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Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 145 records · Page 8Linked to original sources

Effects of aspirin and acetaminophen in pregnancy and in the newborn.

Inhibitors of prostaglandin synthesis are increasingly recommended for delaying premature delivery. However, such inhibitors--eg, aspirin, indomethacin, or naproxen--may interfere with uterine contractility, with maternal, fetal, and neonatal platelet function, and especially with fetal circulation and postnatal adaptation. The instillation of aspirin (50 to 90 mg/kg of fetal body weight) into the rumina of fetal lambs resulted in significant increase of pulmonary arterial pressure, which was directly related to constriction of the ductus arteriosus. Such pressure elevation may act as a stimulus to increased muscular development in the small vessels of the lung, which, in turn, could interfere with the rapid reduction in pulmonary vascular resistance normally occurring after birth. The effects of acetaminophen in pregnancy and in the newborn have not been studied extensively; when ingested in usual therapeutic doses, the available data have shown no adverse effects.

Abnormalities, Drug-Induced↗

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↗

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↗

Role of renin-angiotensin system in response to hemorrhage in fetal sheep.

During fetal life, the autonomic nervous system is not fully mature, and it is likely that hormonal mechanisms play an important role in controlling cardiovascular function. In chronically instrumented fetal sheep, hemorrhage increased plasma renin activity and plasma angiotensin concentration significantly from 6.7 +/- 2.5 to 15.2 +/- 3.1 ng.ml-1.h-1 and from 74 +/- 19 to 182 +/- 43 pg/ml, respectively. Both mean arterial and venous blood pressures decreased initially from 45 to 35 Torr and from 3.5 to 2.5 Torr, respectively; then both returned to control values. Fetal heart rate decreased initially from 174 beats/min and then increased to 186 beats/min. To determine whether angiotensin had a role in mediating these responses to hemorrhage, we hemorrhaged a second group of fetuses before and during infusion of saralasin, a competitive antagonist of angiotensin. Hemorrhage during infusion of saralasin decreased heart rat from 170 to 145 beats/min and further decreased mean arterial pressure to 30 Torr. Cardiac output decreased from 436 +/- 25 to 368 +/- 30 ml.min-1.kg-1, and umbilical-placental blood flow decreased from 205 +/- 20 to 145 +/- 10 ml.min-1.kg-1. We conclude that the renin-angiotensin system plays a major role in the response to hemorrhage in fetal sheep.

Angiotensin II↗

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↗

Effects of angiotensin II on the blood flow and its distribution in fetal lambs.

We studied the effects of intravenous infusion of angiotensin II on the circulation of the fetus in lambs in utero through chronically maintained intravascular catheters. Angiotensin II infused in doses of 29-280 ng/min per kg fetal weight resulted in an increase in plasma angiotensin II from a control value of 87 +/- 17 to 341 +/- 129 (mean +/- SE) pg/ml; these levels are similar to those observed following hemorrhage in fetal lambs. Fetal mean arterial blood pressure increased from 46 +/- 2.0 to 56 +/- 2.7 torr and fetal heart rate increased from 172 +/- 6 to 189 +/- 6 beats/min, an effect which was not altered by beta-adrenergic or cholinergic blockade. Fetal cardiac output and its distribution were measured before and during infusion of angiotensin II by the radionuclide-labeled microsphere technique. Combined ventricular output increased significantly from 526 +/- 32 to 616 +/- 24 ml/min per kg fetal body weight. Angiotensin constricted the umbilical-placental circulation as well as the gastrointestinal, renal, and thyroidal vascular beds. Angiotensin increased blood flow to the myocardium and markedly increased blood flow to the pulmonary circulation. These studies indicate that angiotensin II, at the plasma levels achieved with moderate hemorrhage, has marked influences on the circulation. The renin-angiotensin system may be important in the fetal response to stress.

Adrenergic beta-Antagonists↗

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↗

A preparation for studying liver blood flow, oxygen consumption, and metabolism in the fetal lamb in utero.

We present a method for chronic catheterization of the hepatic veins of fetal lambs in utero. A detailed description of hepatic venous anatomy, essential to the technique, is also presented. Right, left, or both hepatic veins were catheterized successfully in 23 of 28 animals. We assessed catheter position accurately during surgery by comparing oxygen saturations in the hepatic vein, descending aorta, umbilical vein, and inferior vena cava. Right hepatic venous saturation usually closely resembles that in the descending aorta, whereas left hepatic venous saturation lies between aortic and umbilical venous saturations. Samples obtained through these catheters are representative of hepatic venous blood and are not contaminated by reflux from the inferior vena cava. These small catheters are unlikely to alter the distribution of blood within the liver or streamlining of blood within the thoracic inferior vena cava. When this technique is coupled with catheterization of the descending aorta, umbilical vein, and portal vein, the preparation allows quantitation of blood flow, oxygen consumption, and metabolism in the liver of the unanaesthetized fetal sheep in utero.

Animals↗

The effects of nonsteroidal antiinflammatory compounds on fetal circulation and pulmonary function.

Nonsteroidal antiinflammatory compounds that act by inhibiting synthesis of prostaglandins from arachidonic acid have been shown to have various and sometimes profound effects on fetal and neonatal circulation. Agents such as acetylsalicylic acid, indomethacin, and naproxen pass readily across the placenta and have been shown to cause severe constriction and, in some cases, closure of the ductus arteriosus, resulting in an increase in pulmonary blood pressure and a significant pressure gradient between the pulmonary artery and the aorta of the fetus. Inhibitors of prostaglandin synthesis produce only a mild increase in systemic vascular resistance under normal conditions, but have been observed to potentiate vasoconstriction under conditions of hypoxia. Umbilical-placental and myocardial blood flow was increased by these agents. Although single doses of these agents do not appear to affect fetal pulmonary vessels, prolonged pulmonary arterial hypertension resulting from chronic administration may stimulate an increased development of medial smooth muscle in fetal precapillary vessels, resulting in persistent pulmonary hypertension in the newborn. Inhibitors of prostaglandin synthesis have also been shown to produce a marked increase in fetal respiration, resulting in an increased oxygen requirement.

Animals↗

Increased heart rate response to parasympathetic and beta adrenergic blockade in growth-retarded fetal lambs.

To determine the influence of the autonomic nervous system on the circulation of normal and growth-retarded fetal lambs we measured the responses of heart rate and arterial blood pressure to parasympathetic (atropine 0.2 mg/kg) and beta-adrenergic (propranolol 1.0 mg/kg) blockade in the last quarter of gestation. The heart rate response to parasympathetic blockade increased with gestational age in both normal and growth-retarded fetuses but in the growth-retarded fetuses there was a significantly greater response to parasympathetic blockade than in control fetuses from 121 days' gestation to term. The heart rate response to beta-adrenergic blockade did not change with gestational age in normal fetuses. From 131 days' gestation to term the heart rate response to beta-adrenergic blockade in growth-retarded fetuses was significantly higher than in normal fetuses. The systemic arterial blood pressure responses to parasympathetic or beta-adrenergic blockade were similar in growth-retarded and normal fetuses. These results indicate an increased parasympathetic and beta-adrenergic influence on the heart of fetuses whose growth has been retarded. It may also suggest a more generalized increase in parasympathetic and sympathetic tone affecting other organs and systems in the growth-retarded fetal lambs.

Animals↗