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Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 163 records · Page 9Linked to original sources
PubMed1980

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↗
PubMed1980

Age-dependent sensitivity of the lamb ductus arteriosus to indomethacin and prostaglandins.

Endogenous prostaglandins inhibit the ability of the ductus arteriosus to contract in response to oxygen. We studied the effects of endogenous prostaglandins and indomethacin (an inhibitor of endogenous prostaglandin production) on isometric contraction of isolated rings of lamb ductus arteriosus from animals of different gestational ages (98 to 103 days and 136 to 147 days; term is 150 days). Rings from animals at about 100 days' gestation have a significantly larger indomethacin-induced contraction than rings from animals near term. The lamb ductus arteriosus forms two prostaglandins that relax the vessel: postaglandin E2 and prostacyclin. PGI2 was three orders of magnitude less potent than PGE2. Rings from the younger animals were significantly more sensitive to the relaxing action of PGE2 and PGI2 than were rings from animals near term. This increased sensitivity of immature animals to endogenous prostaglandins is consistent with the more potent effect of indomethacin on rings from immature animals. These observations are also consistent with the findings that preterm infants have an increased incidence of patent ductus arteriosus and that indomethacin can constrict the ductus arteriosus in preterm infants.

Animals↗
PubMed1980

Arginine vasopressin and prolactin after hemorrhage in the fetal lamb.

Chronically prepared fetal lambs had basal plasma arginine vasopressin (AVP) levels of 1.6 +/- 0.23 pg/ml throughout the final third of gestation. Fetal AVP levels measured by radioimmunoassay were increased significantly to 5.8 +/- 0.92, 9.95 +/- 0.95, and 10.0 +/- 5 pg/ml in association with surgical stress, acute exteriorization, and acidosis or hypoxia, respectively. At 59-65 days gestation three lamb fetuses had a 50-fold increase in plasma AVP levels after acute exteriorization and hemorrhage indicating that the 0.4 gestation lamb fetus is capable of secreting pituitary AVP stores after intravascular volume change, temperature stress, and tactile stimulation. In six chronically catheterized third trimester fetuses, a 10-min, 20% hemorrhage caused a significant fall in fetal blood pressure, heart rate, and hematocrit. Plasma AVP increased significantly to 24.3 +/- 5.8 ng/ml without change in arterial blood gases or pH. Basal plasma prolactin concentration of 9.0 +/- 2.0 ng/ml was unchanged after hemorrhage in five fetuses.

Animals↗
PubMed1980

Myocardial oxygen and carbohydrate consumption in fetal lambs in utero and in adult sheep.

We measured myocardial oxygen, glucose, lactate, and pyruvate consumption in chronically instrumented fetal and adult sheep. Although ascending aortic blood concentration of oxygen was significantly lower in fetuses, myocardial consumption of oxygen was similar in the two groups. This was accomplished by a significantly greater myocardial blood flow in the fetuses. Although ascending aortic blood glucose concentration was significantly lower in fetuses, myocardial consumption of glucose was significantly greater in fetuses. Complete oxidative combustion of all glucose consumed by the fetal heart would supply only one-third of myocardial energy demands, as measured by oxygen consumption. Ascending aortic blood concentration of lactate was similar in fetuses and adults, but myocardial consumption of lactate was significantly greater in fetuses. Complete oxidative combustion of all lactate consumed by fetal hearts would supply almost 60% of myocardial energy demands. Small, but significant, amounts of pyruvate are consumed by both fetuses and adults. Our data indicate that fetal lamb myocardium requires substrates other than glucose alone. The large amount of lactate consumed indicates that there is oxidative metabolism in addition to glycolysis and that lactate is of equal, or perhaps greater, importance as a myocardial energy substrate.

Animals↗
PubMed1980

Heart rate response of fetal and adult sheep to hemorrhage stress.

The responses of heart rate and blood pressure to hemorrhage of 15% of estimated blood volume were studied in 24 chronically instrumented fetal lambs of gestational ages 81-144 days (0.55-0.98 gestation) and 6 conscious adult nonpregnant ewes. A transient tachycardia of 25 +/- 3 beats/min (+ 15 +/- 2%) was noted in the fetuses after removal of about 5% blood volume and reduction of mean arterial pressure of 2 +/- 1 mmHg (8 +/- 2%). With 15% reduction of blood volume fetal mean arterial pressure fell 12 +/- 1 mmHg (27 +/- 2%), venous pressure fell from 3.5 +/- 0.5 to 2.0 +/- 0.5 mmHg, and heart rate dropped by 39 +/- 8 beats/min (22 +/- 4%). The fetal bradycardia during the hemorrhage period was reversed by atropine administration. In adult ewes, mean arterial pressure decreased 12 +/- 3 mmHg, venous pressure was unchanged but heart rate increased by 25 +/- 6 beats/min (29 +/- 8%). These studies indicate the presence of a functional baroreflex by 81 days (0.55 gestation).

Animals↗
PubMed1980

High pulmonary vascular resistance after birth: I. Pathophysiologic considerations and etiologic classification.

The clinical syndrome known as persistent fetal circulation, or persistent pulmonary hypertension of the newborn, is characterized by maintenance of a high pulmonary vascular resistance after birth. The small pulmonary arteries of the fetus have a thick muscular medial layer; they are very reactive, being actively constricted by the low PO2 levels normally present during fetal life. The pulmonary vascular smooth muscle layer is hypertrophied in conditions that result in chronic fetal hypoxia, or a maintained increase in pulmonary arterial pressure. Normally, pulmonary vasodilation occurs rapidly after birth, partly related to physical expansion with gas, but mainly due to the increased PO2 associated with ventilation with air. Based on these developmental considerations, the factors responsible for an increased pulmonary vascular resistance after birth may be classified in three main groups: (A) Acute vasoconstriction due to postnatal hypoxia and aggravated by acidemia; (B) Prenatal increase in pulmonary vascular smooth muscle development; and (C) Decreased cross sectional area of the pulmonary vascular bed due to inadequate numbers of vessels. The various mechanisms that may promote these responses are presented.

Animals↗
PubMed1980

Hemodynamic effects of pulmonary arterial infusion of vasodilators in newborn lambs.

Pulmonary arterial infusion of prostaglandin E2 (mean dose, 1 microgram/kg/min) in term neonatal lambs ventilated with room air resulted in a slight fall in pulmonary arterial pressure (P less than 0.05). Infusion during ventilation with low oxygen mixtures resulted in a parallel fall in pulmonary and arterial pressures and resistances. Intrapulmonary infusion of acetylcholine (mean dose, 3.9 microgram/kg/min) in lambs during ventilation with room air caused a slight fall in mean systemic arterial pressure and systemic vascular resistance. When repeated with low oxygen ventilation, infusion of acetylcholine caused a parallel fall in both pulmonary and systemic arterial pressures and resistances. Infusion of tolazoline at a mean dose of 0.21 mg/kg/min did not change pulmonary or systemic arterial pressures or resistances when the lambs were ventilated with room air or with hypoxic gas mixtures although individual animals experienced marked falls in systemic arterial pressure. Pulmonary arterial infusion of each of the three vasodilators during hypoxic ventilation resulted in potentially adverse hemodynamic effects. This occurred despite prior ductal ligation, implying that doses effective for pulmonary vasodilation may exceed doses without systemic effects particularly in the acute hypoxic state.

Acetylcholine↗
PubMed1980

Antagonism of morphine by naloxone in pregnant ewes and fetal lambs.

We wanted to determine if naloxone antagonizes the direct effects of morphine transferred from the mother to her fetus and if this antagonism resembles fetal narcotic withdrawal. After continuous infusions of morphine into pregnant ewes, injections of naloxone into their fetuses produced increases in fetal arterial blood presure; decreases in fetal heart rate, arterial blood pH, and PO2; and defecation of meconium. There were no maternal responses. Injections of naloxone into the mothers produced the same fetal responses and narcotic withdrawal responses in the mothers. Naloxone, therefore, antagonized the direct effects of morphine in the fetus, and this antagonism produced responses resembling narcotic withdrawal.

Animals↗
PubMed1980

Effects of haemorrhage on myocardial consumption of oxygen and carbohydrate in fetal sheep in utero.

A previous study has demonstrated that fetal myocardial blood flow decreased during haemorrhage. To assess the effects of a decrease in myocardial blood flow on fetal myocardial oxygenation and metabolism, we measured fetal myocardial consumption of oxygen, glucose, lactate, and pyruvate, at rest and during haemorrhage in fetal sheep in utero. During haemorrhage blood flow to the left ventricular free wall decreased. There were no significant changes in blood oxygen content in the ascending aorta or in arteriovenous oxygen difference across the left ventricular myocardium. There was a decrease in consumption of oxygen by left ventricular free wall. There were no significant changes in blood glucose concentration in the ascending aorta or in the arteriovenous difference of glucose, but glucose consumption by the left ventricular free wall decreased. During haemorrhage blood lactate concentration in the ascending aorta and the arteriovenous difference of lactate increased. Because the decrease in blood flow to the left ventricular free wall was proportional to the increase in arteriovenous difference of lactate, myocardial lactate consumption was unchanged. There were no significant changes in pyruvate flux during haemorrhage. Because both myocardial oxygen consumption and demand decrease during haemorrhage, whereas lactate consumption and inner: outer myocardial blood flow ratio were unchanged, this study shows that fetal myocardial blood flow and oxygen consumption decrease during haemorrhage as a reflection of decreased cardiac work.

Animals↗
PubMed1979

Developmental response to indomethacin: a comparison of isometric tension with PGE2 formation in the lamb ductus arteriosus.

We studied the effects of oxygen and indomethacin on the isometric contractile response and the production of PGE2 in isolated rings of lamb ductus arteriosus from animals of different gestational ages (100 to 144 days; term is 150 days). Rings of ductus arteriosus from animals less than 110 days released significantly less PGE2 than did rings from animals greater than 120 days. The indomethacin-induced increase in muscle tension in relation to the decrease in endogenous PGE2 production in preparations from animals less than 110 days gestation was greater than in animals older than 120 days. These findings do not support the hypothesis that immature animals have a larger indomethacin-induced contraction due to an increased production of PGE2 earlier in gestation. They are, however, consistent with a decreased sensitivity to PGE2 in the more mature animals; they also support the hypothesis that the decreased effectiveness of indomethacin on the ductus arteriosus from later gestation animals reflects primarily a decrease in the sensitivity of the vessel to PGE2 during development.

Animals↗
PubMed1979

Oxygen delivery in lambs: cardiovascular and hematologic development.

After birth a decrease in hemoglobin concentration occurs while high metabolic demands are imposed on the infant by the extrauterine environment. Using the resting lamb as a model, we studied the mechanisms that are called into play during this period to maintain oxygen delivery. Measurements were made of oxygen consumption, arterial and mixed venous blood oxygen contents, cardiac output, hemoglobin concentration, percent fetal hemoglobin, 2,3-diphosphoglycerate, and hemoglobin oxygen affinity during the first two postnatal months. There was a rapid decrease in hemoglobin concentration after birth and concomitant decrease in hemoglobin oxygen affinity, changes similar to those described in humans. Cardiac output and oxygen consumption were both very high immediately after birth and declined in parallel, so that arteriovenous oxygen content difference was constant. Thus at rest cardiac output varies as a result of the changing need for oxygen. This relationship is independent of hemoglobin concentration or oxygen affinity within the normal range. If, however, oxygen demands were increased, oxygen delivery might be compromised by a limited ability to increase oxygen extraction during the immediate newborn period or when hemoglobin concentration is lowest.

Aging↗
PubMed1979

Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs.

In 16 chronically prepared fetal lambs we compared the systemic distribution of ductus venosus blood flow with that of abdominal inferior vena caval blood by simultaneously injecting microspheres labeled with different radionuclides into an umbilical vein and into the abdominal inferior vena cava. A significantly greater proportion of ductus venosus blood flow than of abdominal inferior vena caval blood flow supplied the brain, heart, and upper body; this resulted from streaming of ductus venosus blood flow within the thoracic inferior vena cava with preferential direction of that blood flow through the foramen ovale. Blood flows to upper and lower body structures and placenta calculated from umbilical venous microsphere injections and reference arterial blood samples did not differ from those computed fromabdominal inferior vena caval injections and reference samples. Thus, despite streamline blood flow within the fetal thoracic inferior vena cava, organ blood flows can be accurately measured with either an umbilical venous or an abdominal inferior vena caval injection of microspheres when either is combined with the appropriate reference arterial blood samples.

Animals↗
PubMed1979

Dilatation of the ductus arteriosus by prostaglandin E1 in aortic arch abnormalities.

Infants with aortic arch interruption of juxtaductal coarctation of the aorta may depend on patency of the ductus arteriosus to provide adequate lower body perfusion. In many such infants the ductus arteriosus constricts after birth, resulting in severe heart failure, poor systemic perfusion and acidemia. We infused prostaglandin E1 (PGE1) at a rate of 0.05--0.1 microgram/kg/min into seven infants with aortic arch interruption and eight infants with coarctation. In one infant in each group the ductus arteriosus was already closed and did not reopen. In one infant with coarctation an adequate trial was not accomplished, and in another adequate pressure measurements were not obtained. Of the remaining 11, the ductus arteriosus was effectively dilated by PGE1 in 10 infants. This was evidenced by an increase in descending aortic blood pressures and a reduction in the pressure difference between the main pulmonary artery and descending aorta in six infants with aortic arch interruption and between ascending and descending aorta in four infants with coarctation. Lower body perfusion improved and left ventricular failure was improved. The infant who did not respond was 5 months old. There were no complications.

Aorta, Thoracic↗
PubMed1979

Morphological development of the pulmonary vascular bed in experimental pulmonic stenosis.

The main pulmonary trunk was banded in four fetal sheep at 63--69 days of gestation. The fetuses were killed after they had developed progressive pulmonary stenosis at 98, 123, 134 and 135 days of gestation. The right lung of each animal was perfused with glutaraldehyde and serial sections followed microscopically. The medial width/external diameter ratios for fifth generation resistance vessels were significantly less (0.13) than those from six normal control lungs (0.16, p less than 0.001). In addition, the number of resistance vessels per cm2 lung tissue in the lungs of the animals with experimental pulmonic stenosis was less than in normal controls. The altered in utero hemodynamics with severe pulmonic stenosis results in thin-walled pulmonary arterial vessels. This may be caused by an increased blood oxygen tension of the blood perfusing the pulmonary circulation via reversed flow through the ductus arteriosus, or altered pulmonary arterial pressure characteristics in the pulmonary vessels distal to the obstructed pulmonary trunk.

Animals↗