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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 109 records · Page 6Linked to original sources

Cardiovascular responsiveness of the pig fetus to autonomic blockade.

We studied the development of responsiveness to pharmacological blockade of parasympathetic, alpha-adrenergic and beta-adrenergic control of the circulation of the pig fetus during the last 30 days of gestation (term is 114 days). Heart rate increased following administration of atropine, the increase in fetuses aged 85-90 days gestation being significantly smaller then at term. Infusion of phentolamine decreased fetal blood pressure, the fall in pressure seen in younger fetuses being less than that observed in fetuses near term. However, when expressed in relation to control pressures, the percentage change was the same at all ages. Propranolol slowed the heart rate of all fetuses with no significant differences between stages of gestation. We conclude that vagal control over the circulation continues to increase during the last month of gestation and that the substantial sympathetic activity seen at the earlier ages studied appeared to show no further development prior to term.

Animals↗

Effect of gestational age on pulmonary metabolism of prostaglandin E1 & E2.

The fetus and prematurely delivered newborn lamb have high concentrations of circulating PGE2 that may play a hormonal role, particularly in maintaining the patency of the ductus arteriosus. We studied the ability of the isolated, perfused lung from immature (100 +/- 2 days gestation, +/- SEM n = 8) and near term (142 +/- 1 days, n = 10; term is 150 days) lamb fetuses to metabolize PGE2 as a function of PGE2 concentration in the perfusate. After an intra-arterial infusion of 3H-PGE2 and 14C-inulin (to act as a marker of extracellular space), the bulk of the 14C-inulin was rapidly cleared through the isolated lung and the majority of the 3H activity appeared after the 14C activity had fallen to negligible values. The 3H activity that was retained longer in the lung was primarily associated with the 15-keto prostaglandin E2 and 15-keto-13,14 dihydro prostaglandin E2 metabolites. Lungs from immature fetal lambs metabolized 25% less PGE2 than did lungs from animals near term. This is consistent with our prior observation that premature lambs have decreased plasma clearance rates (in vivo) and elevated circulating concentrations of PGE2 when compared with term newborn lambs.

Alprostadil↗

The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension.

We studied the separate and combined effects of hyperventilation and administration of dopamine and tolazoline in five infants with pulmonary hypertension managed with indwelling pulmonary artery catheters. In five infants the right-to-left shunt reversed during ventilator-induced respiratory alkalosis (pH greater than 7.6). Response to drugs was variable and unpredictable. One infant could be oxygenated at normal pH during combined dopamine and tolazoline infusion. Other infants showed no response to drugs, or became worse during infusion. The ratio of pulmonary artery to systemic artery pressure averaged 1.14 with standard therapy, but decreased to 0.98 following respiratory alkalosis alone, to 0.87 following drug infusions, and to 0.70 following the combination of alkalosis and drug infusion. These changes were significant by analysis of variance at P less than 0.02, P less 0.001, and P less than 0.001, respectively. Systemic oxygenation was satisfactory in all cases when the pulmonary to systemic pressure ratio was less than 1.0.

Alkalosis, Respiratory↗

Cardiovascular effects of acute hemorrhage in fetal lambs.

The effects of acute hemorrhage were studied in two groups each with six fetal lambs (100-116 amd 128-147 days gestation) 3-4 days after we implanted catheters. Fetal blood pressures, heart rate, arterial blood gases and pH, and combined ventricular output and its distribution (radionuclide-labeled microsphere technique) were measured before and 5 min after removal of 15% of fetal-placental blood volume measured by 125I-albumin dilution. Because there were no differences in responses in the two age groups, the data were pooled. Fetal arterial mean pressure fell significantly (50.7 +/- 2.5 to 45.5 +/- 2.6 mmHg) as did heart rate (186 +/- 6 to 151 +/- 13 beats/min) and arterial blood pH (7.39 +/- 0.02 to 7.30 +/- 0.02); arterial blood carbon dioxide tension rose (39.7 +/- 29 to 44.1 +/- 4.4). Combined ventricular output fell from 610 +/- 58 to 448 +/- 45 ml . kg-1 . min-1 (P < 0.05). Blood flow to the umbilical-placental circulation, as well as to the fetal body, fell significantly. Blood flow to the kidneys, gastrointestinal tracts, and lungs also fell, but flow to other organs was maintained. Blood volume reduction in the fetus markedly influences blood gas exchange, because it results in a reduction of umbilical-placental blood flow associated with the fall in arterial pressure.

Acid-Base Equilibrium↗

Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs.

We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.

Animals↗

Pulmonary vascular disease with congenital heart lesions: pathologic features and causes.

Pulmonary vascular disease, a serious complication of many congenital heart lesions, has three major components: increased muscularity of small pulmonary arteries; intimal hyperplasia, scarring and thrombosis; and reduced numbers of intraacinar arteries. The muscularity is due to increased stress on the vessel wall, and is reversible. The intimal changes may be due to endothelial damage, causing an imbalance between prostacyclin and thromboxane A2 production and leading to local platelet aggregation. This, in turn, may stimulate migration and division of myointimal cells, which thicken the intima and lead to scarring and thrombosis. Extensive intimal changes are probably irreversible, but the possibility of preventing them by use of agents that inhibit platelet aggregation needs to be considered. The mechanism of a decrease in numbers of intraacinar arteries is unexplained. The potential for growth of new vessels after corrective surgery of the cardiac defect is an important factor in restoring pulmonary vascular resistance to normal. Available evidence suggests that this growth potential is reduced after 2 years of age and argues for early surgical relief of pulmonary vascular stresses.

Animals↗

Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease.

The case reports of 492 infants with critical congenital cardiac disease treated with prostaglandin E1 (PGE1) were reviewed to determine the nature and incidence of intercurrent medical events. Forty-three percent of the infants had at least one such event, but only half of these were related to PGE1 and the majority required only minor changes in management. Cardiovascular events were the most common (18% incidence), with cutaneous vasodilation and edema occurring more frequently during intraaortic infusion than during i.v. infusion. Central nervous system events were reported in 16% of the patients. Respiratory depression was reported in 12%, and was particularly common in infants weighing less than 2.0 kg at birth (42%). Hematologic, infectious and renal events appeared for the most part to be unrelated to PGE1. The overall mortality (excluding 19 patients with hypoplastic left-heart syndrome) was 31%; the mortality for the patients with critical coarctation or interruption of the aortic arch was nearly twice that for the cyanotic infants (50% vs 27%). No death was attributed to PGE1 administration. During infusion of PGE1, arterial blood pressure and respiratory activity should be monitored carefully and appropriate supportive steps taken if hypotension or respiratory depression occurs. The development of fever or jitteriness may require reduction of the infusion rate and, in view of the possible increased incidence of infections, the prophylactic use of antibiotics is recommended.

Bacterial Infections↗

Myocardial consumption of oxygen and carbohydrates in newborn sheep.

We measured blood flow to the myocardium of the left ventricular free wall, and blood glucose, lactate, pyruvate, and oxygen concentrations simultaneously in the aorta and coronary sinus 13 times in seven previously instrumented newborn sheep, 4 to 25 days after birth. We calculated arteriovenous difference and consumption of oxygen, glucose, lactate, and pyruvate by the newborn myocardium. Results were compared with recently obtained measurements in the myocardium of fetal and adult sheep (6). Myocardial consumption of oxygen in the newborn (577 +/- 38 microM.min-1.100 g LV-1) was higher than in either the fetuses or the adults. This was associated with a greater myocardial blood flow (201 +/- 21 mm.min-1.100 g LV-1) in the newborns. However, the increased myocardial oxygen consumption in the newborns was commensurate with their increased cardiac work as compared with both the fetuses and adults. Although there is an abrupt postnatal increase in arterial glucose concentration, there was no significant difference in either the myocardial consumption of glucose or the contribution of glucose to the total myocardial energy supply among fetal, newborn or adult sheep. Postnatal decreases in myocardial consumption of lactate and pyruvate are not compensated for by an increase in glucose consumption. In newborn sheep, carbohydrates including glucose, lactate, and pyruvate supply the substrate for no more than approximately one-fourth of the total myocardial energy demands (carbohydrate/oxygen quotient was 0.26).

Animals↗

Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs.

We used pregnant sheep and their fetuses as well as newborn lambs (with and without severe respiratory distress due to prematurity) to study the differences in plasma clearance rate, production rate, and circulating concentrations of immunoreactive PGE2. Fetal PGE2 concentrations were significantly higher than simultaneous maternal concentrations. After delivery by cesarean section, all newborn animals were paralyzed and mechanically ventilated. The PGE2 concentrations fell in those lambs that required only minimal ventilatory support (FIO2 < 0.25) and were similar to maternal concentrations by two to three hours. Newborn lambs that developed severe respiratory distress (FIO2 < 0.55) continued to have concentrations that were even greater than fetal concentrations. The elevated PGE2 concentrations in severely distressed lambs were due not only to a decreased plasma clearance rate but also to an increased production rate of PGE2. Since PGE2 appears to maintain the patency of the ductus arteriosus in the fetus and preterm neonate, we examined the patency of the ductus arteriosus in 3-hour-old newborn lambs by radioactive microsphere injections. The ductus was more widely patent in lambs with higher concentrations of PGE2. The increased circulating concentrations of PGE2 in newborn lambs with severe respiratory distress may contribute to the pathogenesis of patent ductus arteriosus by exerting an additional vasodilatory effect on the vessel.

Animals↗