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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 73 records · Page 4Linked to original sources
PubMed1985

Recognition of fetal arrhythmias by echocardiography.

Fetal arrhythmias were detected in 33/198 high risk pregnancies from 21 weeks to term. Using the two-dimensional echocardiographic image of the fetal heart as a guide, the M-mode beam was directed to define the motion of the ventricular and atrial walls and atrioventricular valve or semilunar valves. Atrial contraction was defined either by the atrial wall motion or from the A-point of the atrioventricular valve. Ventricular contraction was defined by closure of the atrioventricular valve (C-point), the onset of ventricular wall contraction, or from the semilunar valve opening. Ladder diagrams of the sequence of atrial and ventricular activation were constructed to define the temporal sequence of these events. Premature atrial contractions were present in 12. In one fetus this arrhythmia converted into supraventricular tachycardia while in the other 11 fetuses the course was benign. Two fetuses had premature ventricular contractions. Supraventricular tachycardia was noted in five fetuses. One with hydrops at 29 weeks returned to sinus rhythm following maternal administration of procainamide. A second hydropic fetus with paroxysmal atrial tachycardia and hydrops failed to respond to digitalis, propranolol, procainamide, verapamil, or amiodarone, and died shortly after cesarean section. Two mature fetuses had tachycardia close to term and were treated after cesarean section. One fetus with runs of atrial tachycardia died in utero. Three fetuses had complete heart block, two of whom were from mothers with connective tissue diseases. In four fetuses, there was bradycardia of less than 100/minute lasting more than 30 seconds, but these episodes disappeared in 2 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1985

Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs.

We have created a totally synthetic, protein-free surfactant (Exosurf) composed of dipalmitoylphosphatidylcholine, hexadecanol, and tyloxapol. We studied the effects of endotracheal instillation of Exosurf on survival and pulmonary function of preterm lambs delivered at 131 to 133 days gestation (term 148 days). Exosurf treatment was compared with instillation of surface-active material prepared from lung lavages of adult sheep and with no instillation. Lambs were delivered by cesarean section, paralyzed, and mechanically ventilated. The Exosurf group survived longer (80% alive at 11 hours) than did the no instillation group (30% alive at 11 hours) (P less than 0.05). There were no statistically significant differences between the Exosurf and sheep surfactant groups. We conclude that Exosurf, a synthetic surfactant, produces significant improvement in survival and pulmonary function in preterm lambs.

Animals↗
PubMed1985

Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs.

The factors responsible for maintaining the normally low pulmonary blood flow and high pulmonary vascular resistance in the fetus are not well understood. Since leukotrienes are potent pulmonary vasoconstrictors in many adult animal species, we determined whether leukotrienes were perhaps involved in the control of the fetal pulmonary circulation by studying the effects of putative leukotriene end organ antagonists in two groups of fetal lambs. In six fetal lambs studied at 130-134 days gestation, FPL 55712 increased pulmonary blood flow by 61% (P less than 0.05) and reduced pulmonary vascular resistance by 45% (P less than 0.05). There was a small increase in heart rate but no changes in pulmonary and systemic arterial pressures and systemic arterial blood gases. In six other fetal lambs studied at 130-140 days gestation, FPL 57231 increased pulmonary blood flow by 580% (P less than 0.05) and decreased pulmonary vascular resistance by 87% (P less than 0.05). Pulmonary and systemic arterial pressures decreased (P less than 0.05), and heart rate increased (P less than 0.05). Leukotriene end organ antagonism significantly increases fetal pulmonary blood flow and decreases pulmonary vascular resistance. Leukotrienes may play a role in the physiological control of the fetal pulmonary circulation.

Animals↗
PubMed1985

Persistent responsiveness of the neonatal ductus arteriosus in immature lambs: a possible cause for reopening of patent ductus arteriosus after indomethacin-induced closure.

Reopening of the ductus arteriosus after successful indomethacin-induced closure has become a major problem with indomethacin treatment. In full-term human newborns and lambs, the ductus behaves like ischemic tissue after its initial constriction. Its ability to continue to relax or contract depends on the amount of left-to-right shunt through the ductus lumen. To see if ductus constriction in preterm lambs would produce the same loss of ductus responsiveness, we delivered 42 lambs by cesarean section and ventilated them for 6.6 +/- 0.5 (+/- SE) hr. We measured ductus arteriosus resistance and left-to-right shunt with the use of radionuclide-labeled microspheres. After the hemodynamic measurements were obtained, the ductus was studied in vitro. Immature lambs were more likely to have reactive ductus (after their initial ductus constriction) than were more mature lambs. This was due to a diminished degree of ductus constriction as well as persistence of ductus responsiveness in immature lambs when compared with more mature lambs. This persistence of ductus responsiveness in immature lambs after ductus constriction may account for the high reopening rate in preterm infants after successful indomethacin-induced closure.

Animals↗
PubMed1985

Autoregulation of cerebral blood flow in the preterm fetal lamb.

The purpose of the present study was to determine if autoregulation of cerebral blood flow (CBF) is present in the preterm fetal lamb and, if present, to measure the range of mean arterial blood pressure over which autoregulation exists. Thirty-seven measurements of CBF were made in seven preterm fetal lambs (118-122 days gestation) over a mean carotid arterial blood pressure (CBP) range of 18-90 mm Hg. CBF was measured by the radionuclide-labeled microsphere technique. CBP was altered by graduated inflation of balloons placed around the brachiocephalic trunk and the aortic isthmus. To eliminate the effects of reflex changes in heart rate, the carotid sinus and aortic nerve were ablated bilaterally. CBF was linearly related to mean CBP from 18-45 mm Hg, constant over a mean CBP of 45-80 mm Hg, and again linear from 80-90 mm Hg. Resting mean CBP (normotension) was 53.8 +/- 1.9 mm Hg during the control period and 51.7 +/- 0.8 mm Hg during the equilibration periods. This study demonstrates that although autoregulation of CBF is intact in the preterm fetal lamb, the range is narrowed compared to the term lamb and resting mean CBP lies close to the lower limit of autoregulation.

Animals↗
PubMed1985

Leukotriene inhibition prevents and reverses hypoxic pulmonary vasoconstriction in newborn lambs.

The effects of the leukotriene antagonist FPL 57231 on the circulation were studied in spontaneously breathing normoxic and hypoxic newborn lambs in order to evaluate the role of leukotrienes in the perinatal control of hypoxic pulmonary vasoconstriction. Hypoxia produced a 58% increase in pulmonary arterial pressure (p less than 0.05) and a 37% increase in pulmonary vascular resistance (p less than 0.05). Hypoxic pulmonary vasoconstriction was abolished by the prior infusion of FPL 57231. Pulmonary arterial pressure increased by only 8% and pulmonary vascular resistance decreased by 10% from normoxia. The infusion of FPL 57231 during hypoxia-induced pulmonary vasoconstriction reversed the increase in pulmonary arterial pressure (p less than 0.05) and pulmonary vascular resistance (p less than 0.05). The hypoxia-induced increase in cardiac output was maintained during the infusion of FPL 57231. Leukotrienes may play a significant role in the mediation of hypoxic pulmonary vasoconstriction. Leukotriene inhibition with FPL 57231 may be useful in the management of infants with persistent pulmonary hypertension syndrome.

Animals↗
PubMed1985

Developmental changes in myocardial contractile reserve in the lamb.

We have assessed serial changes in myocardial contractility and reserve in the normal lamb over the first month of life using an in vivo adaptation of the endsystolic pressure-volume relationship. Via a left thoracotomy, we insert a catheter tip pressure transducer into the left ventricle, affix an echo transducer onto the left ventricular epicardium, place an electromagnetic flow transducer around the pulmonary artery, and insert catheters for monitoring and infusions. We measure contractility by generating left ventricular wall stress-volume index (the cube of dimension) curves, at the same time increasing afterload by infusing phenylephrine. The slope of the endsystolic wall stress-volume index relationship is our index of contractility. Weekly studies were performed at rest and during isoproterenol infusion in 12 animals, and after propranolol administration in four. The data showed a progressive decrease in resting contractility but no change in maximal contractility during isoproterenol infusion over the 4 wk. Taking each week separately, the average increase in contractility during isoproterenol infusion was small at 1 wk (13%), moderate at 2 and 3 wk (24 and 26%, respectively), and large at 4 wk (79%). beta-Adrenergic blockade with propranolol caused a significant decrease in contractility in three of four animals studied at 1 wk, in only one of four animals at 2 wk, and in none of four animals at 3 or 4 wk. Thus, the newborn lamb shows a limited reserve in contractility that increases progressively with age; the limited reserve appears secondary to a high resting beta-adrenergic state.

Animals↗
PubMed1985

Chronic hypoxemia in the newborn lamb: cardiovascular, hematopoietic, and growth adaptations.

We have created a model of chronic hypoxemia in the newborn lamb by decreasing pulmonary blood flow in the presence of an atrial septal defect. Via a left lateral thoracotomy, we place an inflatable balloon around the pulmonary artery and perform an atrial septostomy under direct vision. We also insert several vascular catheters and place an electromagnetic flow transducer around the ascending aorta. Three days after surgery, we inflated the balloon in 11 lambs such that arterial oxygen saturation decreased to 60 to 75%. Studies were performed on these lambs twice weekly and weekly on 12 normoxemic lambs. Growth decreased sharply (47 +/- 123 versus 221 +/- 82 g/day) at the onset of hypoxemia and remained low, although oxygen consumption followed the normal gradual decline. Heart rate remained elevated throughout the study. Arterial PCO2 levels decreased from 40 +/- 5 to 35 +/- 7 torr and remained low. Systemic blood flow decreased at balloon inflation but quickly returned to normal. Mixed venous saturation was low, but could decrease further with shivering. Systemic oxygen delivery decreased initially but returned to normal as Hb concentration rose (from 9.4 +/- 1.5 to 12.5 +/- 2.2 g/dl). P50 increased normally over the study period. Four of the 11 hypoxemic lambs died during the study. These data show that, in the chronically hypoxemic newborn, systemic oxygen delivery is maintained primarily by a rising Hb. Total body oxygen consumption is maintained at rest but is redistributed away from anabolic requirements and toward cardiorespiratory work. This signal to decrease growth occurs despite less than maximal oxygen extraction at rest.

Animals↗
PubMed1985

Thromboxane is not responsible for the high pulmonary vascular resistance in fetal lambs.

The factors responsible for the high pulmonary vascular resistance in the fetus are not well known. Thromboxane (TX) A2 is a potent pulmonary vasoconstrictor. To determine whether TXA2 may play a role in fetal pulmonary vasoconstriction, we infused the specific TX synthetase inhibitor U63,557A into eight chronically instrumented fetal lambs (134-137 days gestational age, full term 145 days) and measured pulmonary blood flow, pulmonary and systemic arterial pressure, and heart rate. U63,557A (3 mg/kg as a bolus then 3 micrograms/kg/min for 120 min infused in the main pulmonary artery) did not change pulmonary blood flow, pulmonary mean arterial pressure, and pulmonary vascular resistance during the infusion and during 2 h following the end of the infusion. During the infusion, TXB2 arterial plasma concentrations decreased from 106.1 +/- 17.5 to 8.7 +/- 2.9 pg/ml. In three of the fetal lambs, immediately after the 2-h infusion of U63,557A, we infused the leukotriene end-organ antagonist FPL 57231 into the main pulmonary artery (1 mg/kg/min for 60 min). TXA2 synthesis inhibition did not prevent the pulmonary vasodilation induced by FPL 57231. Pulmonary blood flow increased from 64.8 +/- 24.4 to 669.5 +/- 65.6 ml/min/100 g lung tissue during the FPL 57231 infusion. We conclude that TXA2 does not play a role in the maintenance of elevated fetal pulmonary vascular tone, either directly or as a mediator of leukotriene action.

Animals↗
PubMed1984

Surgical treatment of truncus arteriosus in the first 6 months of life.

One hundred six infants were seen at the University of California Medical Center between 1974 and 1981 with the diagnosis of truncus arteriosus. One hundred of these underwent physiologic correction prior to 6 months of age. Six infants died prior to operation while undergoing intense medical therapy to improve their basic condition. There were 11 operative deaths with a mortality rate of 11%. Of the 86 long-term survivors, 55 have returned for conduit change because of either body growth or pseudointima proliferation of the conduit. There had been no mortalities at the time of conduit change, and 29 of these were repaired using a straight tube between the ventricle and pulmonary trunk, while 26 had valve conduits placed. Physiologic correction in the first 6 months of life has been accomplished with a low mortality rate and apparent good long-term results with none of the survivors having evidence of elevated pulmonary vascular resistance.

Blood Vessel Prosthesis↗
PubMed1984

Decreased contractility of the ductus arteriosus in experimental pulmonic stenosis.

Delayed closure of the ductus arteriosus after birth has been observed in newborn infants with critical pulmonic stenosis and in newborn lambs with experimental pulmonic stenosis. This delayed ductal closure may be caused by a decreased ability of the muscle to contract when exposed to oxygen or to an increased production of or sensitivity to prostaglandin (PG) E2, the endogenous ductus arteriosus vasodilator. To determine whether the abnormal hemodynamic pattern during fetal life associated with pulmonic stenosis alters the responsiveness of the ductus arteriosus, we operated on 10 fetal lambs of gestational ages 70 to 77 days (term is 148 days) and placed a band around the pulmonary artery. Catheterization at 137 to 142 days showed severe pulmonic stenosis. We then studied isolated rings of ductus arteriosus from these lambs. The oxygen-induced increase in tension in rings of ductus arteriosus from lambs with pulmonic stenosis was significantly decreased (2.55 +/- 0.38; n = 10) compared with rings from control lambs (4.03 +/- 0.51; n = 6, p less than .03). There was no difference between the two groups in either the amount of PGE2 released by the rings or in the sensitivity (expressed as median effective dose) of the rings to PGE2. There was also no difference in the increase in tension when endogenous PGE2 was inhibited by indomethacin. We conclude that delayed closure of the ductus arteriosus in lambs with experimental pulmonic stenosis is not caused by increased sensitivity to or production of PGE2 in the ductus arteriosus (as it is in premature lambs) but rather is the result of a diminished ability of the ductus arteriosus to contract when exposed to oxygen.

Animals↗
PubMed1984

Role of thyroid hormone in postnatal circulatory and metabolic adjustments.

To assess the role of the early postnatal surge in plasma thyroid hormone concentrations on cardiovascular and metabolic adaptations, we measured cardiac output, total oxygen consumption, and plasma triiodothyronine (T3) concentrations in three groups of lambs in the first 6 h after delivery. 15 fetal lambs were prepared at gestational ages of 128-129 d by placing catheters in the brachiocephalic artery, descending aorta, distal inferior vena cava, left atrium, and pulmonary artery so that measurements could be made soon after delivery. They were divided into three groups: Group I comprised five control animals; Group II consisted of five fetuses in which thyroidectomy was performed at surgery at 129 d gestation; and Group III consisted of five animals in which thyroidectomy was performed at term gestation during delivery by caesarian section, prior to severing the umbilical cord. The lambs in Group I exhibited a rapid postnatal rise in T3 concentrations, similar to that described previously, reaching a peak value of about 5 ng/ml. Although the postnatal surge in T3 concentration was arrested in Group II and III animals, Group II had no detectable plasma T3, while the Group III animals had T3 concentrations of about 0.8 ng/ml, which were within the range previously reported for term lamb fetuses. The lambs in group II showed 40-50% lower left ventricular outputs (190 vs. 297 ml/kg per min), systemic blood flows (155 vs. 286 ml/kg per min), and oxygen consumptions (9.8 vs. 20.2 ml/kg per min) as compared with Group I animals over the entire 6-h period. The lambs in Group II also had significantly lower heart rates (131 vs. 192 beats/min) and mean systemic arterial pressures (56 vs. 72 torr). However, there were no significant differences for any of these measurements between the Group III and Group I lambs. The reduction in cardiac output in the Group II animals were reflected in a significantly lower blood flow to the peripheral circulation, but there were no significant differences in blood flow to other organs in the three groups. These studies indicate that plasma thyroid concentrations in the 2-3 wk prior to delivery and not the increase in thyroid hormone concentrations which occur after birth are important for postnatal cardiovascular and metabolic adjustments. We speculate that lack of circulating triiodothyronine in late gestation may affect postnatal cardiovascular adaptation by modifying normal beta adrenergic receptor development.

Animals↗
PubMed1984

Effects of nitroprusside on cardiac function, blood flow distribution, and oxygen consumption in the conscious young lamb.

Resting cardiac output is high relative to body weight during the neonatal period and there is a limited reserve for further increasing cardiac output. We assessed the effect on the circulation of reducing peripheral vascular resistance by infusing high doses of sodium nitroprusside in 1- and 3-week-old lambs. In a dose of 5 micrograms X kg-1 X min-1 over 1 h, nitroprusside caused a decrease in aortic and left atrial pressure, an increase in heart rate, and no significant changes in cardiac output or oxygen consumption. Infusing 10 micrograms X kg-1 X min-1 for 2 h resulted in an initial marked decrease in aortic pressure, cardiac output, and also heart rate. Within 50 min aortic pressure gradually increased, but was still well below control levels, while cardiac output returned to control level and heart rate slowly increased. Distribution of cardiac output and organ blood flows was measured by the radionuclide microsphere method. Blood flows to the kidneys and to the skin fell markedly, but flows to other organs did not change significantly.

Aging↗
PubMed1984

The effects of tolazoline on the distribution of cardiac output in normoxemic and hypoxemic lambs.

We measured cardiac output and its distribution (microspheres), blood gases and pH, heart rate, and pulmonary and aortic pressures in three groups of 1- to 3-day-old lambs. Group I consisted of six animals who had these measurements made during both control (normoxemic) and hypoxemic (PaO2 25 +/- 3 mm Hg) periods. Hypoxemia increased the pulmonary artery pressure 70% (p less than 0.01). This elevation in pulmonary arterial pressure lasted as long as the animals were hypoxemic (90 min). Hypoxemia had no effect on cardiac output, mean systemic arterial pressure, heart rate, or the rate-pressure product of the left ventricle. Blood flow to the heart increased an average of 228% (p less than 0.05); flow to the brain increased 233% (p less than 0.05); flow to the skin decreased 35% (p less than 0.05) after 60 and 90 min of hypoxemia. Blood flow to the remaining organs was uneffected by hypoxemia. Group II consisted of four animals who were given 1, 5, and 10 mg/kg/h of tolazoline (Priscoline) intravenously while normoxemic. There was no effect on the pulmonary arterial pressures or blood gases and pH. Tolazoline (5 and 10 mg/kg/h) reduced systemic arterial pressures an average of 22% (p less than 0.05). Tolazoline (1 mg/kg/h) reduced blood flow to the spleen 48% and that to the brain by 20% and increased flow to the body 32% (p less than 0.05). Five mg/kg/h of tolazoline decreased renal and brain blood flow 35 and 20%, respectively (p less than 0.05) while that to the body and liver increased 26 and 48% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2.

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Animals↗