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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 127 records · Page 7Linked to original sources
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

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

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

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↗
PubMed1978

Cardiac output and its distribution and organ blood flow in the fetal lamb during ritodrine administration.

The response of the fetal circulation to beta adrenergic stimulation with ritodrine hydrochloride has been investigated by long-term monitoring of the fetal lamb in utero. Ritodrine was infused intravenously either into the ewe or directly into the fetus, and cardiovascular and acid-base responses were measured. Fetal cardiac output and its distribution were measured with the use of radionuclide-labeled microspheres. The output of each ventricle also was measured by means of long-standing implanted electromagnetic flow transducers around the ascending aorta or pulmonary trunk during infusion of ritodrine at various rates into the fetus. Infusion of ritodrine (1.9 mcg. per kilogram per minute) into the ewe caused no change in fetal heart rate, blood pressure, cardiac output, or umbilical blood flow, but did cause an increase in fetal adrenal and myocardial blood flow. Ritodrine infused directly into the fetus produced a marked increase in fetal heart rate and a minimal change in cardiac output. There were no significant changes in fetal or maternal acid-base balance during the ritodrine infusions.

Acid-Base Equilibrium↗
PubMed1978

Responsiveness of the lamb ductus arteriosus to prostaglandins and their metabolites.

The relative potencies of the prostaglandins A1, A2, E1, E2, F2alpha and their 15-keto-, 15-keto-13,14-dihydro-, and 13,14-dihydro-metabolites were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2. All the prostaglandins (except PGF2alpha and its 15-keto-metabolites) relaxed the tissue. However, only PGE1, E2, and their 13,14-dihydro-metabolites, were effective at concentrations below 10(-8) M. Therefore, events that alter metabolism of circulating PGs in the perinatal period may have significant effects on the relative patency or closure of the ductus arteriosus.

Animals↗
PubMed1978

Formation of prostacyclin (PGI2) by the ductus arteriosus of fetal lambs at different stages of gestation.

Prostaglandins appear to play a role in maintaining patency of the ductus arteriosus during gestation. Prostacyclin (PGI2) is the major product of prostaglandin biosynthesis in the lamb ductus arteriosus. This factor is both a vasodilator and a potent inhibitor of human platelet aggregation. We used inhibition of platelet aggregation as a sensitive bioassay to measure PGI2 generation in rings of ductus arteriosus from fetal lambs. Mechanical manipulation accelerated the rate of PGI2 released from the tissue 10 to 50 times. Tranylcypromine, an antagonist of prostacyclin synthetase, suppressed production of PGI2 by rings of ductus arteriosus. Rings from immature animals (98-103 days gestation, term is 150 days) released significantly more PGI2 (190 +/- 28 ng/g wet weight/ 20 min, n = 9) than did those from near term animals (136-146 days; 106 +/- 23 ng/g wet weight/20 min, n = 10). The capacity of the ductus arteriosus to generate more PGI2 earlier in gestation is consistent with the observation that vessels from animals less than 110 days gestation have a significantly larger indomethacin induced contraction than do vessels near term.

Animals↗
PubMed1978

Fetal hypertension and the development of increased pulmonary vascular smooth muscle: a possible mechanism for persistent pulmonary hypertension of the newborn infant.

Chronic pulmonary arterial hypertension was produced in six fetal lambs. In four (126 to 139 days' gestation) unilateral fetal renal artery constriction caused systemic arterial mean blood pressure elevations. In another fetus, constriction of the umbilical artery caused a systemic mean blood pressure elevation; in the sixth, partial occlusion of the ductus arteriosus caused isolated pulmonary arterial hypertension. The right lung of each fetus was perfused with fixative at the in vivo mean arterial pressure and the amount of smooth muscle in the fifth generation (resistance) vessels analyzed using the medial width/external diameter ratio. There was a significant increase in the medial width/external diameter ratio in the six experimental animals as compared to that in six normal fetuses. In separate fetuses the increased ratios were due to a decreased external diameter, increased smooth muscle, or both these factors. The total number of resistance vessels was counted in the right lung of each fetus and no significant difference from normal was observed. We postulate that either fetal systemic hypertension or constriction of the ductus arteriosus causes fetal pulmonary hypertension in utero and that this produces increased smooth muscle development in pulmonary arterial resistance vessels; this may be a pathogenic mechanism for the syndrome of persistent pulmonary hypertension of the newborn infant.

Animals↗