent and immunocytochemical staining]. Authors review several methods for diagnosis of Pneumocystis carinii on BAL fluid in AIDS patients aiming to identify ideal routine technic. Giemsa, Gomori and Toluidine Blue staining. Direct and Indirect Immunofluorescence. Immunocytochemical methods were tested and advantages/disadvantages compared on BAL fluid from AIDS patients. Pneumocystis carinii was detected in 7 out 21 cases (33%). Gomori staining and Toluidine Blue staining were chosen for routine Pneumocystis carinii detection while IF technics are deserved as very useful in fields showing high fungal ++ contamination (inducted sputum).


Serum bilirubin levels, intracranial hemorrhage, and the risk of developmental problems in very low birth weight neonates. To study whether elevated levels of bilirubin in the neonatal period increase the risk of developmental problems for very low birth weight neonates, the investigators used data from a geographically based sample of 495 very low birth weight neonates, born January 1, 1985, to December 31, 1989, who survived to 1 year of adjusted age. Maximum neonatal bilirubin levels were found in medical records. A developmental problem was defined as either cerebral palsy or a Bayley Mental Developmental Index of less than 68 at 1 year adjusted age. Potentially confounding factors were controlled using logistic regression. To control for the effects of intracranial abnormalities (eg, intraventricular hemorrhage), separate logistic regression analyses were carried out for three strata, defined according to the results of cranial ultrasonography. In these analyses, the following odds ratios (with 95% confidence limits) were found for the association of maximum neonatal bilirubin concentration and developmental problems: for subjects without intracranial abnormalities, 0.9 (0.7, 1.9); for subjects with uncomplicated intracranial hemorrhage, 1.5 (0.8, 2.5); for subjects with complicated intracranial hemorrhage or intraparenchymal echo-densities, 1.2 (0.4, 3.6). In summary, in analyses controlled for confounding factors, maximum neonatal bilirubin level was not consistently associated with the risk of developmental problems identifiable at 1 year.


Activation of basolateral Cl- channels in the rat colonic epithelium during regulatory volume decrease. Exposure to a hypotonic medium caused an increase in the diameter of isolated crypts from the rat colon. The increase in cell volume was only transient and lasted about 7 min. Despite of the continuous presence of the hypotonic medium, cell volume decreased again. This regulatory volume decrease (RVD) was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel blocker, and by Ba2+, a K+ channel blocker. Cell-attached patch-clamp recordings revealed that the RVD was associated with the activation of previously silent basolateral channels. These channels were identified after excision of the patch as Cl- channels (28 pS) and as K+ channels (45-60 pS). The RVD was dependent on the presence of external Ca2+. The phospholipase A2 inhibitor, quinacrine, and the lipoxygenase blocker, nordihydroguaiaretic acid, inhibited RVD, while indomethacin had no effect. In Ussing chamber experiments an exposure to hypotonic media caused an initial, transient increase in tissue conductance (Gt), followed by a prolonged decrease in short-circuit current (Isc) and the potential difference (V). The height of the electrical response was dependent on the decrease in the osmolarity in a range from 20 mosmol l-1 to 90 mosmol l-1. The increase in Gt was blocked by NPPB and Ba2+, whereas the decrease in Isc or V was inhibited by NPPB but enhanced by Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)


Chloride channels in cultured human skeletal muscle are regulated by G proteins. The regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the "intermediate" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels.


Pressure-clamp: a method for rapid step perturbation of mechanosensitive channels. Here we describe a pressure-clamp method for applying suction or pressure steps to membrane patches in order to study the activation, adaptation and relaxation characteristics of mechanosensitive (MS) channels. A description is given of the mechanical arrangement of the pressure clamp which involves a balance between negative (suction) and positive pressures. The electronic circuitry of the feedback control is described. We also describe the optimal time response (approximately 10 ms) of the pressure-clamp, the amplitude of pressure resolution (0.2-0.5 mmHg; 27-67 Pa) and the factors influencing these parameters. We illustrate the applications of the clamp on the Xenopus oocyte and cultured skeletal myotubes from dystrophic mouse (mdx) muscle, both of which express MS channels. Studies with pressure/suction pulses indicate that in both muscles and oocytes MS channel activity displays adaptation. The ability to study current relaxations following step changes in pressure/suction using the pressure-clamp in combination with patch-clamp techniques provides the opportunity for analysis of the time, voltage and pressure dependence of the opening and closing of MS channels.


Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates? In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of thapsigargin and caffeine on Ca2+ homeostasis in HeLa cells: implications for histamine-induced Ca2+ oscillations. Several studies have already established that the stimulation of H1 receptors by exogenous histamine induces intracellular Ca2+ oscillations in HeLa cells. The molecular mechanism underlying this oscillatory process remains, however, unclear. A series of fura-2 experiments was undertaken in which the nature of the Ca2+ pools involved in the histamine-induced Ca2+ oscillations was investigated using the tumour promoter agent thapsigargin (TG) and the Ca(2+)-induced Ca(2+)-release promoter, caffeine. The results obtained indicate first that TG causes a gradual increase in cytosolic Ca2+ without inducing internal Ca2+ oscillations, and second that TG and histamine share common internal Ca2+ storage sites. The latter conclusion was derived from experiments performed in the absence of external Ca2+, where the addition of TG before histamine resulted in a total inhibition of the Ca2+ response linked to H1 receptor stimulation, whereas the addition of histamine before TG decreased by more than 90% the TG-induced Ca2+ release. Finally; TG was found to inhibit irreversibly histamine-induced Ca2+ oscillations when added to the bathing medium during the oscillatory process. The effect of caffeine at concentrations ranging from 1 mM to 10 mM on intracellular Ca2+ homeostasis was also investigated. The results obtained show that caffeine does not affect systematically the internal Ca2+ concentration in resting and TG-stimulated HeLa cells, but increases the Ca2+ sequestration ability of inositol-trisphosphate (InsP3)-related Ca2+ stores.(ABSTRACT TRUNCATED AT 250 WORDS)


Group I permuted intron-exon (PIE) sequences self-splice to produce circular exons. Circularly permuted group I intron precursor RNAs, containing end-to-end fused exons which interrupt half-intron sequences, were generated and tested for self-splicing activity. An autocatalytic RNA can form when the primary order of essential intron sequence elements, splice sites, and exons are permuted in this manner. Covalent attachment of guanosine to the 5' half-intron product, and accurate exon ligation indicated that the mechanism and specificity of splicing were not altered. However, because the exons were fused and the order of the splice sites reversed, splicing released the fused-exon as a circle. With this arrangement of splice sites, circular exon production was a prediction of the group I splicing mechanism. Circular RNAs have properties that would make them attractive for certain studies of RNA structure and function. Reversal of splice site sequences in a context that allows splicing, such as those generated by circularly permuted group I introns, could be used to generate short defined sequences of circular RNA in vitro and perhaps in vivo.


Elements of an archaeal promoter defined by mutational analysis. The sequence requirements for specific and efficient transcription from the 16S/23S rRNA promoter of Sulfolobus shibatae were analysed by point mutations and by cassette mutations using an in vitro transcription system. The examination of the box A-containing distal promoter element (DPE) showed the great importance of the TA sequence in the center of box A for transcription efficiency and the influence of the sequence upstream of box A on determining the distance between the DPE and the start site. In most positions of box A, replacement of the wild type bases by adenines or thymines are less detrimental than replacements by cytosines or guanines. The effectiveness of the proximal promoter element (PPE) was not merely determined by its high A + T content but appeared to be directly related to its nucleotide sequence. At the start site a pyrimidine/purine (py/pu) sequence was necessary for unambiguous initiation as shown by analysis of mutants where the wild type start base was replaced. The sequence of box A optimal for promoter function in vitro is identical to the consensus of 84 mapped archaeal promoter sequences.


Temperature-dependent template switching during in vitro cDNA synthesis by the AMV-reverse transcriptase. Reverse transcriptase template switching has been invoked to explain several aspects of retroviral replication and recombination, and has been reported in vitro for the Moloney murine leukemia virus (M-MuLV) reverse transcriptase. During in vitro cDNA synthesis, the avian myeloblastosis virus (AMV) reverse transcriptase can switch from one template to another in a homology-dependent and temperature-dependent manner. Chimeric cDNA molecules are generated within 30 min at high incubation temperatures, with an increasing efficiency from 42 degrees C to 50 degrees C. Such products are detectable only after much longer incubation times when primer extension reactions are carried out at lower temperatures (90 min at 37 degrees C).


Subxiphoid approach for implantable cardioverter defibrillator in patients with previous coronary bypass surgery. From February 1988 until August 1991, 28 patients with prior coronary artery bypass grafting (CABG) received implantable cardioverter defibrillator (ICD) therapy via a subxiphoid approach. Only one patient required conversion to a median sternotomy incision. The mean defibrillation threshold was 11.9 +/- 4.4 J. The mean R wave was 8.2 +/- 3.7 mV. One perioperative death occurred due to heart failure (mortality rate 1/28 [3.50%]). No patient required reexploration for bleeding. The subxiphoid method for ICD electrode implantation is safe and reliable in patients with prior CABG surgery.


A Soviet nuclear pacemaker.

A Soviet nuclear pacemaker. A Soviet nuclear pacemaker is described. It is a large VOO bipolar pacemaker, probably nonprogrammable. It has unique electrode connectors. No isotope leak or excessive radiation hazard was detected. Because we had no knowledge of its end-of-life markers and because of the impossibility of assuming long-term safety, the device was removed.


Suppression of incessant ventricular tachycardia in hypertrophic cardiomyopathy associated with improvement of severe left ventricular dysfunction. A 32-year-old black man presented with a history of palpitations since childhood and two syncopal episodes. He was found to have incessant ventricular tachycardia, impaired left ventricular contraction (ejection fraction 9%), and nonobstructive hypertrophic cardiomyopathy. Procainamide abolished the arrhythmia and the ejection fraction rose to 22% in sinus rhythm. Later treatment was switched to amiodarone, which suppressed the ventricular tachycardia but necessitated pacemaker implantation. He has remained well during the subsequent 2 years. Left ventricular ejection fraction has increased to 47% measured in paced rhythm. The improvement in left ventricular function has been attributed to suppression of the incessant ventricular tachycardia.


Modification of late potentials by intracoronary ethanol infusion. Antiarrhythmic drugs have no consistent effects on the signal-averaged electrocardiogram (ECG) while successful surgical ablation of ventricular tachycardia is known to abolish late potentials. Ten patients with prior myocardial infarction had successful ablation of recurrent sustained ventricular tachycardia by selective ethanol infusion into a small coronary vessel supplying the tachycardia origin. Signal-averaged ECGs were performed before and after initially successful ablation in patients without pacemaker dependence or intraventricular conduction delay to assess the effects on late potentials and to determine if the signal-averaged ECG could predict ventricular tachycardia recurrence. Only four of ten patients were eligible for study and all four had late potentials prior to ethanol ablation. Late potentials were abolished in one patient who has not had an arrhythmia recurrence in 25 months. One patient with sudden death and another patient with ventricular tachycardia recurrence had persistent late potentials post procedure that were modified by a reduction in terminal voltage and lengthening of terminal low amplitude signal. The fourth patient who receives chronic amiodarone had no arrhythmia recurrence in spite of persistent but modified late potentials. Thus, the abolition of late potentials after ethanol ablation may predict freedom from arrhythmia recurrence.


Apparent P wave undersensing in a DDD pacemaker post exercise. Wenckebach behavior of DDD pacemakers occurring when the P-P interval varies between the programmed upper rate interval and the total atrial refractory period is symmetrical in a sense that the pacemaker response during atrial rate acceleration is similar to the pacemaker response during atrial rate deceleration. This phenomenon can be observed in all patients with persistent AV block in whom a DDD pacemaker is implanted, during exercise testing when the spontaneous atrial rate exceeds the selected upper rate, i.e., the programmed upper rate interval. However, this phenomenon will not be observed in all patients with intermittent intact AV conduction during exercise. In this case report we describe a patient who showed an asymmetrical response during a bicycle exercise test. There was 1:1 atrial sensing ventricular pacing until the atrial rate exceeded the upper rate of 140 ppm, while atrial sensing was restored during recovery when the conducted sinus rhythm had decreased to 105 beats/min.


Radiofrequency catheter ablation of the AV node to improve the function of an antitachycardia implantable defibrillator. A case of coexisting atrial fibrillation and ventricular tachycardia in a patient with an implantable cardioverter defibrillator is described. Despite careful reprogramming, the device was not always able to distinguish between the two arrhythmias and continued to deliver inappropriate antitachycardia therapy including DC shocks. Attempts to pharmacologically control the atrial fibrillation were unsuccessful so radiofrequency ablation of the atrioventricular node was performed. Following successful ablation, there have been no further false detections no episodes of further ventricular tachycardia.


Differentiation between monomorphic ventricular tachycardia and sinus tachycardia based on the right ventricular evoked potential. The differentiation between ventricular tachycardia (VT) and sinus tachycardia (ST) is problematic in some patients with implantable defibrillators and/or antitachycardia pacemakers. The integral of the ventricular endocardial evoked response, or paced depolarization integral (PDI), has been demonstrated to undergo characteristic changes with a variety of stimuli including catecholamines, pacing rate, and exercise. We hypothesized that the PDI recorded from a unipolar transvenous right ventricular endocardial catheter would differentiate VT from ST. The PDI was calculated from a unipolar pacing stimulus, delivered via a cathode in the right ventricular apex, and the reference electrode, a quadripolar catheter positioned in the superior vena cava. PDIs were measured in 22 patients during VT and sinus rhythm. The PDI measured during sinus rhythm was 579 +/- 240 microV-sec and the PDI during VT was 894 +/- 411 microV-sec (P < 0.001). In a subset of seven patients, PDIs were measured during VT, sinus rhythm, and ST induced by catecholamine infusion or exercise. In this subset, the PDI during sinus rhythm was 645 +/- 295 microV-sec, during ST 588 +/- 308 microV-sec (9% decrease from sinus, P = 0.05), and during VT 863 +/- 342 microV-sec (33.9% increase, P = 0.01). These data indicate that the measurement of the PDI is potentially useful in differentiating VT from ST.


Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable cardioverter defibrillators. The incidence and cause of electrocardiographically documented spontaneous implantable cardioverter defibrillator (ICD) discharges for a rhythm other than ventricular tachycardia (VT) or fibrillation (VF) (unnecessary shocks) were determined in 241 patients who underwent ICD implantation between March 1983 and November 1991. During follow-up of 24 +/- 20 months, 54 of 241 patients (22%) received a total of 132 unnecessary ICD shocks confirmed by Holter or telemetry monitoring or stored electrograms (Egs) from the ICD. The rhythm preceding these unnecessary ICD shocks was atrial fibrillation in 30 patients, sinus or supraventricular tachycardia (SVT) in 11 patients, antitachycardia pacing triggered by atrial fibrillation or SVT resulting in VT in 5 patients, nonsustained VT in 3 patients, and normal sinus or pacemaker rhythm in 10 patients. Unnecessary ICD discharges occurred most frequently during the first week after implantation or generator replacement (18 of 54 patients [33%]). Unnecessary ICD discharges could be documented more often by stored Egs in patients with devices with Eg storage capability (Ventritex Cadence, 19 of 54 patients [35%]) than by Holter or telemetry monitoring in patients with devices without Egs storage capabilities (34 of 193 patients [18%], P < 0.01), despite a shorter mean follow-up duration of 14 +/- 9 months versus 26 +/- 21 months, respectively. Only six of 54 patients (11%) in whom unnecessary ICD discharges occurred had recurrent unnecessary shocks during 22 +/- 20 months of follow-up after treatment directed at the cause of the first episode or device reprogramming to preclude non-VT rhythm detection.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of an acute increase in atrial pressure on atrial refractoriness in humans. Contraction-excitation feedback has been studied extensively in mammalian ventricles. In contrast, little is known about contraction-excitation feedback in mammalian atria. The objective of this study was to investigate the effect of acute alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness. Twenty patients without structural heart disease participated in the study. In each patient the atrial effective (ERP) and absolute refractory periods (ARP) were measured during AV pacing at a cycle length of 500 msec and an AV interval of 120 msec. Acute increases in atrial pressure were induced by pacing the atrium and ventricle simultaneously for the final two beats of the drive train. The ERP was defined as the longest extrastimulus coupling interval that failed to capture with an extrastimulus current strength of twice the stimulation threshold. The ARP was defined in a similar manner with an extrastimulus current strength of 10 mA. The ERP and ARP were determined using the incremental extrastimulus technique. A subset of patients had the pacing protocol performed during autonomic blockade. As the AV interval of the final two beats of the drive train was shortened from 120 msec to 0 msec, the peak right atrial pressure increased from 7 +/- 3 mmHg to 15 +/- 5 mmHg (P < 0.001). The increase in atrial pressure associated with simultaneous pacing of the atrium and ventricle resulted in shortening of the atrial ERP and ARP by 7.3 +/- 5.2 and 6.2 +/- 3.5 msec, respectively (P < 0.001). Similar results were obtained during autonomic blockade. these findings confirm the presence of contraction-excitation feedback in normal human atria.


In anterior myocardial infarction, frequency domain is better than time domain analysis of the signal-averaged ECG for identifying patients at risk for sustained ventricular tachycardia. Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged ECG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40-250 Hz), the duration of the late QRS < 40 microV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location.


Usefulness and adequacy of sensor data storage and retrieval for rate response simulation. The usefulness of sensor data storage for rate response simulation was evaluated using a new dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay 294-03 [Intermedics Inc.]). The pacemaker can store the sensor output during routine exercise and those values can be used to simulate rate profiles for other rate response settings. The predictive value of this feature was evaluated in three studies (mechanical, external pacemaker, and implanted pacemaker). In the first study, the pacemaker was submitted to three runs of eight different mechanical calibrated to-and-fro movements. In the second study, nine external pacemakers were strapped on healthy volunteers who performed three jogging tests. Finally, the predictive value of the simulation was studied in five implanted patients during three successive walking tests. In each study, the pacemaker was submitted three times to the same activity. The responsiveness was successively set to 5, 1, and 10, and the pacemaker outputs were continuously recorded on a Holter monitor. At the end of the first run, rate profile simulations for slopes 1 and 10 were performed; slope 5 rate response was simulated after the second run. A regression analysis was used to establish the correlation between predicted and achieved pacing rates for each study. The coefficients of correlation between predicted and measured pacing rates for the mechanical, external, and clinical studies were 0.999, 0.985, and 0.823, respectively. The corresponding slopes of regression lines were 1.005, 0.971, and 0.935. Calculated rate profile has a high predictive value and could be used to optimize rate responsive settings without serial exercise testings.


A unique preexcitation pattern related to an atypical anteroseptal accessory pathway. Accessory atrioventricular pathways have traditionally been classified by anatomical location to four areas, namely anteroseptal, posteroseptal, and right and left free walls. Each of these have been associated with a relatively distinct preexicitation pattern electrocardiographically. We describe a patient with a unique ECG pattern suggesting preexicitation to the right ventricular outflow region. Preoperative and intraoperative electrophysiological testing confirmed the presence of an accessory pathway with an atrial insertion site near the His bundle, decremental anterograde conduction, and a ventricular insertion site in the upper part of the interventricular septum. Operative ablation near the atrial insertion site eliminated preexicitation.


Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations. The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure.


Effects of defibrillation shocks delivered directly over a major coronary artery. This study investigated the influence of defibrillator shocks delivered directly over a coronary artery, independent of ventricular fibrillation, on cardiac hemodynamics. Thirty-six open chest, halothane anesthetized pigs were randomized to receive six shocks at one of 5.0, 7.5, or 10.0 joules (J). Shocks were delivered between two mesh electrodes (Medtronic TX-7) sutured onto the epicardium, one over the left anterior descending coronary artery and the second directly opposite on the posterobasal ventricular surface. Shock delivery was synchronized to the R wave of the cardiac cycle, to reduce the risk of inducing fibrillation, with a 5-minute stabilization period between successive shocks. Pressure from the left ventricle, the left anterior descending coronary artery, distal to the mesh electrode and the left circumflex (control) artery and contractility in the regions perfused by both arteries were measured. The shocks invariably produced an immediate (2-second postshock), but transient, depression in systolic pressure of the same magnitude for the left anterior descending coronary artery, circumflex artery and the left ventricle that recovered by 5-minute postshock. There was no dose dependent relationship to energy. Also there was no clear difference in myocardial wall motion between the area perfused by the left anterior descending coronary artery and that perfused by the circumflex artery. These results suggest that shocks up to 10 J delivered over an epicardial artery do not cause arterial spasm and do not compromise coronary artery blood flow.


Familial congenital sinus rhythm anomalies: clinical and pathological correlations. We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome.


Correlation of electrophysiological activation patterns to tension generation in stimulated latissimus dorsi muscle. Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode per se that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions.


The hemodynamic importance of atrial systole: a function of the kinetic energy of blood flow? The relative importance of atrial systole on left ventricular filling was investigated at rest and during exercise in 25 patients with dual chamber pacemakers. The mean blood flow velocity over the mitral valve, the velocities of the rapid filling phase (E), the active filling phase (A), and the E/A ratio were determined by pulsed Doppler-echocardiography. The patients were first examined at rest during AV sequential pacing (DVI) at 70 and 104 beats/min. The investigation was subsequently repeated during atrial synchronous pacing (VDD) at rest and during supine submaximal exercise at workloads adjusted to achieve heart rates corresponding to those during DVI pacing. The mean blood flow velocity at rest did not differ between DVI and VDD pacing at 70 beats/min (0.46 vs 0.49 m/sec). When the resting heart rate was increased to 104 beats/min (DVI) the mean blood flow velocity increased to 0.56 msec (P < 0.001). At a corresponding heart rate during exercise (VDD) the velocity increased to 0.70 msec (P < 0.001). At a resting heart rate of 70 beats/min the E/A ratio (n = 14) did not differ significantly between DVI and VDD pacing. With an increased resting heart rate (DVI) the E/A ratio decreased from 0.94 +/- 0.45 to 0.78 +/- 0.18; NS. When the heart rate increased during exercise (VDD) the E/A ratio increased from 0.75 +/- 0.14 to 0.97 +/- 0.16; P < 0.001. There was a positive correlation between the increase of the mean blood flow velocity and the increase of the E/A ratio during exercise (r = 0.69, P < 0.01). No such correlation was found when the heart rate was changed at rest. Thus, the importance of atrial systole on ventricular filling diminishes during exercise in accordance with increasing blood flow velocity, which by physical principles is related to the kinetic energy. The relative importance of atrial systole is hence inversely correlated to the kinetic energy of the blood flow.


Factors predicting success in DC catheter ablation of accessory pathways. In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias.


Late potentials in a porcine model of anterior wall myocardial infarction and their relation to inducible ventricular tachycardia. In this study, normal values for signal averaged electrocardiographic parameters were assessed in healthy pigs (n = 100) and the development of late potentials after myocardial infarction (n = 41) in relation to inducible ventricular tachycardia was investigated. Normal values are: filtered QRS duration (QRS) < or = 78 msec; root mean square voltage of the averaged QRS complex (V(tot)) > or = 51 microV, and duration of terminal activity below 30 microV (D30) < or = 37 msec. The distribution of the root mean square voltage in the last 30 msec (V30) was biphasic. Two weeks after myocardial infarction, QRS was prolonged from 55 +/- 10 to 66 +/- 19 msec (P < 0.002). D30 was prolonged from 19 +/- 6 msec to 28 +/- 13 (P < 0.002). V30 was decreased from 107 +/- 135 microV to 45 +/- 77 (P < 0.02). The total voltage (V(tot)) was decreased from 195 +/- 78 to 123 +/- 61 microV (P < 0.002). In four pigs (19%) late potentials developed. Sustained ventricular tachycardia was inducible in 11 pigs (52%), ventricular fibrillation in two pigs (10%) and eight pigs (38%) were noninducible. Three of 11 inducible pigs and one of the noninducible pigs had a late potential. The incidence of late potentials and their relation to inducible sustained ventricular tachycardia is comparable to the situation in man. Therefore, this pig model is an attractive alternative to the commonly used dog models.


Intracardiac impedance to determine sympathetic activity in rate responsive pacing. Modern pacemaker technology renders possible the adaptation of pacing rate to hemodynamic requirements. The most ambitious approach aims at restoration of the physiological closed-loop system by utilizing the information supplied by the autonomic nervous system (ANS) and extracted from myocardial contractile performance. Measurement is accomplished by the impedance method using the stimulation electrode as the measuring electrode. The ventricular inotropic parameter (VIP) has been identified as an ANS dependent parameter. A special detection algorithm, regional effective slope quantity (RQ), with high ANS sensitivity has been developed. Rate adaptation has been achieved by using an individually adjustable inotropic index (II). The concept has been evaluated in a multicenter study using a standardized exercise protocol. The results in patients with AV block demonstrate excellent agreement between spontaneous sinus rhythm and the ANS-controlled stimulation rate during different forms of exercise. Measurement of mean arterial blood pressure (MABP) supports the physiological approach of adapting the pacing rate to various types of hemodynamic challenges.


Autonomic nervous system controlled closed loop cardiac pacing. A multicenter clinical study is presented, which focuses on the reestablishment of closed loop cardiac control in patients with chronotropic insufficiency. Using the information about sympathetic tone contained in the myocardial contractility, it is possible to reconnect the heart rate to the physiological control mechanisms. Intracardiac impedance is measured with the ventricular electrode and the ventricular inotropic parameter (VIP) is derived from that. The VIP serves directly as input to the control of heart rate by the pacemaker. Over 200 patients have received autonomic nervous system (ANS) controlled pacemakers. The patient-pacemaker system was investigated in different ways. This included standard exercise tests, long-term studies of every day activities over 24 hours, psychological, and pharmacological challenges. To prove the validity of the approach we specifically looked at (1) the appropriateness of changes in paced heart rate with sympathetic tone during exercise, (2) the correlation between heart rate and sinus rate, if detectable, and (3) the correlation between the echocardiographically determined preejection period (PEP) and the VIP controlled heart rate.


Identifying patients for rate responsive atrial pacing: a new method for patient selection and pacemaker programming. In patients with sinus node disease (SND) and chronotropic incompetence, atrial rate adaptive stimulation (AAI,R pacing) is regarded as the most appropriate pacing mode. Since coronary artery disease is the most common etiology in these patients, we evaluated a new technique combining two-dimensional transesophageal echocardiography and atrial transesophageal pacing to detect pacing induced wall motion abnormalities and assess safe upper rate limits. Thirty-five patients were studied: 26 with and 9 without angiographic coronary artery disease. Stable atrial capture was achieved in all patients using 12 +/- 3 msec pulse width and 12 +/- 4 mA current strength. Sensitivity and specificity for the detection of coronary artery disease was highest for transesophageal echocardiography during pacing (sensitivity 81%, specificity 100%). Simultaneous 12-lead ECG during pacing had lower values (sensitivity 57%, specificity 75%). Pacing induced wall motion abnormalities preceded ST segment changes in all patients. Exercise stress testing showed similar values (sensitivity 62%, specificity 89%). It is concluded that simultaneous transesophageal echocardiography and transesophageal pacing is a safe and useful technique in selecting patients for AAI,R pacing and for the detection of safe upper rate limits, particularly when coronary artery disease is suspected.


Multicenter clinical evaluation of a new SSIR pacemaker. A multicenter clinical evaluation of Sorin Swing 100, a new SSIR pacemaker with a gravimetric sensor, was performed by seven different centers enrolling a total of 89 patients, 56 men and 33 women, mean age 73.1 years, for pacemaker implantation (73 patients) or pacemaker replacement (16 patients). Pacing mode was VVIR in 73 patients and AAIR in 16. The behavior of pacing rate was evaluated 3 months after the implant by performing a 24-hour Holter monitor, an exercise stress test, and tests for the assessment of mechanical external interference (MEI). A physiological behavior of the paced rate was always observed during Holter monitoring. In 52 completely paced patients mean diurnal, nocturnal, and maximal heart rate were, respectively, 74.9 +/- 5.7 ppm, 58.1 +/- 5.8 ppm, and 113.4 +/- 12.7 ppm; a paced rate exceeding 100 ppm was reached on the average 5.6 times/Holter monitor. In all but two patients the sleep rate (55 ppm) was reached during the night or long resting time. During exercise stress test a direct correlation between the increase in pacing rate and the increase in workload was observed; the mean maximal heart rate reached in 49 completely paced patients was, respectively, 102.8 +/- 9 ppm in 17 patients who accomplished stage 1, 116.2 +/- 13.6 ppm in 28 patients who accomplished stage 2, and 133 +/- 6.7 ppm in 10 patients who accomplished stage 3 of the Bruce protocol. MEI testing never increased the pacing rate over the noise rate (10 ppm over the basic rate). In only seven patients the results obtained suggested to change the nominal set up of the pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)


A new acceleration driven pacemaker: rate modulation versus normal sinus rhythm--comparison during treadmill exercise. The pacing rate response of a new acceleration driven pulse generator (SWING 100, SORIN BIOMEDICA) was compared with simultaneous normal sinus rhythm (NSR) during two different treadmill exercises. This pacemaker has a gravitational acceleration sensor able to discriminate between physical activities and vibrations. Six healthy volunteers (three male, three female; aged 21.7 +/- 4.3 years), with the pacemaker strapped to their right infraclavicular area, performed each test three times with different rise response curve (RRC) each time: fast, normal, and slow. The fall response curve used was the same as the rising one during each test. Pacing rates were recorded using the VEGA analyzer (SORIN BIOMEDICA) and compared with simultaneous NSR recorded by a 7-channel ECG recorder (MINGOGRAF 7, SIEMENS). During all tests immediate (within seconds) rapid increase in pacemaker rate was seen up to about 60 seconds, then a slower increase followed thereafter. The mean correlation between pacing rates and NSR during the Bruce tests were 0.7941 +/- 0.10, 0.8562 +/- 0.14, and 0.8292 +/- 0.07; during the discontinuous tests 0.7292 +/- 0.16, 0.7233 +/- 0.10, and 0.7480 +/- 0.11 for fast, normal, and slow RRC, respectively. Each 30 seconds, nonsignificant differences were present between pacing rate and NSR during all the discontinuous tests; similar responses were observed only during the first two stages of Bruce tests after which NSR was significantly higher than pacemaker rates. The speed of rise to upper rate was the main difference between the different programs (fast, normal, and slow). The discontinuous tests showed that the pacemaker responds more to speed than to grade.(ABSTRACT TRUNCATED AT 250 WORDS)


A new motion responsive pacemaker: first clinical experience with an acceleration sensor pacemaker. A new accelerometer-based adaptive rate pacemaker (EXCEL VR) was evaluated to investigate its behavior at nominal settings during treadmill exercise testing and postural changes. Eight patients with sinus rhythm were selected to compare intrinsic heart rate to sensor mediated rate. Throughout exercise treadmill testing, changes in the sensor mediated rate closely paralleled actual physiological changes. The Pearson product moment correlation of pacing rate with sinus frequency, calculated for all patients, was r = 0.82 (P = 0.001). Change in the patient's physical position resulted in immediate change in sensor rate, which corresponded appropriately to the type of position change and activity level. Average (+/- SD) pacing rate was 62.4 +/- 2.7 beats/min supine; 67 +/- 3.8 beats/min sitting; 69.8 +/- 6.4 beats/min standing; 81.6 +/- 8.7 beats/min slow walking; and 96.8 +/- 1.3 beats/min fast walking. After 4 minutes of recovery, the average pacing rate dropped to 65 +/- 3 beats/min. The interaction between the accelerometer and the pulse generator at nominal settings was accurate and infrequently required the use of its many programming options. The accelerometer sensor and pulse generator algorithm in this device during postural change and exercise resulted in physiological-like changes in sensor mediated heart rate.


Clinical results of automatic slope adaptation in a dual sensor VVIR pacemaker. Manual slope programming in rate adaptive pacemakers can be time consuming. This may become worse with dual sensor devices. The remedy is to let the pacemaker automatically learn the slopes. Fast learning replaces initial manual slope programming. Daily learning is a continuous process to determine and optimize slopes during daily life. Both methods are known for a QT sensing pacemaker. Fast learning is known for other single sensor devices. The aim of this study was to follow daily learning in a QT and activity dual sensor pacemaker, starting with factory slope settings. Six patients were studied for about 8 weeks. The daily learning algorithm appeared to be effective, showing the desired regulation processes. It took 2-5 weeks to reach full rate response.


Clinical observations with a dual sensor rate adaptive single chamber pacemaker. The Topaz model 515 (Vitatron B.V.) is a dual sensor rate responsive pacemaker for single chamber stimulation. It can be driven by activity counts (ACT) and QT interval measurements. Inappropriate rate modulation due to one sensor can be corrected by "sensor cross-checking." It was implanted in ten patients (20-86 years) of whom seven had complete heart block and atrial arrhythmias. After implantation T-wave amplitude ranged from 0.9 mV-3.5 mV. T-wave sensing ranged from 88%-99% in 9/10 patients at the follow-up of 3 weeks. Eight patients remained in default setting of the activity threshold, after evaluation with a short walking test. An exercise test was performed on all patients. In one test, QT sensing was marginal because of lead implantation in the right ventricular outflow tract. Therefore, this pacing rate was only modulated by ACT sensing. All others were tested with equal contribution of information from both sensors (ACT = QT). In 7/9, rate response was satisfactory. When the treadmill was repeated with ACT in five of these seven patients, rate generally accelerated too fast. In one patient the setting was adjusted to "QT > ACT," because of inappropriate acceleration due to activity sensing, in another it was adjusted to "QT < ACT" because of delayed response to activity. The pacing rate and the ACT during treadmill tests in "QT = ACT" mode were more closely correlated in the first 3 minutes, compared with the last 3 minutes. We feel that rate modulation with this new pacemaker is adequate. Sensor blending and sensor cross-checking are of clinical importance.


Follow-up of a minute ventilation rate adaptive pacemaker. Although rate adaptive pacemakers are now frequently prescribed, there is limited information regarding long-term follow-up of patients with a pacemaker capable of rate adaptation. We have examined our patients in whom a pacemaker capable of rate adaptation via a sensor that determines minute ventilation has been implanted. After following a group of 42 patients for a mean of 13.2 months we have found this to be a reliable rate adaptive pacing system. The sensor was reliable long term, the system is easy to program, and sensor settings were changed infrequently.


Clinical experience with a new multiprogrammable dual chamber pacemaker. We evaluated the clinical performance of a new dual chamber pacemaker, ELA Chorus, in 35 patients. This device incorporates linear rate adaptive AV delay (AVDR), rate smoothing, fallback, impedance telemetry, pacemaker mediated tachycardia (PMT) recognition and reprogramming software, intracardiac electrogram displays, autothreshold testing, diagnostic data, battery depletion curves, and laptop computer programming. Mean patient age was 68 years; 18 patients had AV block, six had sinus node dysfunction (one with AV block), nine had carotid sinus hypersensitivity (three with AV block), and two had vagally mediated syncope. At hospital discharge, programming was DDD with a mean low rate of 60 (50-70) beats/min, mean high rate of 126 (120-154) beats/min; AVDR was ON in 21 patients, rate smoothing ON in six patients, fallback ON in six patients, and PMT reprogramming algorithm ON in 27 patients. Pacemaker follow-up involved 500 clinic visits over 14.3 months (1-36). Three patients developed atrial fibrillation, reprogrammed to DDI mode (two patients) or fallback (one patient). Fallback was used 617 times. PMT occurred 427 times in six patients; the PMT algorithm reprogrammed AV delay and postventricular atrial refractory period (PVARP) automatically, a function unique to the Chorus. Intracardiac electrograms and autothreshold testing improved follow-up efficiency. This new dual chamber pacemaker enhances programming flexibility and improves diagnostic accuracy at follow-up.


Facilitation of DDD follow-up using the DDT mode. To facilitate follow-up, modern dual chamber pacemakers provide a variety of diagnostic features like ECG interpretation channels and intracardiac electrograms. For evaluation of the sensing performance at rest and during exercise, for assessment of the presence of crosstalk, and for measurement of the retrograde conduction time, dual chamber triggered pacing, particularly the DDT mode, can be used alternatively or additionally in pacemakers equipped with this option. In contrast to ECG interpretation channels, ECG documentation is not required for evaluation of the sensing performance, because the triggered pulses serving as markers for sense events can also be seen on the monitor. Selection of the DDT mode not only as temporary but also as permanent program serves to facilitate pacemaker ECG interpretation for exercise tests and Holter recordings as well.


External vibration interference of activity based rate responsive pacemakers. The change of the pacing rate in response to external vibration interference was assessed in four rate responsive pacemakers with a piezoelectric crystal (Medtronic Activitrax 8403, Siemens Sensolog 3, Biotronik Ergos 01, and Medtronic Legend 8417) and one with an accelerometer (CPI Excel VR 1119). They were tested in the laboratory. External vibration was simulated in vitro by exposing the different pacemakers to a controlled sinusoidal vibration force generated by a Millar pressure vibration amplifier type MGM-30 (Millar Instruments, Inc., Houston, TX, USA). All pacemakers were programmed at standard settings. Two types of vibration forces were applied: (1) one with varying amplitude but with constant vibration frequency; and (2) one with varying frequency but with constant vibration amplitude. In this manner curves of pacing rate versus vibration forces versus vibration frequency were obtained. High vibration forces and low vibration frequencies were associated with the highest pacing rate response. In this experimental setting, the pacemaker based on the accelerometer principle apparently was the least sensitive to high frequency vibrations, which are known to be related to environmental interference. It also seemed more appropriately responsive in the lower frequency range, which is more appropriate for the detection of true physiological activity.


Atrial arrhythmias in dual chamber pacing and their influence on long-term mortality. A retrospective study of 252 patients who received a DDD pacemaker between October 1982 and December 1990 was performed. During a mean follow-up of 30 months, reprogramming to the VVI mode was necessary in 39 patients (15.5%). Technical problems causing downgrading occurred 15 times, of which 13 problems became permanent. A total number of 24 patients had sustained atrial arrhythmias, including 14 with atrial fibrillation and 10 with atrial flutter. In this group, conversion to sinus rhythm could be obtained in 38%. After 2 years, reliable DDD pacing was maintained in 86% of the surviving patients. The survival after 1 and 2 years was 94% and 89%, respectively, and was not influenced by arrhythmias or technical problems. We conclude that atrial arrhythmias including flutter are the most important reasons for reprogramming to the VVI mode, although in an important number of patients, predominantly those with flutter, restoration of AV synchrony can be obtained. The high number of patients with atrial flutter could imply some role for DDD devices offering the option of antitachycardia pacing. Reprogramming of the pacing mode did not influence mortality.


Mixed microprocessor-random logic approach for innovative pacing systems. Modern pacing systems are becoming more and more sophisticated. Conversion of the information supplied by a sensor into suitable parameters for a rate controlling algorithm and the management of complex timing are common tasks for an integrated circuit (IC) in cardiac pacing. An effective solution consists of using a microprocessor to implement algorithms and pacing modes in a flexible way. The key point of using the same hardware resources for different tasks on a time sharing basis allows the design of a less complex IC when compared to a random logic structure with the same performances. The major design problems in a full microprocessor solution are its relatively low operating speed due to the low frequency clock necessary for low current drain, and the sequential structure of the machine itself. This can lead to unacceptable timing inaccuracy in all situations requiring the management of complex decision trees. In order to take full benefit from the advantages of a microprocessor structure without these drawbacks, a mixed microprocessor-random logic approach has been investigated. This architecture uses a microprocessor core to perform all high level nonreal-time operations (setup of the pacing cycle, data reduction and processing, data integrity checks) while a set of random logic peripherals is used for all critical timing aspects.


Clinical interest of a sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia in dual chamber pacing. A sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia (SVT) is included in a dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay, 294-03, Intermedics Inc.). According to the intensity of concomitant exercise, the ventricular pacing rate is limited either to the programmed maximum pacing rate (MPR) or to an interim lower limit, called "conditional ventricular tracking limit" (CVTL). The MPR prevails over the CVTL when the sensor calculated pacing rate exceeds the minimal rate by more than 20 beats/min. The purpose of the study is to determine the clinical safety and efficacy of this algorithm in patients with intermittent SVT. A Relay was implanted in four patients with a bradycardia/tachycardia syndrome and in four patients with complete atrioventricular block (CAVB). All had episodes of paroxysmal atrial tachycardia. The units were programmed in DDDR: rate responsive parameters were adjusted by simulating the rate response during three levels of exercise to let the MPR override the CVTL only during strenuous exercise. Holter monitors and exercise testings were performed at 3-month follow-up. In seven patients, Holter recordings showed supraventricular arrhythmias at rest with a ventricular pacing rate limited to the CVTL. Appropriate rate increases during exercise testings were also demonstrated. Three devices had to be reprogrammed in DDIR (one patient suffering from nearly permanent atrial flutter and two patients not tolerating the CVTL pacing rate at rest). The CVTL algorithm is effective in protecting against high ventricular pacing rates during supraventricular arrhythmias. It allows the selection of the DDDR mode even with a high MPR in patients with intermittent SVT.


In vitro evaluation of a sensor sensitive to acceleration forces included in a new rate modulated pacemaker. The characteristics of the sensor and rate adaptive algorithm included in a new dual chamber rate responsive pacemaker (Relay 294-03, Intermedics, Inc.) were studied by submitting the device to calibrated to-and-fro movements of specific frequencies and peak accelerations by means of a mechanical arm connected to a speed adapter. Atrial pacing rate was continuously recorded on a Holter monitor. The influences of the frequency, the magnitude, and the axis of the acceleration forces as well as the reproducibility of the rate response were evaluated. (1) The sensor was sensitive to frequencies ranging from 0.5 to 7 Hz with a peak sensitivity at 3 Hz; (2) the pacing rate was not affected during movements at frequencies > 6 Hz, commonly presented as nonactivity related signals (car, bus transportation, drilling....); (3) the pacing rate increased as a function of the acceleration magnitude up to 0.5 G (0.3 G for 3 Hz), then remained constant. This level of acceleration usually corresponds to high degrees of activity; (4) rate response was maximum when acceleration was directed in the anteroposterior direction; (5) reproducibility of the rate response was excellent (R2: 0.999; slope of the regression line: 0.999). Relay 294-03 is a low frequency signal sensing rate modulated pacemaker using an accelerometer sensitive to motion, mainly in the anteroposterior direction.


Feasibility of using intracardiac impedance measurements for capture detection. Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.


Reliability of an automatic sensing algorithm. Automatic adaptation of the atrial sensitivity was evaluated in 18 patients with dual chamber pacemakers (Intermedics, Inc., Relay) in the unipolar mode. After atrial sensitivity was stabilized in the upright position, patients underwent a 1.0 W/kg body weight exercise for 5 minutes. A 24-hour Holter ECG was recorded, and the maximum and minimum atrial sensitivity values reached were stored in the memory of the pulse generator. In a second series of 12 patients, Holter ECGs were recorded twice, starting with the same sensitivity but with automatic adaptation alternately switched "on" or "off." Results of the exercise test: mean atrial sensitivity declined from 2.30 +/- 0.77 mV to 2.03 +/- 0.68 mV. There was no change in five patients, a slight increase in two patients, and lowering of the atrial sensitivity was observed in 11 patients, the difference ranging from 0.2 to 1.0 mV. A total of two P waves in two patients were missed by the atrial amplifier. The minimum and maximum sensitivity reached during Holter monitoring averaged 2.31 +/- 0.67 mV versus 1.72 +/- 0.71 mV (difference 0-1.7 mV). Normal pacemaker function was found in six patients, including one patient without any intrinsic atrial activity. Malsensing of less than five P waves occurred in four patients. More than 50 sensing defects resulted from ectopic atrial beats (four patients). We observed atrial oversensing in three cases; one patient showed atrial over- and undersensing. The comparison between fixed and variable sensitivity did not reveal any superiority of automatic adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison of external rate responsive pacemakers with identical implanted units. Seven patients with previously implanted accelerometer-based DDDR pacemakers had an identically programmed external pacemaker taped onto their chest. Both units underwent a simultaneous test to set the sensitivity of the accelerometer. The units were then programmed to record the pacing rates for a 15-minute period. The patients underwent an exercise course that included walking and stairs. After the exercise, the patients sat for 3 minutes and the pacing rates from the test were telemetered. The pacing rate was compared at 2 minutes, 4 minutes, peak, and 3 minutes postexercise. The mean standard deviation (SED) for the external pacemaker was 97.9 at 3.53 ppm, 102 at 10.6 ppm, 106 at 8.94 ppm, and 71.3 at 2.29 ppm at 2, 4, peak, and decay, respectively. The mean SED for the implanted pacemaker was 98.1 at 5.76 ppm, 100 at 10.2 ppm, 104 8.24 ppm, 72.4 at 2.88 ppm at 2, 4, peak, and decay, respectively. Difference between pacemakers in ppm was 0.286, 2.0, 2.71, and 1.14 at 2, 4, peak, and decay, respectively. A 95% confidence interval in ppm was -5.28 to 5.85, -10.1 to 14.1, -7.30 to 12.7, and -1.89 to 4.17 at 2, 4, peak, and decay, respectively. In all patients there was a high confidence correlation between the implanted and external unit. An external unit can be used to predict the rate response of an accelerometer-based pacemaker without any adjustments to the pacing parameters.


Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing. Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period.


Initial clinical experience with a single pass VDDR pacing system. Although ventricular rate adaptive pacing (VVIR) improves exercise capacity and cardiac output compared to constant rate ventricular pacing (VVI), this pacing mode does not provide benefit of atrioventricular (AV) synchrony. We evaluated the use of a custom-built VDDR pacing system using a single pass, ventricular lead, which detects endocavity P wave using a pair of diagonally arranged atrial bipolar (DAB) electrodes. In the VDDR mode, AV synchrony is enabled and the P wave rate is used in conjunction with an accelerometer based activity sensor for rate adaptive pacing. A VDDR pacemaker was implanted in three patients with complete AV block (mean age 63 +/- 1 year) and the mean implantation time was 29 minutes. Mean P wave amplitude was 2.4 mV (1.2-4.2 mV) at implantation and telemetered P wave amplitude was stable over a follow-up of 6 months. At a sensitivity of 0.2 mV, stable P wave sensing was observed during breathing maneuvers, arm swinging, myopotential induction, and Holter recording. Paired exercise tests performed in the VDDR and VVIR modes showed higher cardiac output at rest, during exercise, and in the recovery period in the VDDR pacing mode. Thus VDDR pacing using a single pass lead is superior to VVIR pacing by enabling P synchronous ventricular pacing without adding to the complexity of implantation.


Complications of single lead VDD pacing in 35 patients with AV block. The implantation of a VDD system is comparable to that of a VVI system, but its management is associated with typical complications of dual chamber pacing. In 35 patients with symptomatic AV block and normal sinus node function, two different VDD pacing systems were implanted. Most of the complications described and their mode of resolution were common to VDD and DDD pacing; however, the VDD system eliminated the need for two separate leads. We, therefore, favor single lead VDD pacing in the treatment of complete AV block with normal sinus node function.


VDD single pass lead pacing: sustained pacemaker mediated tachycardias unrelated to retrograde atrial activation. Pacemaker mediated tachycardias (PMTs) are a well known complication of P synchronous pacing. Although the initiating mechanisms are several, all of them are associated with retrograde atrial activation, which is sensed by the atrial sensing channel, resulting in ventricular pacing. In 19 patients suffering from symptomatic AV conduction disturbances and normal sinus node function, a VDD pacing system connected to a single pass ventricular lead with dual chamber electrodes was implanted. The bipolar atrial electrode, floating in the right atrium, was used to detect endocardial atrial electrograms that were differentially processed within the pacemaker for optimal discrimination and filtering of undesirable signals. The widely programmable atrial sensitivity (amplitude and filtering) allowed stable P synchronized ventricular pacing in all patients, but in five of them, sustained PMTs not related to retrograde atrial activation was documented during the follow-up. The common mechanism for the onset and maintenance of these PMTs was traced to the abnormal sensing of the terminal forces of ventricular activation and/or of the T wave. The possibility of interferences between ventricular and atrial electrodes (crosstalk) was also considered. The reduction of atrial channel sensitivity represented in all cases the only effective procedure to prevent this type of PMT. In conclusion, the bet signal to noise ratio is an important endpoint to assure the proper function of a single lead VDD pacing system. Furthermore, using the differential amplifier built within the pacemaker, consideration should be given to the optimal mode of rejection of the terminal forces of the QRS and T wave.


Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing. In eight patients (age 62 +/- 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 +/- 20 vs 110 +/- 27 beats/min, P < 0.02), higher [VO2 max (25.4 +/- 6.1 vs 21.5 +/- 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 +/- 5.0 vs 15.8 +/- 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 +/- 193 vs 472 +/- 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Aerobic capacity in rate modulated pacing. Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and implanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (AT) with the following heart rates: DDD 84 +/- 3, VVIR 110 +/- 5, and DDDR 116 +/- 6 beats/min. Mean oxygen uptake (VO2, mL/kg per min) at AT was 7.4 +/- 0.3 in DDD and VVIR modes. A 12% increase was measured in DDDR mode (8.3 +/- 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO2 and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise.


Comparison of intrinsic versus paced ventricular function. There is increasing evidence supporting the benefits of providing optimum AV delay in cardiac pacing, though controversy exists regarding its value and the benefits of intrinsic versus paced ventricular activation. This study compared various AV delays at rest in patients whose native AV delays were > or = 200 msec. Only patients with DDD pacemakers who had intact AV conduction and normal ventricular activation were included in the study. Nine patients were studied. Ten studies were performed. Evaluation was done in AAI and DDD modes at paced heart rates of 60/min or as close as possible to the intrinsic heart rate if this was > 60/min. Stroke volume (SV) and cardiac output (CO) were measured. When AV sequential pacing in the DDD mode with an optimum AV delay was compared to AAI pacing with a prolonged AV interval, the average optimum AV delay in the DDD mode was 157 msec and ranged from 125 to 175 msec. The average AV interval in the AAI mode was 245 msec and ranged from 212 to 300 msec. In the DDD mode, there was an overall significant improvement in CO of 11% and SV of 9%. Patients with intrinsic AV conduction times of > 220 msec showed an overall significant improvement in CO of 13% and SV of 11%. In patients with intrinsic AV conduction times of < 220 msec, an improvement in CO of 6% and SV of 4% was seen. (1) An optimum AV delay is an important component of hemodynamic performance; and (2) AV sequential pacing at rest with an optimum AV delay may provide better hemodynamic performance than atrial pacing with intrinsic ventricular conduction when native AV conduction is prolonged > 220 msec.


Precision of impedance cardiography measurements of cardiac output in pacemaker patients. Objective hemodynamic assessment of pacemaker patients is necessary for gauging responses to changes in programming or other conditions that affect the circulation. Impedance cardiography permits noninvasive, repetitive determinations of cardiac output at short intervals, but data regarding variability of this method in patients with pacemakers is unavailable. Thirty-eight patients with implanted pacemakers (24 DDD, 14 VVI) and six normal subjects were studied. A computerized impedance cardiograph was used to calculate cardiac output from the product of the first derivative of the thoracic impedance signal (dZ/dt), the ventricular ejection time, and heart rate. Each patient was studied while supine after a period of at least 15 minutes of rest and repeated impedance measurements (about ten) were performed. Fourteen patients were studied in sinus rhythm, 24 were studied during DDD pacing, and 32 patients were studied during VVI pacing. Cardiac and stroke indices were calculated 706 times on the basis of 11,296 accepted beats. Variability was assessed by methods that analyzed serial measurements and variability between two consecutive and nonconsecutive measurements. The mean indices and coefficients of variation of two measurements and of serial measurements in sinus rhythm and during DDD pacing were 4%; in VVI it was 6%. The precision of impedance cardiography in all pacing modes, as demonstrated by analysis of variability, indicates that detected changes of stroke volume and cardiac output > 7% on serial (two and more) measurements, performed by the same operator and during the same session, represent true hemodynamic alterations with 95% confidence.(ABSTRACT TRUNCATED AT 250 WORDS)


Diastolic mitral regurgitation in patients with first-degree atrioventricular block. Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 +/- 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 +/- 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 +/- 0.06 to 0.20 +/- 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 +/- 0.03 to 0.05 +/- 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgitation (r = 0.92, P < 0.001). Although cardiac output (3.9 +/- 0.05 L/min) and pulmonary capillary wedge pressure (5.1 +/- 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 +/- 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)


Orthostatic responses in patients with DDD pacemakers: signs of autonomic dysfunction. Responses to orthostasis may be altered in states associated with autonomic dysfunction. Computerized impedance cardiography, a noninvasive method for continuous assessment of stroke volume and mean blood pressure, was utilized to study the postural hemodynamic changes in eight normal and 27 patients with DDD pacemakers. Twenty patients with complete heart block (five with heart failure) were studied in the VDD mode and seven patients with sick sinus syndrome were assessed in DVI (four) or VDD (three). The results with pacemaker patients are significantly different from those observed in normal. Pacemaker patient responses to standing included: (1) a reduction in systolic, diastolic, and mean blood pressure; (2) an increase in heart rate in patients with intact sinus node function and no change in patients with sick sinus syndrome; and (3) stroke volume was unchanged in patients with sick sinus syndrome or heart failure and only modest reduction occurred in the remaining patients. (1) No reduction in stroke volume during upright posture occurs in DDD patients with sick sinus syndrome and this appears to be a compensatory reaction to an inadequate heart rate response to standing; (2) The hemodynamic response of DDD patients to the assumption of an upright posture is consistent with autonomic dysfunction; and (3) The primary cause for autonomic dysfunction in DDD patients may be the asynchronous ventricular depolarization caused by right ventricular pacing.


Noninvasive transcutaneous cardiac pacing: modern instrumentation and new perspectives. Noninvasive transcutaneous cardiac pacing has evolved from a simple stand alone unit with no ventricular sensing to a complete cardiac arrest resuscitation system combining synchronous pacing and defibrillation capabilities and using a single set of multifunction electrodes. In current instrumentation, four configurations exist including stand alone unit, modular configuration, built-in monitor and recorder, and built-in monitor, recorder and defibrillator. In present day devices, ventricular sensing, extensive programmability, and large surface electrodes are general features. Capture monitoring requires specific integrated electrocardiographic capability. Future developments are expected to involve low threshold electrode technology, integrated mechanical monitoring, and interdevice electrode compatibility.


Observations on induction and termination of paroxysmal supraventricular tachycardia by external pacing. Paroxysmal supraventricular tachycardia (PSVT) can be reproducibly induced and terminated by critically timed atrial or ventricular depolarizations. In this study, noninvasive transcutaneous (external) cardiac pacing (NTCP) was compared to endocardial ventricular pacing for the termination and induction of PSVT. In 24 patients, either atrioventricular (AV) nodal reentrant tachycardia or AV reciprocating tachycardia was reproducibly terminated with either critically timed ventricular depolarizations or overdrive ventricular pacing from an endocardial right ventricular site. There were 32 trials of NTCP attempts to interrupt PSVT in the 24 patients. External pacing was successful at terminating PSVT in 23 patients and in 30 of 32 (94%) trials. In 20 patients, there were 26 trials of external pacing attempts to induce PSVT. External pacing initiated PSVT in 21 of 26 trials (81%). The pacing sequences used to induce and terminate PSVT with external pacing were copied from the endocardial sequences. The external pacing threshold averaged 77 +/- 22 mA but the current needed to terminate PSVT was about 1.5 greater than threshold at 117 +/- 27 mA. Serial external pacing studies were performed in seven patients. The thresholds for external pacing were similar from trial to trial as were the mode of termination and induction between the endocardial and external methods. External pacing can terminate most AV reciprocating tachycardias and many AV nodal reentrant tachycardias. It appears promising as a means of inducing PSVT. However, the high stimulation amplitudes needed will prohibit wide acceptance of external pacing for induction and termination of PSVT.