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Biomedical subjects

E D Verrier

Publications and source records attributed to E D Verrier.

At least 91 records · Page 5Linked to original sources
PubMed1989

Etiology of intestinal damage in gastroschisis. I: Effects of amniotic fluid exposure and bowel constriction in a fetal lamb model.

Gastroschisis is often complicated by damage to the herniated small bowel, resulting in motility and absorption disturbances and occasional intestinal necrosis and atresia. To study the pathophysiology of this process, a model of gastroschisis was developed in fetal lambs. At 80 days' gestation, the anterior abdominal wall was partially excised to create a small peritoneal cavity, and the small bowel was extruded through a Silastic ring to create a defect of uniform size. In one experimental group, a tie was placed around the herniated bowel at the level of the abdominal wall to provide gradual constriction as the fetus grew. In a second group, no tie was placed. Control animals had a simple laparotomy and no abdominal wall defect; some also had a constrictor placed around the base of the bowel. The animals were delivered near term, and the bowel was evaluated histologically and by an in-vitro bowel motility assay. Histologic examination showed normal ganglion cells in all groups and no evidence of ischemic injury. A fibrous peel was seen only in bowel exposed to amniotic fluid, with or without a constrictor. Lymphatic and venous dilation, smooth-muscle thickening, and focal mucosal blunting were seen in bowel subjected to chronic obstruction by a constrictor, regardless of whether it was exposed to amniotic fluid. Both constriction of the bowel and amniotic fluid exposure were associated with a decrease in motility; these two effects were independent and additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1989

Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid.

Fetal wound healing without scar formations, fibrosis, or contracture might be accompanied by major differences in the wound extracellular matrix. The matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. Although hyaluronic acid is a critical molecule for both embryonic development and wound healing, no factor has yet been identified that modulates hyaluronic acid in a consistent manner. We describe here a substance present in fetal sheep serum that stimulates hyaluronic acid synthesis by cultured fibroblasts. This glycoprotein factor appears to be ubiquitous, present in fetal sheep and bovine serum, reaching a peak in each at 40% of the way through gestation. This factor is also present in amniotic fluid. It might control hyaluronic acid deposition. In turn, hyaluronic acid, by creating an extracellular environment permissive for cell motility and proliferation, might be critical for fetal development. We suggest that the same sequence of events underlie the unique properties observed in fetal wound healing.

Animals↗
PubMed1989

Studies in fetal wound healing: II. A fetal environment accelerates fibroblast migration in vitro.

We have used an in vitro model of wound healing using scratches made in a confluent monolayer of fibroblasts. The effects of fetal calf and postnatal calf serum on the migration of fibroblasts were compared. Differences between fetal and calf serum-incubated fibroblasts grown on coverslips were observed within 15 minutes of exposure. Cells in fetal serum began to change both shape and orientation and to move into the trough created by the scratch. The fibroblasts incubated in fetal calf serum completely filled in the trough within 16 hours while those incubated in calf serum did not do so even after 24 hours. We estimate that, at any point, there was a 50% lag time in the migration of the fibroblasts in the presence of postnatal calf serum. This difference in migration and filling was not a function of mitogenesis; the mitogenicity of the two sera were comparable. The results suggest that fibroblast migration in vitro is accelerated by the fetal serum. A similar mechanism may occur in vivo and may underlie the ability of the fetal wound to heal more rapidly.

Animals↗
PubMed1989

Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing.

Wound healing in the fetus proceeds through a series of steps that differ in the fetus and the adult. At each phase of this complex process, there is signaling between the tissue cells and the wound microenvironment, signals that are mediated by and through the extracellular matrix. We postulate that these signals occur earlier in fetal wounds, resulting in more rapid repair. To investigate this, we compared the first 24 hours of wound healing in the rabbit fetus and adult, using antibodies against key extracellular matrix macromolecular components: laminin, fibronectin, and type-specific collagens I, III, IV, and V. Fibronectin was the first matrix component to be deposited, and was visualized as early as four hours after fetal wounding and 12 hours after adult wounding. There was no evidence of new laminin or collagen deposition in either the fetal or adult wounds at any time point examined. The early deposition of fibronectin, a matrix adhesion molecule that provides a scaffolding for epithelial migration, may underlie the rapid reepithelialization observed in fetal wounds.

Animals↗
PubMed1989

Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid.

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Age Factors↗
PubMed1989

A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations.

Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting.

Aged↗
PubMed1989

Neonatal model of heterotopic heart transplantation in pigs.

To investigate the long-term success of heart transplantation in newborn infants who have complex congenital heart disease, we have developed a model of heterotopic heart transplantation in immature pigs. We chose the heterotopic technique because it is simple, does not require cardiopulmonary bypass or heparin, allows for significant size disparity between the recipient and donor hearts, and allows for experimental comparisons between the two hearts. Small newborn piglet hearts are harvested, prepared, and then transplanted into the left chest of larger weanling pigs to augment or substitute for the native left ventricle. Preliminary data from transplants into 49 pigs suggest that the technique is technically possible, the pigs can be immunosuppressed over the long term, and the donor heart can contribute hemodynamically. Experimentally, the model is well designed for the investigation of issues critical for the long-term success of heart transplantation in infants and children, including growth and development, optimal long-term immunosuppression, differences in immunotolerance, and the study of coronary obliterative disease. Clinically, the model has potential applicability in congenital heart anomalies if one native functioning atrium and ventricle are present.

Animals↗
PubMed1988

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart.

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.

Animals↗
PubMed1988

The fate of the 12 mm porcine valved conduit from the right ventricle to the pulmonary artery. A ten-year experience.

The 12 mm Dacron conduit containing a porcine valve is the smallest valved conduit manufactured and is used in the youngest infants with the most diminutive pulmonary arterial system. The outcome of patients with such a conduit is unknown. Between 1975 and 1985 there were 49 hospital survivors after placement of a 12 mm extracardiac valved conduit from the right ventricle to the pulmonary artery. Follow-up is available in 42 patients, aged 1 to 16 months (mean 3.5) and weighing 2.5 to 8.7 kg (mean 3.8). Twenty-eight patients (67%) have undergone subsequent conduit replacement, and 11 (26%) are alive and asymptomatic with a mean follow-up of 56 months. There were three late deaths. The interval between implantation and conduit change was 4.5 to 101 months (mean 44), allowing a weight gain of 2.7 to 23 kg (mean 10.4) before reoperation at age 12 to 117 months (mean 49). Despite elevated right ventricular pressures equaling systemic values, 37% of these patients were clinically asymptomatic. The gradient across the 12 mm valved conduit before explantation ranged from 30 to 173 torr (mean 83) with an almost equal predilection for stenosis at the proximal anastomosis, valve, conduit, distal anastomosis, and main pulmonary artery. The intervening pulmonary artery growth determined the size of the replacement conduit, 14 to 25 mm (mean 16), and was the main factor influencing the results of reoperation. This study demonstrates that the 12 mm porcine valve-containing conduit affords palliation in this difficult subset of patients with the smallest pulmonary arterial tree.

Bioprosthesis↗
PubMed1988

The Mustard procedure in infants (less than 100 days of age). Ten-year follow-up.

Surgical treatment of transposition of the great arteries and intact ventricular septum has changed markedly in the past 10 years. However, long-term follow-up on new approaches is not available. In a unique group of patients, operated on in the first 100 days of life with the Mustard procedure, such follow-up is available, and the results of these true infant repairs represent a benchmark against which subsequent techniques applied to infants should be compared. During the period of 1975 to 1980, 36 infants, less than 100 days of age, who had transposition of the great arteries and intact ventricular septum, underwent Mustard repair at the University of California, San Francisco. Ages ranged from 4 to 98 days (mean 46 days) and weights from 2.3 to 6.6 kg (mean 3.5 kg). There were no early deaths, and late follow-up was available from 8 to 13 years (mean 10 years). The late survival rate was 97% (mean 10 years). There was a 62% rhythm disturbance-free survival rate, 89% reoperation-free survival rate, and 91% pacemaker-free survival rate. Echocardiographic evaluation revealed obstruction of the superior vena cava in eight patients, tricuspid insufficiency in four, right ventricular dysfunction in two, and left ventricular outflow tract obstruction in three. The Mustard procedure, performed in the first 100 days of life, results in a high rate of survival (early 100% and late 97%, at a mean of 10 years) and a low incidence of late complications against which other techniques of infant repair should be compared.

Echocardiography↗
PubMed1987

Effects of isoflurane and halothane on coronary vascular resistance and collateral myocardial blood flow: their capacity to induce coronary steal.

Some coronary vasodilators, paradoxically, may endanger patients with coronary artery disease by causing "coronary steal." To determine the capacity of isoflurane and halothane to cause coronary steal, the authors studied their effects on coronary vascular resistance (CVR), diastolic coronary artery pressure, and collateral myocardial blood flow. Using ameroid constrictors, chronic occlusions of the left anterior descending (LAD) coronary artery were created in ten dogs. Six to eight weeks after implantation, the dogs were anesthetized with fentanyl and pentobarbital, and a stenosis was created on the circumflex (Cx) coronary artery. Isoflurane and halothane were each administered in doses of 0.5 and 1.5 MAC. Diastolic aortic pressure was held constant. Using small catheters in the circumflex and LAD coronary arteries, the authors measured diastolic coronary artery pressures. Collateral myocardial blood flow was measured by the microsphere method. In this model, halothane and isoflurane minimally affect CVR. The maximum change in CVR, which was found during 1.5 MAC isoflurane, was -8% (not significant). Diastolic coronary pressures distal to the Cx stenosis (54.5 +/- 11.5 mmHg) and distal to the LAD occlusion (44.5 +/- 5.2 mmHg) did not change significantly with either isoflurane or halothane. Transmural collateral blood flow distal to the LAD occlusion (0.51 +/- 0.11 cc.g-1.min-1) was unaltered by either drug. There was no evidence of coronary steal. Epicardial ECG S-T segments showed no evidence of ischemia. The finding of minimal direct effects of halothane and isoflurane on CVR, diastolic coronary pressure, and collateral myocardial blood flow suggest that, under the conditions of this study, neither agent, when used as an adjuvant to high-dose narcotic anesthesia, is likely to cause myocardial ischemia by a coronary "steal" mechanism.

Animals↗
PubMed1986

Infant coarctation: a spectrum in clinical presentation and treatment.

Between 1975 and 1985, 125 infants 2 to 365 days old (majority, 30 days old or less) with coarctation of the aorta underwent surgical repair. Forty-seven patients (38%) had severe congestive heart failure (CHF), metabolic acidosis, and poor systemic perfusion. The predominant operative technique was synthetic patch aortoplasty (100 patients); the remaining 25 had an end-to-end anastomosis. There were no operative deaths. Perioperative complications were minimized with the synthetic patch technique (less than 15%). For patients surviving at least 3 months after repair, the arm-leg systolic blood pressure gradient was relieved in 82% (71/87) of the patients having patch aortoplasty versus 65% (15/23) of the patients with end-to-end anastomosis. Although the rate of reoperation between the two groups was similar (patch, 5 [6%]; end-to-end, 3 [13%], two of the reoperations in the patch group were for preexisting hypoplastic transverse aortic arch. Late deaths (20 patients, 16%) were due to other major associated cardiac anomalies. Patch aneurysms have not occurred. Expedient use of synthetic patch aortoplasty has decreased perioperative complications, relieved coarctation gradients for CHF, increased early survival even in the presence of complex or associated cardiac anomalies, and has an acceptable rate of recurrent coarctation (6 to 13%).

Aortic Coarctation↗
PubMed1986

Coronary vasodilation shifts the diastolic pressure-dimension curve of the left ventricle.

The volume of blood in the left ventricular wall increases as coronary perfusion pressure or coronary blood flow increase, but it is unclear whether such an increase in volume can acutely alter the diastolic pressure-dimension relationship of the intact, working left ventricle. In 19 dogs, we measured left ventricular pressure with a catheter tip transducer and dimensions with an epicardial echo transducer and, during each experiment, compared the diastolic pressure-dimension relationship during two states of coronary blood flow: control and maximal vasodilation (induced by intravenous chromonar). Diastolic pressure-dimension relationships for diastolic pressures from 0 to 25 mmHg were obtained during transfusion with blood in 11 dogs with the pericardium open and in eight dogs with the pericardium closed. Left ventricular epicardial diameter did not change during maximal coronary blood flow compared with control, but endocardial diameter was less, wall thickness was greater, and the diastolic pressure-dimension relation was shifted to the left. The average magnitude of the increase in diastolic pressure at comparable diastolic dimensions was small when the pericardium was open (2.6 mmHg) and larger when the pericardium was closed (4.1 mmHg). The mechanism of this shift appears to be an alteration of the ratio of diastolic chamber volume to wall volume. Interaction of diastolic pressures between the right and left ventricles may contribute to the larger increase in diastolic pressure with the pericardium closed.

Animals↗
PubMed1986

Aspirin anticoagulation in children with mechanical aortic valves.

The optimal method of anticoagulation in children with mechanical heart valves is controversial. Between 1975 and 1986, aspirin or aspirin with dipyridamole has been used for anticoagulation in children receiving a mechanical aortic valve at the University of California, San Francisco. Fifty-one patients (ages 1 to 23 years, mean 12.9 years) were treated with aspirin (n = 45) or aspirin with dipyridamole (n = 6) and observed a mean of 36.5 months (range 3 to 100 months). There were four late deaths: two from endocarditis and two from other medical problems, but none related to thrombosis or embolus. Follow-up was accomplished by direct contact with the patient, parent, or referring physician. Two patients (3.9%) were lost to late follow-up. One minor neurologic event occurred perioperatively and resolved spontaneously. There were no postoperative thromboembolic events. Eleven asymptomatic children were recently studied by magnetic resonance imaging or computed axial tomography of the brain and had no evidence of prior silent cerebral thromboembolic defects. There were four patients (5.9%) who had minor hemorrhagic complications: Three patients had nosebleeds and one patient had an upper gastrointestinal hemorrhage. Five patients were changed to warfarin anticoagulation: the patient with upper gastrointestinal hemorrhage and four older patients because of physician preference, all after uncomplicated aspirin therapy. There were no mechanical valve failures, although one patient required reoperation 9 months later for perivalvular leak. All children have remained in normal sinus or paced rhythm during follow-up. These results show that children with mechanical aortic valves in normal sinus rhythm can be safely treated with aspirin (or aspirin with dipyridamole) with little risk of thromboembolic events, valve thrombosis, or valve failure. Hemorrhagic complications resulting from aspirin are minor and easily treated.

Adolescent↗
PubMed1984

Increased number of myocardial blood flow measurements with radionuclide-labeled microspheres.

We evaluated the use of a least-squares radionuclide separation technique to allow an increased number of myocardial blood flow measurements with radionuclide-labeled microspheres in dogs. Two sets of labeled microspheres were studied: a set of eight labeled with 125I, 153Gd, 57Co, 51Cr, 113Sn, 85Sr, 95Nb, and 46Sc; and a set of nine in which 125I and 46Sc were replaced with 114In, 54Mn, and 65Zn. For each microsphere label the nuclide activities determined by least-squares separation compared favorably with those actually added to in vitro samples containing a fixed amount of the other nuclides in the set. For the set of eight radionuclide-labeled microspheres, myocardial flow measurements made with the least-squares separation technique and the reference sample method were usually within 15% and almost all within 20% of direct measurements of coronary venous outflow in a right heart bypass preparation. Serial left atrial injections of 15-micron microspheres totaling 48 X 10(6) caused no significant changes in systemic hemodynamics, regional myocardial flows, or coronary pressure-flow relations, whether the coronary bed was autorelating or vasodilated with chromonar. We conclude that at least nine myocardial blood flow measurements can be made in dogs with acceptable accuracy and without evidence of dysfunction due to embolization of the coronary vascular bed. With appropriate validation, this method should be applicable to other organs and animal models as well.

Animals↗
PubMed1984

Intestinal infarction complicating phenobarbital overdose.

Nonocclusive intestinal infarction developed in a 29-year-old man after phenobarbital overdose. He was found 72 hours after the overdose, at which time examination of the abdomen disclosed no abnormalities and he was not hypotensive. During the next ten hours, abdominal distention, ileus, and gas within the intestinal wall and portal venous system developed. Laparotomy disclosed ischemic intestinal infarction of the right colon and distal ileum with no evidence of thrombosis of the mesenteric vessels. The patient recovered fully after ileostomy with subsequent reanastomosis. To our knowledge, ischemic intestinal infarction after drug overdose has not been reported previously.

Adult↗
PubMed1983

Volume loading improves low cardiac output in experimental right ventricular infarction.

To evaluate the effect of volume loading in the low output state associated with right ventricular infarction, isolated right ventricular infarction was produced in seven dogs with the pericardium intact. Volume loading and pericardiotomy were then sequentially performed. After the production of right ventricular infarction, right ventricular systolic pressure decreased by 25%, aortic pressure by 36% and cardiac output by 32%. Right ventricular ejection fraction decreased by 57%, but left ventricular ejection fraction did not change significantly. Left ventricular transmural pressure and diastolic size decreased, and right ventricular diastolic size increased. Intrapericardial pressure increased and equalization of diastolic pressures was noted. Volume loading resulted in increased right ventricular systolic pressure and stroke work, increased aortic pressure and cardiac output and increased transmural pressure and diastolic size in both ventricles. Pericardiotomy resulted in further increases in right and left ventricular filling, stroke work and cardiac output, as well as resolution of equalized diastolic pressures. These results indicate that cardiac output in experimental right ventricular infarction increases with volume loading, which enhances left ventricular preload by augmenting right ventricular output. Elevated intrapericardial pressure affects filling of both ventricles and may play a role in the pathophysiology of low cardiac output in right ventricular infarction.

Animals↗