Surface tension of amniotic fluid lipid extracts: prediction of pulmonary maturity. The surface tension (ST)-lowering properties of an amniotic fluid lipid extract can provide a rapid and reliable means of predicting pulmonary maturity. One hundred and eleven samples from 91 patients were analyzed. A surface tension of less than 56 dynes per centimeter at 120 microliter of extract and less than 46 dynes per centimeter at 220 microliter of extract denoted pulmonary maturity. Values greater than these indicated immaturity. Among fluid samples studied within 48 hours of delivery for the presence or absence of respiratory distress syndrome (RDS) in 71 patients, there were no false positive ST values, while 7 of 22 patients with immature values developed RDS. Surface tension correlates well with the lecithin/sphingomyelin (L/S) ratio but provides clearer definition than the L/S ratio when compared to outcome. Blood and meconium contamination make the surface tension of fluid from babies with pulmonary immaturity appear mature. Identical twins with dissimilar ST values and outcome, as well as serial samples from individual patients, are analyzed and discussed.


The prediction of fetal oxygenation by an on-line computer analysis of fetal monitor output. The deceleration delay index (DDI) is a statistical parameter computed by an on-line system which analyzes fetal monitor output for the temporal relationship between each uterine contraction and any associated deceleration of the fetal heart rate. A similar parameter describing this relationship is known to be quantitatively predictive of fetal oxygenation in the rhesus monkey, a species for which the level of fetal oxygenation is also known to be directly and progressively related to aberrations in the vital signs, to brain damage, and to fetal death. Thus, the DDI should be of significant, practical value in predicting fetal hypoxia at a time early enough to avert severe neonatal depression and/or hypoxic brain damage. A blind clinical trial of 106 parturients is presented which supports this concept by showing the DDI to be highly correlated with another oxygenation-associated parameter, the one-minute Apgar score.


A modern approach to management of pregnant diabetics: a two-year analysis of perinatal outcomes. Increased understanding of maternal-fetal carbohydrate homeostasis together with modern perinatal technology now provides a more rational basis for obstetric management of the pregnant diabetic patient. These concepts were applied at MacDonald House in the care of 96 diabetic pregnant women over a two-year period. Pregnancy outcomes were compared with prior experiences with the same group of women. The perinatal mortality rate was reduced from 13.5 to 4.2%, and the rate of macrosomia (infants large for gestational age) was reduced from 30.9 to 17.7%. Patients with gestational diabetes, with a prior loss rate of 8.3%, suffered no losses in the current series. Maternal age was not found to correlate with an untoward outcome in this subgroup.


The future function and fortune of ovarian tissue which is retained in vivo during hysterectomy. Hysterectomy was performed for 2,132 private patients; one third were done vaginally and two thirds, abdominally. Ages ranged from the 20's through the 80's, but 55% were between 40 and 55 years of age. Ovarian function was retained at the time of hysterectomy in 1,263 patients; ovarian tissue was retained in 1,557. Based on clinical criteria, 525 patients had continued ovarian function until last examined (one to 23 years); 328 had continued ovarian function until the end of the study (one to 25 years); 410 patients had cessation of ovarian function during the study at ages ranging from 41 to 64 years. Fourteen patients required second operations: three for hemorrhagic physiologic cysts, two for adhesions, one for ovarian endometriosis, four for cystadenomas, and four for ovarian cancer. Two cancer patients died; two are alive and well, five and 15 years after the second operations.


Clinical application of high-risk scoring on an obstetric service. Obstetric risk scoring is a formalized way of recognizing, documenting, and cumulating antepartum and intrapartum factors to predict later complications for mother, fetus, and infant. If simple, practical, and reliable, risk scoring can be clinically useful in determining appropriate levels of care. In this prospective study, antepartum and intrapartum risk scales were integrated into the clinical record, and the relationship of risk scores to outcome was evaluated for 1,275 consecutively delivered gravid women. The forms could be simply and quickly filled out by the staff. Increased risk on both scales was significantly related to lowered one- and five-minute Apgar scores. The perinatal mortality rate increased from 0 to 93.4 per thousand from the lowest to the highest risk group. More than 80% of all perinatal deaths occurred in the one quarter of patients in the highest risk group. These results suggest that this risk scoring system can be used effectively in a clinical setting to identify patients at increased risk for neonatal depression and perinatal death.


Uterotubal implantation and obstetric outcome after previous sterilization. The liberalization of sterilization policies has resulted in an increased number of patients requesting tubal reconstructive surgery. From 1973 through 1975, a total of 18 patients were operated upon by the authors for tubal reconstructive surgery following sterilization. These patients had had either postpartum sterilization of the Pomeroy technique or interval laparoscopic cauterization and cutting. The operative technique with an open uterine approach is described in detail. This technique warrants further evaluation, particularly following laparoscopic sterilization when end-to-end anastomosis is precluded.


Fetal growth retardation associated with maternal administration of immunosuppressive drugs. Since maternal-fetal immunogenetic disparity facilitates growth of the fetoplacental unit, nonspecific depression of the maternal immune system by immunosuppressive drugs could result in previously unrecognized adverse effects such as fetal growth retardation. To test this hypothesis, groups of 6 to 8 primigravid Fischer female rats mated with DA or Fischer male rats were treated with saline (controls) or either cyclophosphamide (Cytoxan) or azathioprine (Imuran) in doses similar to those used therapeutically in human subjects. It was found that these drugs caused an increased incidence of fetal death and produced fetal and neonatal growth retardation. Smaller placentas and fetuses reflected a decrease in cell number rather than cell size whereas water, fat, and protein content were only minimally affected. Analyses of mean maternal weight gain, spleen weight assays, and changes in the lymph nodes draining the uterus indicate that effects detrimental to the offspring are primarily the result of immunologic and cytotoxic mechanisms. Moreover, a review of the literature suggests that these immunosuppressive agents are also associated with small-for-gestational age infants in human pregnancies.


Perinatal mortality rate at a community hospital, 1956 to 1975. This paper is a review of the perinatal mortality rate and its components stillbirths and neonatal deaths, for the years 1956 through 1975 at Memorial General Hospital, Las Cruces, New Mexico. It is an attempt to assess major medical factors, such as specialization and cesarean section, and weigh their effect on these indices of the quality of perinatal medical care. Other factors considered in the analysis were: ages of mothers, parity, birth weights, and socioeconomic, educational, and motivational factors. The apparent impact of direct medical care factors is considerably less than would be expected.


Incidence and spontaneous resolution of postpartum bacteriuria. On the first postpartum day, 53 patients (17.2 per cent) had asymptomatic bacteriuria. Spontaneous resolution of bacteriuria occurred in 40 (75.5 per cent) of the 53 patients by the third postpartum day--the most appropriate time to identify patients with true asymptomatic bacteriuria.


Comparative study of amniotic fluid and maternal blood serum human placental lactogen in normal and prolonged pregnancies. The levels of human placental lactogen (hPL) were measured in maternal blood and amniotic fluid in normal and prolonged pregnancies. Statistical analysis of the hPL levels showed that values rose in both blood and amniotic fluid, reaching maximum levels between Weeks 34 and 36 (6.70 microgram per milliliter in blood serum, 0.85 microgram per milliliter in amniotic fluid). Thereafter, there was a decline, a significant fall occuring between Weeks 40 and 42 and in the prolonged pregnancy group (43 weeks and more) (t = 6.9 and p less than 0.001 in serum levels; t = 3.9 and p less than 0.001 in amniotic fluid levels). There was also a very close correlation (r = 021; p less than 0.005) between maternal blood and amniotic fluid hPL levels in normal pregnancies before labor.


Interrelationship between glomerular filtration rate and renal transport of sodium and chloride during fetal life. The maturation of the glomerular filtration rate (GFR) and the interrelationship between the GFR and the renal transport of sodium and chloride have been evaluated during the last trimester of gestation with the use of long-term experiments in fetal lambs. An increase in GFR (milliliters per minute) parallel to the increase in fetal body weight was demonstrated; however, no significant change was shown when the GFR (milliliters per minute per kilogram of fetal body weight) (1.141 +/- 0.079) was related to fetal body weight or gestational age. There was a constant increase in sodium and chloride reabsorption (microequivalents per minute) during the last third of gestation. This increase in sodium and chloride reabsorption was less than the increase in GFR (milliliters per minute) before 129 days but became higher than the rise of GFR (milliliters per minute) after 129 days of gestation.


Abruptio placentae and perinatal death: a prospective study. Abruptio placentae caused 3.96 perinatal deaths per 1,000 births in a large prospective study. Intrapartum but not prepartum maternal hypertension was observed in the fatal cases. Decidual necrosis at the placental margin and large placental infarcts were the most characteristic placental abnormalities. The decidual necrosis was correlated with maternal cigarette smoking and low pregnancy weight gains in the abruption placentae cases. The fetuses and neonates who died had a pattern of growth retardation  characteristic of antenatal undernutrition, indicating that poor maternal nutrition during pregnancy may have contributed to the genesis of the abruptio placentae.


Oral contraceptives and cervical carcinoma. In a case-control study, 689 consecutive patients with cervical carcinoma were studied for their use of oral contraceptives. The control patients were matched for age, ethnic origin, age at first pregnancy, age at first coitus, and socioeconomic status. There was no significant difference between case and control subjects in the duration or oral contraceptive use, the type of estrogen used, or the years in which oral contraceptives were used. The mean duration of oral contraceptive use was 30.9 months by the case subjects and 30.2 months by the control subjects.


Effect of progesterone and estradiol-17beta on nucleic acid synthesis in vitro in carcinoma of the endometrium. Nucleic acid synthesis was studied in 26 tumor specimens, during a one-hour in vitro incubation with the addition of progesterone and estradiol-17beta. On the response scale used, deoxyribonucleic acid and ribonucleic acid synthesis decreased linearly as the logarithmic concentration of either hormone increased. Inhibition of nucleic acid synthesis was highly significant (P less than 0.001) at 80 microgram per milliliter of progesterone and at 40 microgram per milliliter of estradiol. No evidence of synergism was found when the two hormones were combined at these concentrations. In Grade I and II tumors, the effect when both hormones were combined approximated the sum of effects of the individual hormones. In Grade III tumors, little difference was seen between treatment groups.


Some observations on the value of endocervical curettage performed as an integral part of colposcopic examination of patients with abnormal cervical cytology. A total of 259 patients underwent endocervical curettage as an integral part of colposcopic examination of patients with abnormal cervical cytology. The transformation zone was entirely visualized in 140 patients (54.1 per cent), and, in 8.6 per cent of this group, the endocervical curettings were abnormal. On no occasion did the endocervical curettage harbor the worst lesion when compared to the histology of the ectocervical biopsy, cone biopsy, and hysterectomy specimens. In 117 patients (45.2 per cent), the transformation zone could not be visualized in its entirety, and in 57.3 per cent the endocervical curettings were abnormal. In one patient of this group invasive carcinoma was present in the endocervical curettage, and in another patient invasive carcinoma was present in both the ectocervical biopsy and the endocervical curettage. Thus, when the entire transformation zone is not visualized in its entirety or at all, endocervical curettage appears to be of value since a frank invasive carcinoma may be diagnosed and a cone biopsy avoided.


A direct radioimmunoassay for estriol-16-glucuronide in urine for monitoring pregnancy and induction of ovulation. Antibodies to estriol-16alpha-[beta-D-glucuronide] were raised in sheep with the use of keyhold limpet hemocyanin and bovine serum albumin conjugates of estriol-16alpha-[beta-D-glucuronide]. A simple, rapid method is presented for direct radioimmunoassay of estriol-16alpha-[beta-D-glucuronide] in urine with dextran-coated charcoal used for separation of free from bound and deionized water used for dilutions. The method is thrifty in its use of reagents. The assay has been evaluated in the pregnancy range, and the sensitivity has been extended into the range necessary for monitoring induction of ovulation with Pergonal.


Abdominal wound dehiscence.

Abdominal wound dehiscence. Abdominal wound dehiscence is a surgical complication with a high morbidity rate but which is associated with predictable and preventable factors. During a 10 year period (1966 to 1975) at the New York Lying-In Hospital, 70 cases were found on the obstetric-gynecologic service, and these cases were analyzed to see why dehiscence remains a problem. Those factors contributing to dehiscence include obesity, pre-existing pulmonary and cardiovascular problems, vertical incisions, the triad of ileus, vomiting, and coughing, and, to a lesser extent, hypoproteinemia, fluid and electrolyte imbalance, and wound infection. The incidence of abdominal wound dehiscence would be much lower if high-risk patients were identified, adequate pulmonary toilet was used, ileus was promptly treated with abdominal decompression, and strict attention was paid to electrolyte and protein balance in the pre- and post-operative period. The management of abdominal wound dehiscence is also discussed.


Plasma concentrations of four pregnancy proteins in complications of pregnancy. Toxemia of pregnancy was associated with an elevation of the pregnancy-associated plasma protein (PAPP)-A concentration, as compared to the level in normal pregnancy in the last month of gestation. The other pregnancy proteins measured were not altered in toxemia. In twin pregnancies, the PAPP-A, PAPP-C, and human placental lactogen levels were all increased, particularly PAPP-A. On the other hand, pregnancy zone protein was not affected by twinning. Pregnancy with diabetes showed normal levels of these proteins.


Tactile sensitivity: development of a behavioral responses checklist. Tactile defensiveness or sensitivity to being touched is a phenomenon observed by therapists during clinical testing and is reported based only on subjective data. The purpose of this study was to develop a more objective means of identifying this phenomenon. Videotaped observations of five-year-old boys being administered the Southern California Kinesthesia and Tactile Perception Test battery were used to identify behavioral reactions indicative of sensitivity to tactile stimulation. The population tested for a wide range of behaviors included hyperactive and normal five-year-old boys. These reactions were defined and categorized into a checklist of tactile-sensitive behaviroal responses. This checklist was then used on videotapes of 10 five-year-old boys by two raters to establish a measure of the reliability of this method of observing and recording behaviors. A reliability of .89 agreement with consensus was reached. These behavioral categories offer objective guides in identifying children with tactile defensiveness or sensitivity to tactile stimulation.


Cluster analyses of measures of sensory integration. Cluster analyses of intercorrelation of scores on tests of sensory integrative, language, auditory, intellectual, and academic tests administered to young learning-disabled school children demonstrated a close relationship between academic achievement, the right ear score on dichotic listening, language expression, and auditory memory. Visual perception tests and the Auditory Association sub-test of the Illinois Test of Psycholinguistic Abilities showed a close association with IQ. Others associations were consistent with the view that when the two cerebral hemispheres do not corroborate, both hemispheres tend to develop similar motor and language functions. Analyses of the intercorrelation of scores on the sensory integration, auditory, and language tests resulted in four major factors: auditory-language functions, postural-ocular reactions, eye-hand coordination, and somatosensory and motor planning or praxis. A fifth factor, visual perception, contributed less to the final factor structure.


Use of videotape in occupational therapy. The use and production of videotapes in occupational therapy are expected to increase in the future. A survey of 54 occupational therapy curricula and 59 hospital-clinics showed that 71 percent of the respondents use videotapes. Of that group, 70 percent produce videotapes for occupational therapy. Forty-six percent of the producers of occupational therapy videotapes make them available to others. Ninety-two percent of the respondents indicated a need for reviews of films and videotapes pertinent to occupational therapy, either in a directory--or a directory, with monthly reviews of new materials in the Occupational Therapy Newspaper or AJOT. A listing of subject areas most needed in a videotape format was also compiled.


A psychogeriatric activity group in a rural community. Three senior students in occupational therapy and a faculty member collaborated with a community mental health center in implementing and conducting an Outreach Activity Group for socially isolated, psychogeriatric clients residing in an outlying rural community. The students gained experience in five areas: learning the structure, functions, and funding of a community program; identifying the role and function of occupational therapy in community-based mental health; making use of administrative and consultative role functions; leading a group; and, with other health professionals, identifying ways to lessen the problems faced by the psychogeriatric client in the community. The group was helpful in maintaining the psychogeriatric client in the community by promoting self-esteem, self-expression, new interests, constructive use of leisure time, reality testing, interpersonal relationships, and perceptual motor stimulation.


Level I field placement at a federal correctional institution. Two senior occupational therapy students at Eastern Michigan University were assigned during consecutive semesters to a Level I field placement at a Federal correctional institution and were supervised by a faculty member. Each student led a group of men in a life planning and work readjustment program. The program development, implementation, and evaluation of the experience are discussed here.


The health systems agency: a new bureaucracy. A Federal law signed by President Ford in 1975 (PL 93-641) mandates the establishment of Health Systems Agencies across the country. The major intent of the law is to provide local direction and control of health care planning. Each Agency shall have a professional staff under the aegis of a board of directors composed of a majority of consumers and a minority of providers. Data identifying health care needs shall be translated into a Health Systems Plan, which is a statement of goals for each Agency; an Annual Implementation Plan shall be developed as a statement of objectives, projects, and strategies requisite to achieving the Health Systems Plan. The concept of the Health Systems Agency has correlate state and federal bureaucratic strata to facilitate health care planning coordination.


Charles F. Prentice Memorial Lecture--1976. Optometry curriculum patterns in Europe. The education and training of optometrists--more appropriately, ophthalmic opticians--in the western countries of the European continent differ in content and amount from that found in English-speaking countries, particularly the U. S. Current curriculum patterns for 12 European countries are presented. Formalized basic education before professional training averages 9.4 academic years; formalized course work, identified with curricula of schools of optics and optometry, averages 2.8 academic years; and required apprenticeship time averages about 2 years.


Oxygen tension under a hard, gas-permeable contact lens. Oxygen tension under a hard, gas-permeable contact lens is calculated. The gas permeability of the lens is taken from the engineering literature and is shown to be 10 times smaller than claimed in the optometric literature. The engineering data are supported by new measurements of gas permeability. Calculations using the new data show that the oxygen tension under the lens is at the lower end of the range of acceptable values.


Rotation of spherical nonprism and prism-ballast hydrogel contact lenses on toric corneas. Six subjects were fitted binocularly with both nonprism and prism-ballast spherical HydrocurveTM contact lenses to evaluate lens rotation on toric corneas. The 1/2 delta and the 1 delta lenses rotated significantly less than the equivalent nonprism lenses. For 11 of 12 eyes, 1/2 delta was sufficient to stabilize the lens.


Border enhancement as an index of contact lens performance. In simultaneous border contrast enhancement, a border formed by an abrupt luminance discontinuity is perceptually enhanced on the bright side by a band of greater brightness and on the dark side by a band of greater darkness. The width of these perceived bands is very sensitive to small changes in the retinal image quality. This study explored the effect of contact lenses of varying steepness on the border enhancement spread. It was found that, over time, the effect of a contact lens on this spread generates a characteristic function. Furthermore, certain features of this function reflect the degree of steepness of the contact lens. It is suggested that the most important factors determining this function are tear flow and scatter-producing corneal edema.


Methods of tinting Soflens contact lenses. Different dyes were used to tint Soflens contact lenses. The light transmission of each lens was measured before and after tinting and after asepticizing it in fresh saline from 1 to 15 times. Crystal violet was found to be the dye most stably retained within the lens after saline asepticizing. By asepticizing hydrophilic lenses in solutions of food coloring, we found that the amount of dye retained by a lens was not cumulative and the transmittance was maintained at approximately the original value. Tests of these tinted lenses for toxicity to animals or human subjects were not performed, nor did we ascertain whether these dyes affect the durability or hydrophilic and wetting properties of these lenses.


Validity of Pinckers' 100-Hue version of the Panel D-15. Fifteen normal and 18 red-green-deficient subjects were tested with the Farnsworth Dichotomous Test of color vision (Panel D-15) and with an alternative version of the dichotomous test consisting of selected color chips from the Farnsworth-Munsell 100-Hue Test. Results indicate that the 100-Hue version of the dichotomous test is equivalent to the standard Panel D-15 with respect to detecting and differentiating among the more severe red-green deficiencies. These results confirm A. Pinckers' previous suggestion that the 100-Hue Test contains the components necessary for a Farnsworth Panel D-15.


Ultrastructure in glomerulonephritis associated with cryoglobulinemia. A report of six cases and review of the literature. Renal tissue from 6 patients with glomerulonephritis associated with cryoglobulinemia was studied by light microscopy, immunofluorescence microscopy, and electron microscopy. Fibrillar deposits in glomerular capillaries were observed in electron micrographs in 4 of 6 patients. The ultrastructure of these deposits is compared with those in 6 previously reported cases, with the ultrastructure of the serum cryoprecipitates, and with fibrillar glomerular deposits in other glomerulonephritides. It is concluded that serum cryoprecipitates are structurally similar to glomerular deposits and that these fibrillar deposits are a frequent and possibly distinguishing morphologic feature of glomerulonephritis associated with cryoglobulinemia.


Beneficial effect of propranolol in a histologically appropriate model of postischemic acute renal failure. Acute renal failure caused in the rabbit by clamping one renal pedicle for 1 hour and removing the opposite kidney produced a histologic picture very similar to that observed in "hypotensive" acute renal failure in man. Intravenous infusion of propranolol, a drug which prevents renin release, at 1 mg/kg for 70 minutes beginning at time of pedicle clamping resulted in significantly lower serum creatinine in this model (2.8 +/- 0.2 mg% at 48 hours with propranolol versus 5.2 +/- 0.8 mg% without). Renin stimulation by dehydration or feeding a low-salt diet enhanced the difference between treated and untreated groups (2.6 +/- 0.4 mg% with propranolol versus 6.2 +/- 1.8 mg% without, after dehydration; 3.5 +/- 1.0 mg% with propranolol versus 7.6 +/- 1.4 mg% without, after low-salt diet).Suppression of renin production by saline feeding eliminated propranolol's beneficial effect (5.6 +/- 0.9 mg% with propranolol versus 4.0 +/- 0.6 mg% without). In rabbits with a normal food and water intake, renal denervation using phenol also eliminated propranolol's effect (creatinine 8.6 +/- 1.4 mg% with propranolol versus 8.6 +/- 1.8 mg% without). In rabbits with intact kidneys, flow probe recording of renal blood flow showed a significantly higher blood flow immediately after unclamping in the propranolol-treated animals, and renal angiograms showed less vasoconstriction in this group after unclamping. In this model of acute renal failure, renal vasoconstriction plays an important role following the initial ischemic insult. Propranolol lessens the severity of this vasoconstriction and the resulting acute renal failure. Its probable action is interference with neurogenically stimulated renin release.


Tubulointerstitial nephritis and glomerulonephritis in Brown-Norway rats immunized with heterologous glomerular basement membrane. Tubulointerstitial nephritis and glomerulonephritis were produced in Brown-Norway rats (BN) by a single immunization with 2 mg of lyophilized bovine glomerular basement membrane. Tubulointerstitial nephritis was evident before glomerulonephritis. Antibody first bound to tubular basement membranes (TBM), and then the renal cortex was infiltrated with inflammatory cells. The TBM was split, and many renal tubules, especially proximal tubules, were destroyed. Approximately 14 days after the beginning of the tubular phase, antibody was observed to be bound to glomerular basement membranes (GBM) in linear fashion. There was epithelial and mesangial cell proliferation, splitting and reduplication of GBM, crescent formation, and glomerular scarring and atrophy.


Cellular swelling and irreversible myocardial injury. Effects of polyethylene glycol and mannitol in perfused rat hearts. Irreversible injury was produced in Langendorf-perfused rat hearts by 60 minutes of hypoxic, substrate-free perfusion at 37 C. Upon reoxygenation, hearts suddenly released large amounts of creatine phosphokinase (CPK) and over 60% of cells contained contraction bands and appeared irreversibly injured by light and electron microscopic  criteria. Ten percent polyethylene glycol (PEG) or mannitol (420 mOsmol/liter) prevented or reduced swelling of rat heart slices incubated in vitro in the cold or under anoxic conditions. Both PEG and mannitol inhibited oxygen-induced CPK release after 60 minutes of hypoxia. Cells from protected hearts contained contraction bands but remained structurally intact. The results of this study provide evidence that cell swelling may play an important role in the pathogenesis of oxygen-induced enzyme release and irreversible myocardial cell injury.


Localization in platelets of sodium 51Cr-chromate, 125I-antibody to whole membrane, and 3H-diisopropylfluorophosphate using electron microscopic autoradiography. Platelets from the rabbit and rat, respectively, were incubated with sodium 51Cr-chromate and 3H-diisopropylfluorophosphate (3H-DFP) in the same manner as for platelet survival studies. A third isotope, 125I, was incorporated into a labeled antibody raised against a partially purified pig platelet membrane fraction. The 51Cr label was found to be concentrated predominantly in the cytoplasm, with a marked degree of association with mitochondria, whereas the tritium label appeared to be largely confined to the periphery of the platelet, particularly in association with the open canalicular system. The 125I-labeled antibody showed a very marked association with the plasma membrane and the open canalicular system, suggesting a membrane-bound affinity.


Ultrastructural observations of the myenteric plexus of the pylorus in infantile hypertrophic pyloric stenosis. Myenteric plexuses and smooth muscle of the pylorus obtained by biopsy at pyloro myotomy in 5 infants with hypertrophic pyloric stenosis were studied by electron microscopy. Animal controls consisted of pyloruses from 2 infant and 2 adult rabbits and 2 adult rats. The principal findings in the plexuses of the patients were moderate numbers of variably sized, swollen degenerating axons that contained dense bodies, lamellated figures, vacuoles, granular or fibrillar material, and swollen mitochondria. The significance of this alteration in the etiology and pathogenesis of this disorder is not clear. Neurons in the plexuses showed no definite abnormalities. Although these findings do not confirm previous light microscopic observation of neuronal changes in the pyloric myenteric plexuses, they do not exclude a neurogenic mechanism for this disorder. The presence of small immature neurons and large mature neurons suggests that neuronal maturation and development in infantile hypertrophic pyloric stenosis are not impaired as previously reported. No ultrastructural changes were found in interstitial cells of the myenteric plexuses. Except for hypertrophy of the circular smooth muscle layers, no specific alterations were found in muscle fibers of the pylorus.


Effect of occlusion on large vessels. I. A study of the rat carotid artery. The effect of permanent occlusion on the carotid artery of the rat was studied by light and by electron microscopy. A segment between two ligatures was examined at times from 2 minutes to 1 year. Between 2 and 15 minutes after occlusion, the red blood cells adjacent to the wall formed radially arranged rouleaux; within 24 hours the endothelium disappeared, while platelets (despite the lack of flow) accumulated against the denuded elastica. This behavior of formed blood elements may have been the result of electric forces (injury potential). By 3 days, undifferentiated cells were found lining the elastica interna or free in the lumen; they apparently were derived from medial smooth muscle.In the media, by 3 days some smooth muscle cells had become necrotic, while "undifferentiated" cells appeared; strong circumstantial evidence suggested that these were smooth muscle cells which had lost their specific characteristics and had thus become dedifferentiated (a phenomenon also known to occur in striated muscle cells); by 1 month they had matured into smooth muscle, but the media from then on contained fewer cells and more collagen than normal.In the lumen, the undifferentiated cells also matured into typical smooth muscle cells from 15 days onward, while collagen and elastin appeared between them. After 1 month these cells began to accumulate droplets of fat, which thereafter increased in number (at 6 months they were associated with cholesterol clefts) and then declined. This accumulation of fat in smooth muscle cells (also seen in atherosclerosis) was interesting because it occurred in the absence of blood flow.


Role of parathyroid hormone in regulation of main calcium fluxes in rats. The effect of calcium deprivation on the various calcium fluxes was studied in growing rats either sham-operated (SHAM), thyroparathyroidectomized (TPTX), or thyroparathyroidectomized and supplemented with parathyroid hormone (PTH) (TPTX + PTH). In SHAM rats a decrease in the net absorption of calcium (Vna) has no influence on calcemia or on bone formation (Vo+), but leads to an increase in bone resorption (Vo-). In TPTX rats a decrease in Vna induces a decrease in calcemia and in Vo+ but still causes an increase in Vo-. The same is true in TPTX + PTH rats although all the variables measured are increased. In TPTX rats, both without and with PTH, a linear correlation exists between calcemia and Vo+ suggesting that calcemia influences bone formation. Furthermore, it appears that PTH is important in regulating bone turnover, but that the adaptation of Vo- to a change in Vna can occur in the absence or in the presence of a constant amount of this hormone. The mechanism of regulating this adaptation of bone resorption is still unknown.


Effects of nitroblue tetrazolium and vitamin E on platelet ultrastructure, aggregation, and secretion. All agents capable of triggering the platelet release reaction also stimulate prostaglandin biosynthesis in these cells. Information concerning the endoperoxides, thromboxanes, and more stable metabolites generated by the action of cyclooxygenase and lipoxygenase on arachidonic acid has accumulated rapidly, but little is known about the preliminary steps in the cleavage and preparation of arachidonic acid for insertion into the enzymatic pathways of prostaglandin synthesis. Studies in this laboratory have shown that the combination of nitroblue tetrazolium (NBT) and vitamin E which prevents oxygenation of arachidonic acid to a free radical also blocks platelet prostaglandin biosynthesis. The present study has evaluated the influence of NBT, vitamin E, and the combination of NBT and vitamin E on the fine structure and biochemistry of platelets during incubation, and the effects of these compounds on the aggregation and secretion of platelets stimulated by collagen, thrombin, epinephrine, and ADP. Results of the study demonstrate that NBT and vitamin E, rather than injuring platelets, appear to protect them during incubation. Together NBT and vitamin E blocked aggregation by epinephrine, collagen, and thrombin, but permitted a small first wave stimulated by ADP. Both ADP and thrombin induced shape change, pseudopod formation, and limited degrees of internal contraction in vitamin E-NBT-treated platelets, whereas epinephrine and collagen failed to significantly alter discoid form. This pattern of response to aggregating agents was identical to reactions observed in platelets pretreated with aspirin and indomethacin, both potent inhibitors of platelet prostaglandin synthesis. In addition, NBT-vitamin E virtually blocked the first wave of aggregation which is not affected by aspirin and indomethacin. The findings support the concept that conversion of arachidonic acid to an activated state is an important step in prostaglandin synthesis and that electron transfer or oxidation-reduction reactions are intimately involved in the development of platelet stickiness.


Activity of chloride in absorptive cells of Amphiuma small intestine. Double-barreled chloride-selective microelectrodes constructed by a new method have been used to determine intracellular chloride activity (aic1) in the absorptive cells of isolated, stripped proximal and distal segments of Amphiuma small intestine. Chloride was passively distributed across the mucosal membrane in fall and winter animals and aic1 is about 20 mM. In contrast summer animals actively accumulated chloride in both proximal and distal segments. Parallel measurements of intracellular chloride concentration (Cic1) reveal a very low apparent chloride activity coefficient (aic1/CiC1) indicating that all of the chloride is not free in the cytoplasm. The chloride activity in the bath immediately adjacent to the mucosa is higher than in the bulk solution.


Facilitation of hepatic uptake of phenol 3,6-dibromphthalein disulfonate by taurocholate. The influence of sodium taurocholate (TC) on the hepatic uptake of phenol 3,6-dibromphthalein disulfonate (dibromosulphophthalein, DBSP) was examined in the dog. Single injections of DBSP (7.5-83.3 mg-kg-1) were given intravenously and the initial velocity of uptake (V) of the dye was calculated from the plasma disappearance rate measured during the 1st 5 min. It was observed that: a) the initial velocity of uptake of DBSP increased with the dose (D) in a nonlinear way, a finding consistent with Michaelis-Menten kinetics; the maximal initial velocity of uptake (Vmax) was 7.5+/-1.0 (SD) mg-min-1-kg body wt-1, and the half-saturation constant (Kd) was 27.7+/-7.0 (SD) mg-kg-1; b) when a TC infusion was given prior to the DBSP injection, the initial disappearance of the dye was more rapid than in the absence of the bile acid; Vmax increased to 12.3+/-2.0 (SD) mg-min-1-kg-1 (P less than 0.001) and Kd increased to 50.3+/-12.8 (SD) mg-kg-1 (P less than 0.001). These results indicate that: 1) the uptake of DBSP by the liver cell is a saturable process; 2) TC increases both the Vmax, suggesting a facilitation of the uptake process, and the Kd, suggesting competition for a common site. This effect of TC on DBSP uptake is similar to the previously described effect of this bile salt on BSP excretion into bile and suggests an interaction of bile salts with the uptake process of dyes.


Longitudinal force and stress of rat's esophagus: age-related changes. Longitudinal force-length relationship of the rat esophagus was studied in vitro in three age groups: 1 mo, 3 mo, and 12 mo. The length of maximum force development (MFD) occurs at 1.4-1.5 times the in vivo length for all age groups. The active force developed at MFD increases markedly with age. The difference in the active forces in the 3-mo and 12-mo age groups is due to differences in cross section because the active stress of the esophagus in the longitudinal direction is approximately equal for the two age groups. The active stress in the 1-mo-old rats is lower than in the 3-mo-old rats, suggesting an increased contractility of the esophagus with age in this period of development.


Characteristics of accumulation of probenecid by rabbit kidney cortical slices. Probenecid was accumulated by renal tissue both under aerobic and anaerobic conditions. The aerobic uptake at a low medium concentration of probenecid was enhanced three- or fourfold by acetate, while metabolic inhibitors and organic anions like p-aminohippurate (PAH), phenol red, and other substituted phenolsulphonphthalein (PSP) dyes which undergo secretion had an inhibitory effect. Octanoate and succinate stimulated aerobic probenecid uptake at low medium concentrations, but inhibited transport of the drug at high levels. Studies on renal homogenates showed that the anaerobic uptake of probenecid is due to binding to tissue constituents. Binding characteristics of PSP dyes to phospholipid vesicles and a representative binding protein, human serum albumin, exhibited close similarity to that of binding to renal tissue. Hydrophobic compounds like octanoate and PSP dyes partially inhibited probenecid binding. In contrast, transport of probenecid was almost completely abolished by these substances and PAH at high medium concentrations. On the basis of the results presented in this paper, it is concluded that renal transport of probenecid occurs by the common organic anion transport system.


Mechanism of dopamine-induced diuresis in the dog. This study was undertaken to evaluate the effect of dopamine (D) on renal water excretion. Intravenous (i.v.) infusion of D (7.5 microgram/kg per min) was associated with a significant, reversible increase in free water excretion (CH2O) and a decrease in urinary osmolality (Uosmol). These changes, however, were associated with significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNaV). These increases could have been responsible for the diuretic response to D. To examine whether D has a direct effect on vasopressin (ADH) release, D was infused into one common carotid artery at a dose equal to one-fourth the i.v. dose. No effects on CH2O and Uosmol were observed. To examine whether D might have an antagonistic effect on ADH a single bolus of ADH (100 mU) was given to the same hypophysectomized dogs with and without D infusion. The antidiuretic response to ADH was the same, whether or not D was given concomitantly. The net changes in Uosmol and CH2O in response to ADH were not significantly different. Taken together, the present results provide no evidence for a direct effect of D on ADH release nor do they indicate an interference with the peripheral action of ADH. The dopamine-induced diuresis is probably the result of increased solute excretion. This, in turn, is the result of the combined effects of dopamine on increasing renal blood flow, GFR, and sodium excretion.


Ejection pressure and the diastolic left ventricular pressure-volume relation. The influence of ejection pressure (EP) on the left ventricular end-diastolic pressure-volume (P-V) relation was examined in 24 paced, isolated canine hearts. A pressure servo system was used to control EP and monitor ventricular volume. For any given contractile state EP was varied: a) by 10- to 20-mmHg increments and the steady-state P-V response observed at each EP level (method A); or b) by instantaneously attaining the isovolumic condition (PO) from a given EDV and examining the immediate P-V response (method B). With either method it was possible to alter the P-V relation; the maximum variation occurred when, for a given EDV or EDP, EP was raised from a value less than 50% of its corresponding peak isovolumic pressure to PO. For the EDP range 2-25 mmHg, the direction and total magnitude of change were: 1) an increase in EDV 1.3-9 ml was required to maintain EDP constant; and 2) for a constant EDV, EDP decreased an average 16.5%+/-1.2 SE (6-23.9%; P less than .02). The EDP decline observed with method B was immediate and reversible within several beats upon returning to the ejecting mode. Thus, under the conditions of this experiment the diastolic pressure-volume relation is a physiological variable dependent on ejection pressure.


42K exchange during myocardial ischemia. 42K exchange was studied before and after total ischemia in isolated, blood-perfused rabbit interventricular septa at 37 degrees C and 72 beats/min. Of 11 septa made ischemic for up to 45 min after 42K labeling to asymptotic values, 10 showed no decline in 42K as measured by tissue probe counts 5 min after reperfusion. Of these 10 septa, 7 showed a 1.4-14.2% increase in 42K counts on reperfusion. Three of four muscles reperfused after 60 min of ischemia showed progressive 42K losses. Of 14 septa previously labeled with 42K, 9 showed a parallel decrease in 42K-exchange rate constants as measured by tissue probe and effluent during washing out after 2-45 min of ischemia. In five other muscles a nonparallel decrease in rate constants as measured by tissue probe and effluent during washout indicated inhomogeneity of 45K exchange. These results indicated no persistent impairment in Na pump activity for 30-45 min of total ischemia. After ischemia for 45 min or less there was no consistent relationship between recovery of mechanical function and preservation of 42K content. After 60 min of ischemia, irreversible mechanical injury was associated with loss of tissue potassium.


Arteriolar reactive hyperemia: modification by inhibitors of prostaglandin synthesis. Several studies implicate endogenously synthesized prostaglandins in the mediation of reactive hyperemic responses in the coronary, renal, and skeletal muscle circulations. We sought additional evidence to involve locally released prostaglandins in the mediation of reactive hyperemia in skeletal muscle at the level of the microcirculation. The cremaster muscle of pentobarbital-anesthetized Wistar-strain rats was prepared for direct in vivo observation and measurement of postocclusive responses of single arterioles. Responses of individual arterioles were reproducible over a 3-h test period. The postocclusion increase in diameter and the duration of response were dependent upon the duration of the occlusion. Repetitive occlusions did not influence arteriolar responsiveness to vasoactive substances. Indomethacin and 5-8-11-14-eicosatetraynoic acid, inhibitors of prostaglandin synthesis, did not affect resting arteriolar diameters; however, both drugs decreased the maximum increase in diameter and duration of the vasodilator response following release of the arteriolar occlusion. These findings suggest that in this microcirculatory bed, prostaglandins contribute little to resting vascular tone; in contrast, temporary arteriolar occlusion elicits the local release of dilator prostaglandins which contribute to the reactive hyperemic response.


Anatomic response of canine hindlimb vasculature to chronic venous occlusion. Total limb (iliac) flow, small-vein pressure, and total small-vessel and venous resistances were measured in the fully dilated bed 2 h, 2 wk, and 8 wk after extensive ligation of veins. Values were compared to similar measurements in the contralateral unoccluded extremity. Wall thickness, lumen size and distensibility of noncollateral veins, and enlargement of collateral veins were evaluated 8 wk after venous ligation. Two hours after ligation, anatomic vascular resistance was twice normal, and venous resistance was increased sevenfold. Eight weeks later, total limb anatomic resistance had decreased to a value slightly less than normal, suggesting an "overcompensation" in anatomic resistance. Wall thickness of noncollateral veins was greater than normal at 8 wk postligation, and lumen size and distensibility were less than normal in spite of a return of supine venous pressure to normal levels.


Ventral root mapping of cardiac nerves in the canine using evoked potentials. The sympathetic efferent contribution of left ventral roots T2, T3, and T4 to some cardiac nerves was studied using evoked potentials in mongrel dogs anesthetized with sodium pentobarbital. Electrical stimulation of the ventral roots while recording evoked potentials from the sympathetic chain, anterior ansa subclavia, posterior ansa, ventrolateral cervical cardiac nerve, ventromedial cervical cardiac nerve, and the vagosympathetic trunk demonstrated that A-, B-, and C-type fibers exist in these efferent neural pathways. The range of conduction velocities observed was 0.7-104 m/s. T2 contributed the largest number of A-type fibers, and T2 and T3 contributed C-type fibers equally, while T4 had the least number of fibers coursing through the cardiac nerves.


Effect of arterial carbon dioxide on cerebral blood flow in ducks. The purpose of this study was to determine the effect of arterial PCO2 on blood flow to the avian brain. Cerebral blood flow was measured on curarized, artificially ventilated Pekin ducks by the rate at which intra-arterially injected xenon-133 was cleared from the duck's brain. A two-component clearance curve resulted: the blood flow calculated from the fast and slow components was similar to the blood flow to mammalian grey and white matter, respectively. Hypercapnia markedly increased the fast component of blood flow, whereas hypocapnia had no effect on this component. These effects were not due to changes in blood pressure, which was independent of arterial PCO2. Blood flow calculated from the slow component was independent of arterial PCO2. We conclude that the lack of response to hypocapnia may contribute to the exceptional tolerance of birds to high altitude by maintaining normal cerebral blood flow.


Effects of methylprednisolone on cardiac lymph in acute myocardial ischemia in dogs. It has been proposed that administration of pharmacologic doses of glucocorticoids may be beneficial in the setting of acute myocardial ischemia because of their ability to stabilize lysosomal membranes and thereby to prevent the leakage of proteolytic enzymes into the cytoplasm and interstitium. We collected cardiac lymph in anesthetized open-chest dogs in successive 2-h periods and used acid phosphatase as our marker lysosomal enzyme. In group 1 (n=5), we studied the effect of time alone. In these dogs, the total amount of acid phosphatase decreased (P less than 0.05). In group 2 (n=5), methylprednisolone, 30 mg/kg iv, was given. This drug did not change any variable we measured. Ligation of the circumflex coronary artery in group 3 (n=7), produced a significant increase (P less than 0.05) in the amount of acid phosphatase drained from the heart compared to group 1. In the dogs of group 4 (n=5), methylprednisolone did not reduce, and may have augmented, the total amount of acid phosphatase draining from the heart. Thus glucocorticoids do not appear to reduce the amount of acid phosphatase released by the ischemic myocardium into the cardiac lymph.


Effect of sex hormones on blood pressure and vascular connective tissue in castrated and noncastrated male rats. Aortic collagen and elastin were quantitated in three groups of castrated and two groups of noncastrated male rats treated by intramuscular injection for 3 wk with oil, testosterone, or estradiol. The greatest differences were found between the castrated rats receiving testosterone and those receiving estradiol, the estradiol-treated rats having significantly lower total collagen, percent collagen, total elastin, and collagen/elastin (C/E), and higher percent elastin than those rats receiving testosterone. In noncastrated rats, administration of estradiol resulted in significantly lower total collagen, percent collagen, total elastin, and C/E. Systolic blood pressure was highest in rats receiving testerone and lowest in rats receiving estradiol. It is concluded that 1) estradiol in the presence or absence of testosterone decreases total accumulation of vascular connective tissue and alters the proportions of collagen and elastin so that the vessel is more distensible, 2) testosterone has an opposite but less marked effect than estradiol on vascular connective tissue, and 3) estradiol and testosterone alter blood pressure in opposite directions in the male rat.


Role of fibrinopeptide B release: comparison of fibrins produced by thrombin and Ancrod. The gelation time, opacity, light scattering, and elastic moduli of human fibrin gels clotted in the presence of thrombin, Ancrod, and Reptilase have been compared. At low ionic strength lateral association to thick fibers is observed in all cases. At all ionic strengths thrombin fibrin forms thicker fibers than does Ancrod fibrin. We have demonstrated that an increase in the extent of lateral association is linked to an increase in its velocity and to a decrease in the gelation time. One may consider the removal of fibrinopeptide B to act as a switch: after it is removed fibrin assembles rapidly to thick fibers and gelation is fast; but when this peptide is still attached, there is a slow assembly of thin fibers, and gelation, especially of dilute fibrin, is delayed. We believe that this delay is critical for the complete digestion by plasmin of fibrin formed during in vivo defibrination with  Ancrod and of fibrin produced by very small amounts of thrombin (which would still contain fibrinopeptide B), and that slow release of fibrinopeptide B is part of a control mechanism for the regulation of fibrin formation and the prevention of intravascular coagulation.


Cardiopulmonary baroreflexes: left ventricular effects. Systemic vascular resistance of dogs perfused at constant arterial pressure by a pump oxygenator was used as a measure of left ventricular baroreflexes initiated by imposing pressure changes on the beating, as well as on the fibrillating, ventricle. In the unloaded beating heart mean left atrial and systolic ventricular pressures averaged 0.3 and 24 mmHg, respectively. Afterloads and preloads that increased systolic pressure to 63 mmHg while raising mean atrial pressures to 3.3 and 1.7 mmHg, respectively, had no effect on resistance. However, pressurization of the fibrillating ventricle caused vasodepressor responses proportional to the stimulus. The ventricular baroreflex had a significantly lower sensitivity and higher threshold than the vasodepressor reflex observed when simultaneously pressurizing the fibrillating ventricle, beating atrium, and lung vessels. On the basis of wall tension, the results are consistent with other reports that have shown ventricular baroreflexes to be initiated by systolic pressure in the range 100-150 mmHg, but not by diastolic pressure in the range 10-20 mmHg. A more sensitive reflex, able to respond to changes of ventricular filling pressure, arises from the left atrium and pulmonary veins.


Transmural myocardial perfusion during restricted coronary inflow in the awake dog. Phasic coronary flow and transmural myocardial perfusion were studied during coronary artery constriction in 10 dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional blood flow was estimated using left atrial injections of radionuclide-labeled microspheres 9 micron in diameter. During control conditions, 14+/-0.7% of coronary flow occurred in systole and subendocardial (endo) flow exceeded subepicardial (epi) flow in the region of the posterior papillary muscle (endo/epi=1.16). Immediately following partial inflation of the occluder to reduce coronary inflow 39+/-3%, systolic flow was unchanged while diastolic flow fell 42+/-3%, thereby increasing the portion of flow in systole to 22+/-1.4%. At this time blood flow was reduced nearly uniformly across the wall of the left ventricle. When coronary constriction was maintained for 30 s, an additional shift of flow from diastole to systole occurred (systolic flow=29+/-2.3% of total inflow), and transmural perfusion was redistributed from subendocardium to subepicardium (endo/epi=0.37). This redistribution of flow was accompanied by a fall in coronary pressure distal to the occluder, indicating vasodilation of the distal coronary vasculature.


Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow. Acute denervation of the liver did not result in changes of oxygen uptake or hemodynamics in the intact liver of the cat. Stimulation of the hepatic nerves resulted in a marked reduction of vascular conductance of the hepatic artery and portal vein (intrahepatic) resulting in almost complete cessation of arterial flow and increased portal blood pressure. The hepatic artery showed a more complete escape from the neurogenic vasoconstriction than did the portal vein. During the stable "escape phase" oxygen delivery was 86% of control, but hepatic extraction of oxygen increased so that oxygen uptake was not altered from control values. The return of oxygen consumption to normal during nerve stimulation suggests that redistribution of hepatic blood flow did not occur. In spite of arterial and portal venous blood pressure changes and changes in gut conductance, oxygen extraction of the gut did not change.


Spinal interneurons in the baroreceptor reflex arc. The zona intermedia of the cat thoracic spinal cord was explored with metal microelectrodes in an attempt to locate interneurons within the pathway that mediates the spinal component of baroreceptor-induced sympathoinhibition. Twenty-nine neurons whose discharges were interrupted during occlusion of the common carotid arteries were found in the vicinity of the intermediomedial nucleus (IMM). The spontaneous discharges of 10 of these units were correlated in time with the R wave of the ECG. The pattern of R-wave locking of spinal unitary discharge was similar to that for some neurons in the nucleus of the tractus solitarius (NTS; primary site of baroreceptor fiber termination). In addition, spinal units, whose discharges were interrupted during carotid artery occlusion, were activated by stimulation of depressor sites in NTS. These observations suggest that bulbospinal fibers of the baroreceptor reflex arc terminate on and excite interneurons in the vicinity of IMM. It is postulated that these neurons directly inhibit components of sympathoexcitatory pathways located in  the intermediolateral spinal nucleus. Furthermore, it was demonstrated that the inhibitory interneurons receive auxiliary input from sympathetic afferents in the inferior cardiac nerve.


Perfusion rates and the transfer of water across isolated guinea pig placenta. The transfer of tritiated water across the isolated, artificially perfused guinea pig placenta was the subject of 21 experiments. The observed relationship between the flow rates and the relative transfer of water cannot be explained by a concurrent or pool-flow system. If the direction of the fetal flow is reversed, the rate of transfer is lowered. It may be concluded, that the decrease is a result of a change from a nonideal countercurrent flow system to a nonideal concurrent system. This conclusion, however, holds only if all other parameters that determine the exchange as well remain unaffected. In the range of flows investigated, the transfer of water is flow limited.


Effect of prostaglandins on macromolecular transport from blood to lymph in the dog. The effect of various prostaglandins on hindlimb lymph flow and macromolecular transport was studied in dogs anesthetized with pentobarbital sodium. Lymph obtained by cannulating the popliteal lymphatics was collected at 30-min intervals and analyzed for protein and exogenously administered dextran (Dextran 110). Arterial blood was obtained at the midpoint of each collection period and similarly analyzed. Prostaglandins (E1, E2, F2alpha, and A2), the vehicle and histamine were injected subcutaneously into the paw of the dog. Prostaglandins slightly increased lymph flow (L') but the lymph-to-plasma concentration ratios (R) for total protein (T) and Dextran 110 (D) decreased. Permeability surface area products (PS) were not altered. The sieving ratios (RD/RT) were substantially less than 1 and were not altered by prostaglandins. These results indicate that selective permeability of the capillary is not impaired by prostaglandins. Timing sequences and dose-response relations were also completed for prostaglandins by subcutaneous testing in dogs injected with Evans blue (T-1824). Leakage of the T-1824-albumin complex occurred when large amounts (migrogram) of prostaglandins were administered, and the response appeared to be short lived (less than 30 min). While the prostaglandins possess vasoactive properties, as demonstrated by an increased lymph flow, they do not alter the restrictive transport of large molecules.


Interaction of aortic pressure and left ventricular end-diastolic pressure in the dog. Fiber length (preload) is an important determinant of left ventricular performance. Mean aortic blood pressure also influences ventricular performance. The present study was undertaken to examine the influence of mean aortic pressure on the fiber length-ventricular performance relationship. Fifteen anesthetized, adrenergically blocked dogs were studied on right-heart bypass at constant heart rate and coronary blood flow. An increase in mean aortic pressure permitted a greater improvement in performance as evaluated by stroke work for a given increase in left ventricular end-diastolic pressure. A given increase in mean aortic pressure at a constant stroke volume produced a greater rise in stroke work over intermediate ranges of left ventricular end-diastolic pressure than occurred with higher or lower left ventricular end-diastolic pressure. Thus, the degree of afterload-induced performance improvement depended on the magnitude of the preload. External circumference-left ventricular end-diastolic pressure data suggested a possible relationship between isovolumic systolic circumferential expansion and the improvement of ventricular performance at higher mean aortic pressures.


Capillary supply of skeletal muscle fibers in untrained and endurance-trained men. Muscle fiber diameters and numbers of capillaries per fiber, per square millimeter, and around each fiber were determined in needle biopsies from the lateral part of the quadriceps muscle of 23 young men. Twelve subjects were untrained (UT) and eleven were endurance-trained (ET) athletes. Average values for maximal oxygen uptake were 51.3 (UT) and 72.0 ml/kg-min (ET). Mean fiber diameters were not significantly different in the two groups (48.8 and 49.1 micron). The capillaries per fiber ratios were 1.77+/-0.10 and 2.49+/-0.08 (mean+/-SE) in the UT and ET groups, respectively. The numbers of capillaries around each fiber were 4.43+/-0.19 (UT) and 5.87+/-0.18 (ET). The numbers of capillaries per mm2 were 585+/-40 (UT) and 821+/-28 (ET). Fiber diameters were 28% smaller in ultrathin than in fresh-frozen sections from the same biopsies. After correction for this difference, the numbers of capillaries per mm2 were 305 and 425 in the UT and ET, respectively. The capillaries per fiber ratio increased with increasing fiber diameter, but not sufficiently to maintain the number of capillaries per mm2. Fibers containing many mitochondria are surrounded by more capillaries than fibers with few mitochondria.


Physiological characteristics of skeletal muscles of dogs and cats. Our purpose was to determine if physiological characteristics of skeletal muscles of dogs and cats are related to their histochemical and biochemical characteristics. Maximum oxygen consumption (VO2max) and blood flow (Q) at VO2max were determined for in situ muscles of dogs and cats. Compared to cat muscles, dog muscles per unit mass had higher succinate oxidase activities, VO2max's, and Q's at VO2max's. There are positive relationships between Q at VO2max and VO2max and between VO2max and succinate oxidase activity. The higher VO2max's and succinate oxidase activities of dog muscles are consistent with the presence in these muscles of only slow-twitch fatique-resistant fibers and fast-twitch fatique-resistant fibers, whereas up to 50% of the fibers found in cat muscles are fast-twitch fatiqable. Capillary-to-fiber ratios are 2.40-2.97 for dog muscles compared to 2.17-2.84 for cat muscles. Thus the two- to threefold higher Q at VO2max for dog muscles compared to cat muscles is not due to a greater number of capillaries.


Effects of temperature on some membrane characteristics of carotid body cells. Excised cat carotid bodies and nerves were placed in a Lucite chamber through which saline flowed at different temperatures. Action potentials were recorded with a suction electrode. Glomus cells were impaled with microelectrodes and identified by ejecting Procion navy blue from the micropipette. Membrane potentials (MP) averaged 20 mV and input resistances (R0), 40 Momega. Cooling induced depolarization and decreased R0. This effect had a reversal potential of about -6 mV. [K+]0 did not affect MP, R0, or cooling effects. Lack of sodium increased MP, R0, and depressed cooling effects. Low chloride had opposite effects. Ca2+ and Mg2+ influenced MP and R0 but had little effects on temperature actions. Ouabain decreased MP and R0. Results indicate that glomus cells are exquisitely sensitive to temperature changes; their MP and R0 increase with high temperatures and decrease when temperature is lowered. These effects are mostly dependent on the external concentration of Cl- and Na+. Glomus cells may be the site of the intense metabolism of this tissue and thus contribute to the generation of chemosensory impulses.


Mechanical properties of taenia coli smooth muscle in spontaneous contraction. The following mechanical tests have been performed on spontaneously contracting taenia coli: isometric step stretch, isotonic step loading, and length-tension. Passive stress-strain tests have also been done. Information on spontaneous contraction was more readily obtained in isometric tests. In length-tension tests, each isometric contraction was analyzed on a phase plane which is a representation of muscle stress, sigma(t), versus the rate of change of stress, sigma(t). The curve in the phase plane provided parameters for describing spontaneous contraction as a function of muscle length, L. The maximum active stress in a cycle of spontaneous contraction, S(L)max, and the maximum rate of increasing active stress, [S(L)]max, were shown to depend on L in the same way. Both parameters attain a maximum value (upper bound) at the same muscle length, Lmax. When L less than Lmax, the minimum stress in a spontaneous contraction, sigma(l)min, is negligible. If L greater than Lmax, sigma(L)min increases nonlinearly and is equal to the passive stress, tau(L), in an epinephrine-relaxed muscle. The results show that the ratio of [S(L)]max to S(L)max, eta(L), is constant for a physiological range of muscle length. This suggests that eta(L) may be used as an index of contractility for taenia coli.


Application of a solid membrane ion-selective electrode to in vivo measurements. A solid membrane electrode containing a highly selective ion-complexing agent immobilized in a polymer membrane is applied to measurements in vivo from the surface of an organ. For the measurements reported here, an ion-complexing agent selective for potassium is incorporated in a silicone rubber membrane and applied to measure ion changes in the brain. Comparison is made to the measurements recorded with an ion-selective microelectrode in the cortical tissue. The surface electrode compares favorably with the microelectrode in terms of amplitude of response and response time for the changes seen in the phenomenon of cortical spreading depression of Leao. The methods reported here are amenable to a selection of ion measurements by incorporation of a suitable ion exchanger in a polymer membrane. Extracellular ion activity is monitored in the anesthetized animal by holding the electrode in a balanced suspension which provides a light, flexible contact to the organ of interest. In the unanesthetized animal, when recording from the brain, the electrode is fixed in a skull-implanted cannula.


A comparison of effect of insulin on hepatic metabolites, gluconeogenesis, and ketogenesis. In 12-h fasted rats given tryptophan, insulin decreased the hepatic content of alanine and the three precursors of oxalacetate-malate, citrate, and aspartate-while elevating hepatic pyruvate. These changes are consistent with suppression of the pyruvate carboxylase step. Animals fasted for 24 h lose the effect on oxalacetate precursors, and this correlates with a loss of suppression of hepatic ketones. The decrease in hepatic alanine and oxalacetate precursors is more sensitive than the blood sugar. However, the conversion of labeled lactate to glucose is not inhibited by insulin in 12-h fasted animals. (+)-Decanoylcarnitine also produces a decrease in oxalacetate precursors comparable to insulin and a lowering of the blood sugar. However, in fasted animals not given tryptophan it does not alter the blood sugar. Therefore, in tryptophan-treated animals alterations of fatty acid oxidation by insulin or (+)-decanoylcarnitine produce a fall in oxalacetate precursors consistent with inhibition of pyruvate carboxylase but this does not equate with overall suppression of gluconeogenesis by either of these agents in the absence of tryptophan.


A comparison of intrinsic nerve supplies of two muscular layers of duodenum. The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the direction of the oral-caudal axis were called longitudinal strips, and those cut at 90 degrees to that axis were called circular strips. Each muscle strip was stimulated with trains of electrical rectangular pulses (10 Hz, 50-70 V, 0.5 ms). In the longitudinal strips, electrical field stimulation caused contraction, and this contraction was abolished by atropine, 10(-7) M. In the circular strips, electrical field stimulation caused relaxation. This relaxation was abolished by tetrodotoxin, 10(-7) M, but it was not affected by antagonists to adrenergic and cholinergic transmission, nor by some gastrointestinal hormones. Reserpinization of the opossums or alteration of the frequencies of electrical field stimulation from 0.1-50 Hz did not affect or alter the relaxation of the circular strips or the contraction of the longitudinal strips. These findings suggest that the longitudinal muscle is dominated by an excitatory cholinergic innervation, and the circular muscle is dominated by a nonadrenergic, noncholinergic inhibitory innervation.


Episodic secretion of arginine vasopressin. The plasma arginine vasopressin (pAVP) response to osmotic stimulation was studied in dogs and sheep by sampling at frequent intervals during steady-state dehydration and during water diuresis. Frequent sampling also was conducted after continuous infusion or bolus injection of 5 or 20 g/100 ml NaCl. A pulsatile pattern of pAVP was observed after such infusions or injections and in some animals after water deprivation. This pattern was not seen after water loading or in mildly dehydrated animals. The short term changes in pAVP during continuous infusion of 5 g/100 ml NaCl could not be correlated with variations in plasma tonicity. Rather, they appeared to reflect discontinuous hypothalamic posterior pituitary release of AVP. Thirst was evoked by a lower dose of 5 g/100 ml NaCl than was required for consistent stimulation of pAVP release, and the thirst response frequently was observed prior to the peak AVP response after bolus injection of 5 and 20 g/100 ml NaCl.


Log linear relationship between plasma arginine vasopressin and plasma osmolality. The integrated plasma arginine vasopressin concentration (IpAVP) was determined by pooling the results of single samples collected every 3 min for 0.5 h in dehydrated, randomly hydrated, and water-loaded sheep. A linear relationship was observed between the log of the integrated AVP concentration and plasma osmolality. This relationship was tested by the bolus injection of 20 g/100 ml NaCl to both water-loaded and randomly hydrated sheep. The rise in the log of IpAVP divided by the rise in plasma osmolality was similar in both groups (P greater than 0.5) and was superimposable upon the regression line derived from steady-state observations. The data would suggest that AVP is released as an exponential function of plasma osmolality rather than as a threshold phenomenon.


Transport of purine nucleotides and nucleosides by in vitro rabbit ileum. The kinetics of [14C]ATP and [14C]adenosine entry into rabbit ileum were measured using 1-min mucosal exposures. ATP influx was the sum of a linear (P = 1.02 X 10(-3) cm/min) and nonlinear component (Jm = 4.07 nmol/min cm2, Km = 0.31 mM). Adenosine yielded quantitatively similar results. The kinetics of [gamma-32P]ATP entry were only linear (P = 0.55 X 10(-3) cm/min). These data indicate that at least 85% of the terminal phosphate of ATP is hydrolyzed during transport. Inhibitory measurements indicate that ring-labeled ATP and adenosine compete for a common entry path; however, adenosine does not inhibit the saturable component of [14C]ATP to the degree expected of a simple carrier-mediated system. Adenosine (5 mM) produced no inhibition of [gamma-32P]ATP (0.1-1.0 mM) entry. Measurement of hydrolysis during incubation indicates a negligible fraction of uptake results from labeled adenosine released into the bulk solution. Hydrolysis of ATP followed by a preferred uptake of the adenosine released at the membrane surface probably accounts for most of the observed transport. [14C]ATP entry depended neither on [Na+], [Mg2+], nor [Ca2+] of the bulk solution. Structural requirements for the saturable pathway were also investigated. Autoradiography of [3H]ATP confirmed that the labeled material entered the epithelial cells and that uptake was nonuniform among cells.


Mechanism of angiotensin II-induced proteinuria in the rat. To investigate the mechanism(s) of angiotensin II-induced proteinuria, polydisperse [3H]dextran (D) (radius = 18-42 A) was infused into seven Munich-Wistar rats before and during intravenous infusion of angiotensin II (AII), 0.35 microgram/kg per min. During AII infusion, UprotV rose approximately twofold, and the fractional clearances of D [(U/P)D/(U/P)In] increased significantly for dextrans with radii greater than 22 A. Single nephron filtration fraction increased, due to a measured rise in the glomerular transcapillary hydraulic pressure difference from 34 to 43 mmHg. Near constancy of single nephron glomerular filtration rate resulted, however, from the offsetting effect of a decrease in glomerular plasma flow rate from 83 to 60 nl/min. These measured hemodynamic changes were found, by the use of pore theory, to account to a large extent for the measured increases in (U/P)D/(U/P)In. In seven other rats, fractional clearances of polyanionic dex-ran sulfate (a more reliable marker of albumin filtration than D) were also found to increase significantly with AII, suggesting that the proteinuria induced by AII can be explained, in large part, by hemodynamic factors.


Parasympathetic control of Na, K transport in perfused submaxillary duct of the rat. The effects of stimulating the parasympathetic innervation to rat submaxillary gland on ductal transport of Na, K, water, and transepithelial PD, were tested in the main excretory duct during perfusion through its lumen. During nerve stimulation, transepithelial PD was consistently decreased, usually by about 15 mV, and this decrease could be blocked by atropine but not by adrenergic blocking agents. Net flux of Na, K, or water was not significantly changed during stimulation. One-way flux of Na from the lumen also was unaffected. The decrease in PD during stimulation was not affected by substituting isethionate for Cl or increasing [K] in the luminal perfusion medium. It is concluded that parasympathetic effects are exerted on the ductal cells, but that these probably do not involve conductance changes at the luminal membrane.


Response of phosphate transport to parathyroid hormone in segments of rabbit nephron. The effects of bovine parathyroid hormone (PTH) on phosphate transport were examined in proximal convoluted tubules, proximal straight tubules, and cortical collecting ducts isolated from the rabbit kidney. The lumen-to-bath flux of phosphate (JlbPO4) and the bath-to-lumen flux (JblPO4) were measured simultaneously with [33P]phosphate and [32P]phosphate. In the proximal convoluted segments perfused with an ultrafiltrate of normal serum, PTH reduced the fluid absorption rate from 1.21 +/- 0.10 to 0.60 nl/mm-min but did not affect JlbPO4, which averaged 5.45 +/- 0.97 pmol/mm-min, or JblPO4, which was 0.50 +/- 0.08 pmol/mm-min. During perfusion with low bicarbonate-high chloride fluids at pH 7.4, the PTH-induced changes in fluid absorption were eliminated but no change occurred in phosphate transport. On the other hand in proximal straight segments JlbP04 was lower at 2.64 +/- 0.41 pmol/mm-min and was directly inhibited by PTH to 1.90 +/- 0.34 pmol/mm-min (P less than 0.001). Net phosphate transport was not observed in cortical collecting ducts in the presence or absence of PTH. These data suggest that phosphate absorption in the proximal tubule involves more than one transport system, that the effects of PTH on fluid absorption are not interdependent with the effects on phosphate transport, and that the proximal straight tubule appears to be an important site of PTH-sensitive phosphate transport.


Effect of catecholamines on tubular function in the isolated perfused rat kidney. Addition of norepinephrine or epinephrine to the isolated rat kidney perfused at constant pressure resulted in an increase in sodium reabsorption and the excretion of a dilute urine with an increase in free water clearance. Vasopressin reversed the fall in urinary osmolarity but not the diminution in sodium excretion. The urinary changes produced by catecholamines were blocked by propranolol but not by phenoxybenzamine, suggesting that they were mediated, at least in part, by beta receptors. Similar though less pronounced changes in sodium excretion and urinary osmolarity were produced by isoproterenol and phenylephrine, while the combination of these drugs induced marked dilution of the urine. The results suggest that circulating catecholamines or adrenergic nerves innervating the kidney directly influence renal tubular function and might, therefore, participate in the regulation of sodium and water excretion by the kidneys.


Effect of glycine and glucagon on glomerular filtration and renal metabolic rates. A rise in glomerular filtration rate (GFR) during saline infusion increases outer medullary more than cortical metabolic rate. To determine whether other GFR-increasing agents have a similar effect, renal metabolic rates were estimated by the heat-production technique during infusion of glycine or glucagon. Glycine and glucagon increased GFR by 17 +/- 2 and 32 +/- 2%, renal blood flow (RBF) by 34 and 21%, and outer medullary metabolic rate by 42 +/- 3 and 59 +/- 4%, respectively. Cortical metabolic rate rose by 7 +/- 1% during glucagon, and it increased by 29 +/- 2% during glycine infusion, suggesting a stimulation unrelated to sodium reabsorption. To determine whether glucagon influenced renal metabolism independent of its GFR-increasing effects, vasodilation was achieved by ureteral or suprarenal aortic constriction. Glucagon was without effect on RBF, GFR, and metabolic rate, but infusion of acetylcholine still raised RBF. We conclude that glucagon increases GFR by dilating vascular segments participating in autoregulation, and that energy-requiring NaCl reabsorption in the outer medulla is increased secondary to increased delivery of NaCl.


Renal extraction of glucagon in rats with normal and reduced renal function. To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.


Natriuresis after adrenal enucleation: effect of spironolactone and dexamethasone. After adrenal enucleation, rats have an impaired ability to excrete a salt load because of enhanced collecting duct reabsorption. This antinatriuretic effect, thought to be secondary to a mineralocorticoid-like substance secreted by the enucleate gland, can be reversed by treatment with spironolactone or dexamethasone. To define the renal mechanisms involved in this drug-induced natriuresis we have utilized clearance and micropuncture techniques in enucleate saline-expanded rats that were treated with either spironolactone (S) or dexamethasone (D), or were untreated (U). Sodium excretion was clearly increased after S, 13.9, and D, 19.3 mueq/min vs. u, 5.9 mueq/min. The mechanisms of this natriuresis, however, were dissimilar. Spironolactone-treated rats were not different from untreated rats except with regard to function beyond the superficial late distal tubule, where U rats reabsorbed over 50% of the delivered sodium. In the S group 38% of the excreted sodium was added along this tubular locus, 5.2% of the filtered sodium reaching the late distal tubule and 7.3% appearing in the urine. These data demonstrate that the natriuresis after S is secondary to the net addition of sodium beyond the superficial late distal tubule. Spironolactone may work by inhibiting a mineralocorticoid-like product of the enucleate gland and, thereby, eliminate the sodium-retaining effect of this product. The natriuresis after D, however, can be explained solely on the basis of a markedly increased filtered load of sodium traversing the nephron.


Relation of proteins, platelets, and gas nuclei in adhesion to a synthetic material. We report the result of exposing silicone rubber to washed pig platelet suspensions that contained on average 0.018 mg of proteins/ml in solutions. This protein content is sufficiently low to reasonably neglect the protein adhesion to the material. On comparing the measured platelet adhesion from the platelet suspensions with that from blood, we find that when the gas nuclei normally present in the surface roughness of the material are removed the number of adhering platelets is the same. Thus, in the absence of the gas nuclei, the proteins in blood plasma play a negligible role in the platelet adhesion. In contrast, when both the gas nuclei and proteins are present, the maximum platelet adhesion was observed. From this and the above observation, it appears the gas nuclei affect one or more of the proteins, and this brings about an increased platelet adhesion. Finally, the platelet adhesion from the platelet suspensions was reduced after the removal of the gas nuclei. Thus the platelets themselves sense the change in the surface resulting from the removal of the gas nuclei.


Effect of hematocrit variations on coronary hemodynamics and oxygen utilization. Twenty-five closed-chest pentobarbitalized dogs were used for studying coronary flow dynamics and myocardial oxygen utilization following variations of hematocrit (Hct) by isovolumetric exchange of blood with plasma or packed red cells. Coronary blood flow (133Xe washout) and cardiac output varied inversely with Hct. Coronary systemic, and pulmonary flow resistances varied in the same direction with Hct. Blood viscosity played a significant role in determining the flow resistances in these three regions. Analysis of vascular hindrance (vascular resistance/blood viscosity) suggested that coronary vasodilation occurred following Hct changes beyond the range of 20-60%. In systemic and pulmonary circulations, however, there was vasoconstriction following hemodilution. The range of optimum Hct for maximum O2 transport (blood flow X arterial O2 content) was much wider in coronary (20-60% Hct) than in systemic circulation (40-60% Hct). The O2 consumptions in total body and in myocardium were essentially constant over a wide range of Hct (20-60%). The maintenance of total body O2 consumption over the Hct range of 20-40% was attributable to an increase in A-V O2 extraction. The O2 extraction ratio in the coronary circulation was constant over the entire range of Hct studied, suggesting that the myocardial O2 consumption was primarily determined by the coronary O2 transport.


Capillary lengths, anastomoses, and estimated capillary transit times in skeletal muscle. Total capillary length, capillary segment length, and number of anastomoses per capillary were measured in rat gracilis muscle at rest and after 2 min of phasic contraction. Mean values of the foregoing variables at rest (+/-SD) were, respectively, 1,012 micronm +/- 484, 409 micron +/- 274, and 0.83 +/- 1.09. Total capillary lengths are well described by the gamma distribution, number of anastomoses by the negative binomial distribution, and segment length by the Weibull distribution. Contraction has no significant effect on the means or the frequency distributions, indicating that: 1) pressure gradients between adjacent capillaries are small, and 2) intercapillary anastomoses do not improve flow distribution in exercise. Erythrocyte velocities observed in resting muscle (Burton, K. S., and P. C. Johnson. Am J. Physiol. 223: 517-524, 1972) were shown to be adequately characterized by the gamma distribution. From these velocities and the observed distribution of path lengths, we computed an estimated distribution of capillary transit times. Mean transit time was 4.29 s. The median was 2.45 s, and 11% of values exceeded 8 s. The range was 90 ms-43 s. This heterogeneity of transit times should profoundly affect calculations of O2 transport and the shape of indicator dilution curves.


Determinants of isogravimetric capillary pressure in the isolated dog hindlimb. The hindlimb of the dog was rapidly isolated and carefully perfused in an attempt to prevent transcapillary fluid shifts into the interstitium which may occur during normal surgical isolation and perfusion. In the control preparation before weight was allowed to increase, isogravimetric capillary pressure (Pci) averaged 8 mmHg lower than colloid osmotic pressure of the plasma (IIp). As the weight of the leg was increased, Pci increased and IIp - Pci decreased. When weight was increased by 5.8%, IIp - Pci averaged 3 mmHg; with a 9.8% increase in weight, IIp - Pci averaged 1.3 mmHg. The calculated value of compliance of the interstitial space averaged 0.50 ml/mmHg per 100 g of tissue and increased approximately 10-fold as the weight of the leg was increased. Since IIp - Pci has always been reported to be approximately 2 mmHg when the hindleg was isolated with standard surgical techniques, these data suggest that the procedures normally used to isolate and perfuse the hindlimb caused the weight of the limb to increase by 6% or more before Pci was determined. Furthermore, it appears that most of the variation in the reported value of Pci is due to variation in the value of IIp since IIp - Pci has always been reported to be very close to 2 mmHg in the isolated hindlimb.


Effects of systemically infused histamine on transvascular fluid and protein transfer. Histamine (4-64 microgram base/min) infused into the brachial artery clearly promotes edema formation in forelimbs perfused at natural flow. In contrast, intravenously administered histamine, even in blood concentrations exceeding those achieved by local infusion, not only fails to promote edema formation, but rather causes net extravascular fluid reabsorption. In this study, high concentrations of histamine were infused into the left ventricular chamber to bypass the pulmonary circuit. Histamine (400-800 microgram base/min) infused into the left ventricle of the heart for 90 min produced marked hypotension and only very slight increases in forelimb skin lymph flow and lymph protein concentration and failed to produce visible signs of edema. Thus the differential actions of local and intravenous histamine on lymph flow, protein efflux, and fluid fluxes cannot be explained by uptake or destruction of histamine in the lung during intravenous infusions of this agent. It seems more likely that they result from different actions on microvascular pressure, surface area, and/or permeability to plasma proteins. Prior hypotension produced either by acetylcholine, systemically infused histamine, or arterial hemorrhage almost completely prevents the increase in skin lymph flow and lymph protein concentration by histamine infused locally into the brachial artery, even in forelimbs perfused at constant flow.


Elasticity and compliance of canine femoral and jugular vein segments. In this study, the pressure/strain and stress/strain relatioships of 44 jugular and 31 femoral canine vein segments were compared with 17 carotid artery specimens, latex rubber, and a synthetic graft material, expanded polytetrafluoroethylene. A method is described for comparing the elastic properties of vein wall specimens of varying thicknesses such as occur after implantation into the arterial circulation. A flat sheet of opened vessel wall, fexed between retention rings at one end of a saline-filled steel cylinder, was biaxially distended to form a bubble shape. Compliance ratio and stress modulus were computed at 20-mmHg increments from 20 to 200 mmHg. In the "arterial" pressure range, vein was less compliant than artery. Vein also had a higher stress modulus E (dyn/cm2 X 10(6)) +/- SE at a chamber pressure 120 mmHg than artery (E = 11 +/- 0.6), and jugular vein was stiffer (E = 65 +/- 3.6) than femoral vein (E = 41.5 +/- 2.0). Changes in the structural properties of vein grafts measured using this technique are potentially important factors leading to graft failure.


Nonexcised papillary muscle preparation: force and length measurement and control. An electromechanical servocontrol system was developed to analyze mechanical properties of a nonexcised, blood-perfused papillary muscle. A miniature load cell mounted on the moving arm of a pen motor measured muscle force, and a shaft angle sensor built in the motor measured the length. The pen motor was actuated by a servocontrol command signal. A papillary muscle was exposed in the right ventricle of an excised, cross-circulated canine heart. The tendinous end of the papillary muscle was connected to the load cell. The intact root of the muscle was fixed by a metal ring. The preparation was stable over 5 h heating at a regular spontaneous heart rate (95-150/min) at 37 degrees C. The system allowed the muscle to contract in various modes such as isometric, isotonic, auxotonic, afterloaded isotonic, quick released, lengthening, etc. Changes in the contraction mode, preload, and afterload could be achieved at the investigator's disposal simply by turning switches and potentiometers, or by feeding external command signals of desired wave forms.


Noninvasive measurements of digital arterial pressure and compliance in man. A noninvasive method was developed for measuring the digital arterial pressure and the compliance by using a fingertip pneumoplethysmograph and a pneumatic cuff. The compliance (C) of the digital artery was obtained from the peak amplitude of the volume pulse wave (deltaVp-a) under the effect of the cuff pressure (Po-a) by the equation: C = deltavp-a/(Ps - P-o-a) during the dicrotic phase defined in this study. The normal mean value was 11.37 +/- 0.59 X 10(-5) cm3/mmHg. On lowering of the cuff pressure, the moment when the deltaVp value becomes positive is regarded as the systolic pressure (Ps). At the end of the dicrotic phase, the mean amplitude (deltaVss') of the pulse wave during one pulse cycle (SS') and the ratios (deltaVss'/deltaVsd), where deltaVsd is the mean amplitude of the wave during the systolic period (SD), of successive waves after a particular wave fail to increase at the same rate when the cuff pressure decreased below the diastolic pressure. The cuff pressure corresponding to this particular wave is regarded as the diastolic pressure (Pd). The mean value of the mean digital pressure of normotensive subjects was 80.6 +/- 1.2 mmHg.


Dynamics of myocardial oxygen consumption and coronary vascular resistance. Coronary vascular resistance may be regulated in part by substances whose concentrations are determined by or reflect the rate of myocardial oxygen consumption (e.g., adenosine, vessel wall PO2). We tested this hypothesis by comparing the time course of changes in myocardial oxygen consumption and coronary vascular resistance following 20 beat/min changes in heart rate. Main left coronary arteries of in situ dog hearts were perfused with blood at constant flow. Coronary sinus O2 content was monitored continuously with a densitometer and reflected the time course of changes in oxygen consumption and also the effects of vascular transit between tissue and the coronary sinus. These transit effects were estimated from dye transit curves and added to the time course of changes in coronary perfusion pressure which was proportional to coronary vascular resistance at constant flow. Coronary sinus O2 content changes preceded the adjusted time course of vascular resistance. This supports the hypothesis that coronary vascular resistance is regulated in part by factors closely linked to oxidative metabolism.


Effect of anomalous pathway location on rate of canine experimental A-V reentrant tachycardia. The effect of anomalous pathway (AP) location and conduction time on the cycle length (CL) and sustainability of paroxysmal A-V reentrant tachycardia was studied in 15 dogs, using an anomalous pathway simulator (APS). The APS was a programmable digital electronic circuit with ability for unidirectional conduction, ventricular sensing, adjustable delay, and atrial stimulation. Contiguous pairs of ventricular sensing electrodes were placed along the A-V ring in each dog at the following sites: anterior, posterior, and lateral right (AR, PR, and LR) and anterior, posterior, and lateral left (AL, PL, and LL) and septal (S). There were significant differences in the CL of tachycardias among the tested sites (P less than 0.01). The CL of tachycardias from the LL site was significantly longer and from the PR site significantly shorter than that from the other sites (P less than 0.05). These differences in CL of tachycardias in relation to the AP location were explicable in terms of corresponding variation in conduction times of the various components of the tachycardia circuit (e.g., intra-atrial, A-V nodal, intraventricular conduction times). The differences in magnitude of the CL of tachycardias, although significant, were small. It was also found that all sites allowed maintenance of tachycardias up to an AP conduction time of 10 ms. In 27% of experiments, atrial refractoriness prevented sustained tachycardias at pathway delays of 1 ms. The relationship between AP conduction time and CL of tachycardias was exponential.


Effect of vasopressin on the mixing of portal venous blood in awake man. Transumbilical portal venous catheterization was performed in 11 patients for diagnostic selective portography. By use of a multiple-catheter technique, the effects of intravenous infusion of [8-lysine]vasopressin on portal venous mixing of tributary flows was measured by simultaneous blood sampling from the left and right portal branch, taking advantage of the oxygen saturation difference between splenic and superior mesenteric venous blood and also by infusion of 133Xe into one of the portal tributaries. Slight signs of incomplete portal mixing were observed at rest in eight of nine patients. During vasopressin infusion, the heterogeneity of oxygen saturation and xenon activity in the portal branches increased significantly. There was also a significant average shift of splenic venous blood toward the left portal branch with, in some patients, only splenic blood in this branch. Streamlining thus was a dynamic phenomenon related to the reduced and altered portal venous flow pattern. This must be considered during flow measurements, and might also have pathophysiological significance in liver diseases.


Contractile stimuli in collecting lymph vessels. Contractility was investigated in collecting lymph vessels of rat and guinea pig mesentery. Lymphatic diameter and micropressure were simultaneously recorded under normal conditions and during micromanipulation of intralymphatic pressure. Spontaneous activity involved characteristic changes in intralymphatic pressure coincident with opening and closure of upstream and downstream valves. Contractions were irregular but still predictable by noting the trend of intraluminal pressure as it approached a threshold level. Mechanical obstruction upstream of lymph vessels reduced lymph pressure and contraction frequency. Microinjection or withdrawal of fluid caused contraction frequency. Microinjection or withdrawal of fluid caused contraction frequency to rise and fall, respectively. Contraction rate was not affected by the level of general anesthesia. Lymphatic wall tension, as calculated from pressure-radius variables, correlated well with contraction frequency, suggesting a myogenic origin for the contractile mechanism. However, lymphatic smooth muscle may be inherently unstable since some contractility persists despite an absence of pressure stimuli.


Simultaneous accumulation of Evans blue dye and albumin in the canine aortic wall. The simultaneous transport of Evans blue dye (EBD) and 125I-labeled canine albumin (IALB) across normal and injured endothelial surface was measured by determining the intimal accumulation of EBD (ME) by a reflectometric method and accumulation of equimolar concentrations of EBD and IALB, ME was related to MI by ME = 0.092 + 5.04 MI - 0.508 MI2 for injured and ME = 0.002 + 0.435 MI (nmol-cm-2) for normal surfaces. Both ME and MI varied nonlinearly with exposure time for injured and linearly with time for normal surfaces, giving apparent permeability coefficients of 0.92 X 10(-8) cm-sec-1 for EBD and 2.00 X 10(-8) cm-sec-1 for albumin. These results show that the transvascular flux of EBD can be related to that of albumin by empirical equations, which is of practical importance but also implies unique underlying physical laws. Study of these physical laws will provide deeper insight into transvascular macromolecular transport processes.