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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 91 records · Page 5Linked to original sources
PubMed1983

Developmental changes in oxygenation and circulatory responses to hypoxemia in lambs.

We studied moderate [fractional inspired O2 (FIO2) 0.09] and severe (FIO2 0.06) hypoxemia in 21 lambs (group 1, 1 wk old; group 2, 3-4 wk old; group 3, 5-7 wk). With moderate hypoxemia, all groups increased heart rate, cardiac output, and pulmonary arterial pressure and decreased systemic and pulmonary vascular resistance; cardiac output and pulmonary arterial pressure increases were less in group 1, because of higher resting values. With severe hypoxemia, heart rate increased similarly, cardiac output was unchanged, and aortic pressure fell associated with severe metabolic acidosis or arrhythmias. Regional blood flow changed similarly in all groups; heart and brain flow increased, carcass flow was unchanged, and skin, GI tract, and kidney flow fell. O2 consumption (VO2) and mixed venous PO2 decreased, though O2 saturation was higher in group 1 due to the lower O2 half-saturation pressure of hemoglobin. With a given decreased VO2 there was more metabolic acidosis in older lambs and an increased VO2 after termination of hypoxemia, suggesting greater O2 debt. As in the fetus, young lambs are better able to tolerate a decreased VO2 than older lambs.

Aging↗
PubMed1983

Factors determining the loss of ductus arteriosus responsiveness to prostaglandin E.

The ductus arteriosus of the newborn infant varies in its ability to dilate when doses of prostaglandin E (PGE) are administered. We infused PGE2 into 15 late-gestation newborn lambs to determine which factors regulate the ability of the ductus arteriosus to respond to PGE. PGE2 dilated the ductus in 10 lambs (responders); in five other lambs, despite similar PGE2 concentrations, there was no effect (nonresponders). The measured ductus resistance after the PGE2 infusion was directly related to the ductus resistance before the infusion. Responders had a larger left-to-right shunt through the ductus before the PGE infusion than nonresponders. Ductus that were isolated and studied in vitro from lambs that were nonresponsive to PGE2 (in vivo) were limited in their ability to relax with PGE2 as well as to actively contract with oxygen and indomethacin. This generalized loss of ductus responsiveness was directly related to the amount of the left-to-right shunt through the lumen of the ductus. These observations are consistent with the hypothesis that the constriction of the ductus arteriosus after birth limits the ability of the ductus to respond to PGE therapy.

Animals↗
PubMed1983

Effects of ambient temperature on oxygen consumption and the circulation in newborn lambs at rest and during hypoxemia.

To assess the effects of environmental temperature on responses to hypoxemia, we studied five unsedated lambs in the first week after birth. We catheterized the carotid artery and pulmonary artery (via the jugular vein). After recovery of at least 1 day, we measured pH, blood gases, arterial and mixed venous blood O2 content, oxygen consumption (VO2), heart rate, carotid and pulmonary arterial pressures, and cardiac output in both warm (25 degrees C) and cool (17.4 +/- 1.1 degree C) environments. In the cool environment, with no shivering, VO2 increased 40% (14.9 to 20.8 ml/kg/min). There were also increases of arteriovenous blood O2 content difference of 19%, cardiac output of 18%, and heart rate of 14%. In four lambs, we studied the same variables during hypoxemia (FiO2 = 0.09 for 1 h) at both temperatures. In the cool environment, hypoxemia produced a greater fall of VO2 (26% versus 6%) and arteriovenous oxygen differences (30% versus 19%) and a smaller increase of cardiac output (8% versus 14%) and heart rate (26% versus 43%). Also in the cool environment, core temperature decreased more (2.1 versus 0.4 degree C), but base deficit was the same (-6 versus -5 mEq/liter). Despite the greater fall in VO2 during hypoxemia in the cool environment, the lowest value achieved was still higher than the level during normoxemia in the warm environment. Similarly, cardiac output during hypoxemia was greater in the cool than in the warm environment. These findings may explain the variability in reported normal resting values and responses to hypoxemia. Contrary to previous reports, they also indicate that during severe hypoxemia neonates have a decreased reserve of metabolic and cardiovascular responses in a cool compared with a warm environment.

Animals↗
PubMed1983

Cardiovascular responses to alpha-melanocyte stimulating hormone during the perinatal period in sheep.

To determine the effects of alpha-melanocyte stimulating hormone (alpha MSH) on the circulation of undisturbed fetal sheep and young lambs and to explore possible mechanisms of actions, we examined the responses of ascending aortic blood flow, heart rate, stroke volume, and arterial blood pressure to a single intravenous injection of alpha MSH, ACTH, cortisol and to alpha MSH after beta-adrenergic blockade. We also measured cardiac output and organ blood flows before and after alpha MSH injection by the radionuclide labeled microsphere technique. alpha MSH increased ascending aortic blood flow from 249 +/- 23 to 327 +/- 30 ml X min-1 X kg-1 (P less than 0.001), heart rate from 111 +/- 10 to 126 +/- 11 min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-day-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-days-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and from 77.5 +/- 4.5 to 72.7 +/- 4.3 mmHg (P less than 0.001) in young lambs. In six additional young lambs (20-35-day-old) cardiac output, measured by microspheres, increased with alpha MSH from 216 +/- 20 to 261 +/- 19 ml X min-1 X kg-1 (P less than 0.001). alpha MSH also increased blood flow to the myocardium from 104 +/- 22 to 151 +/- 26 ml X min-1 X 100 g-1 (P less than 0.001), to the adrenals from 195 +/- 38 to 243 +/- 41 ml X min-1 X 100 g-1, (P less than 0.05), and to the lungs from 157 +/- 31 to 468 +/- 81 ml X min-1 X 100 g-1 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

The developmental effects of prostaglandin D2 on the pulmonary and systemic circulations in the newborn lamb.

Prostaglandin D2 (PGD2) lowers pulmonary arterial blood pressure without changing systemic arterial blood pressure in fetal and newborn lambs but increases pulmonary arterial pressure in older animals. We investigated the effect of PGD2 on the circulation in 15 newborn lambs, some studied intermittently from 1 to 30 days of age, with induced pulmonary arterial hypertension. PGD2 was infused intravenously in doses of 1 to 25 micrograms/kg per min. During the first 3 days of life, a 5 micrograms/kg per min infusion decreased mean pulmonary arterial pressure by 33.9%, increased mean systemic arterial pressure by 11.5% and increased cardiac output by 7.3%. After 15 days of age there was a 10.7% increase in mean pulmonary arterial pressure, a 1.8% decrease in mean systemic arterial pressure and a 6.1% increase in cardiac output. Pulmonary vascular resistance decreased by 38.2% in the first 3 days of life but increased by 9.9% after 15 days of life. With this progressive pulmonary vasoconstriction, there was systemic vasodilation with advancing age. Similar age specific effects were seen with 1 and 25 micrograms/kg per min infusions. The specificity of PGD2 for the pulmonary circulation and the attenuation of its vasodilating properties during the first week of life suggests that PGD2 may be important in the regulation of pulmonary vascular resistance and pulmonary blood flow during the immediate perinatal period.

Animals↗
PubMed1982

Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants.

We performed a double-blind, controlled study of prophylactic indomethacin therapy in 47 premature infants (less than 1700 g) who had subclinical patent ductus arteriosus. They received either indomethacin or placebo at a mean age of 2.9 days. Among the 25 infants weighing more than 1000 g, a hemodynamically important ductus shunt developed in only four of the 14 given placebo. The incidence of important shunts, the number of surgical ligations, and the duration of oxygen therapy were not appreciably different between the study groups. In contrast, among the 22 infants who weighed 1000 g or less, a major ductus shunt developed in 10 of the 12 given placebo. In the smaller infants indomethacin therapy was associated with a significantly lower incidence of major shunts, fewer surgical ligations, a decreased duration of oxygen therapy, and fewer days necessary to regain birth weight. We conclude that prophylactic indomethacin therapy in infants weighing under 1000 g prevents the later development of large ductus shunts and decreases morbidity.

Clinical Trials as Topic↗
PubMed1982

Prostaglandin D2 reverses induced pulmonary hypertension in the newborn lamb.

We investigated the effects of PGD2 in six near-term newborn lambs with induced pulmonary hypertension (mean pulmonary arterial pressure equal to mean systemic arterial pressure). In each lamb PGD2 decreased mean pulmonary arterial pressure, increased pulmonary blood flow, and therefore decreased pulmonary vascular resistance without changing mean systemic arterial pressure. A bolus dose of 20 micrograms PGD2 decreased pulmonary arterial pressure by 30%, increased pulmonary blood flow by 45%, and decreased pulmonary vascular resistance by 54%; systemic arterial pressure increased by 4%. At all doses, pulmonary vascular resistance fell further than systemic vascular resistance, the ratio of percent change in pulmonary vascular resistance to percent change in systemic vascular resistance was approximately 2:1. Similar changes occurred with continuous infusions of PGD2. These effects suggest a role for PGD2 in the normal regulation of pulmonary vascular resistance and blood flow at birth. In addition, because PGD2 in these circumstances increases pulmonary blood flow and reduces pulmonary arterial pressure, it may merit further trials in nonhuman primates; it may be an appropriate agent for treating newborn infants with persistent pulmonary hypertension.

Animals↗
PubMed1982

A new technique for perfusion fixation and contrast enhancement of foetal lamb myocardium for electron microscopy.

A technique of perfusion fixation following elective diastolic cardiac arrest was developed to obtain excellent preservation of foetal lamb hearts for morphological studies with electron microscopy. A technique was developed to markedly enhance the contrast of embedded material by treating thin sections with tannic acid prior to lead staining. This technique has been particularly useful for quantitative morphometric analysis.

Animals↗
PubMed1982

Fetal myocardial oxygen and carbohydrate consumption during acutely induced hypoxemia.

Two days after catheter placement we measured the heart rate, arterial blood pressure, myocardial blood flow, and the myocardial consumption of oxygen, glucose, lactate, and pyruvate in 11 fetal sheep in utero. We then administered 8-10% oxygen to the ewe, producing a 50% decrease in oxygen content in the fetal ascending aortic blood. After 15 min of hypoxemia we repeated the measurements. Oxygen content in the fetal coronary sinus blood decreased significantly, but the arteriovenous difference of oxygen across the left ventricle also decreased during hypoxemia. Fetal myocardial blood flow increased 160% above the control level, and the myocardial oxygen consumption did not change. The systolic arterial blood pressure increased and the heart rate decreased, but cardiac work, as estimated by the rate-pressure product, was unchanged. As both fetal myocardial oxygen consumption and cardiac work did not change, myocardial oxygenation, the relationship between oxygen consumption and cardiac work, appears to be unchanged during this degree of hypoxemia. Although arterial blood glucose, lactate, and pyruvate concentrations increased significantly during hypoxemia, only the myocardial consumption of pyruvate increased; the arteriovenous difference of glucose and lactate decreased in proportion to the increase in myocardial blood flow. During hypoxemia, glucose consumption did not change, and lactate continued to be consumed rather than produced; thus it is apparent that fetal myocardial metabolism continued to be aerobic during this degree of hypoxemia. Complete oxidative combustion of the quantities of carbohydrates that were consumed would supply all of the substrate necessary to meet fetal myocardial energy demands both at rest and during hypoxemia.

Animals↗
PubMed1982

Regional myocardial blood flow and oxygen delivery in fetal, newborn, and adult sheep.

We measured and calculated their product, regional myocardial oxygen delivery, in unanesthetized, previously instrumented fetal, newborn, and adult sheep. In the fetus, blood flow and oxygen delivery were greater to the right ventricular free wall than to the left ventricular free wall. In the left ventricular free wall oxygen delivery increased significantly after birth and later decreased to a level in the adult that was similar to that of the fetus. There was a progressive decrease in oxygen delivery to the right ventricular free wall during the developmental period that we studied. Although the inner-to-outer blood flow ratio was significantly lower for the left and right ventricular free walls of the fetuses as compared with the newborns and adults, the ratio was greater than one in all three groups for both of the ventricular free walls. These data demonstrate that the changes that occur in the circulation after birth are associated with significant alterations in right and left ventricular myocardial blood flow and oxygen delivery, which most likely reflect changes in regional myocardial metabolic demands. In addition, there are further significant changes in regional myocardial blood flow during the transition from the newborn to adult hemodynamics.

Aging↗
PubMed1982

Long-term results after atrial repair of transposition of the great arteries in early infancy.

Fifty-two patients younger than age 100 days who had an intact interventricular septum or a small ventricular septal defect underwent atrial repair of d-transposition of the great arteries (d-TGA). No patient died. To assess long-term results, we evaluated all 36 patients who had been followed for at least 1.5 years (mean 2.7 years) after surgery. The physical findings, chest roentgenograms, ECGs and echocardiograms were reviewed. Catheterization was done 6-60 months (mean 15 months) after surgery in 28 patients. Growth was normal in all but three patients. Neurologic development was abnormal in six patients (delayed speech in one patient, learning disability in three patients and preoperative cerebral infarction in two patients). The ECG showed sinus rhythm in 24 patients, minor abnormalities in nine and major dysrhythmias in three. Catheterization showed a normal cardiac index in all 28 patients. No intracardiac shunt was detected in 19 of 24 patients in whom complete oximetry data were available. One patient required reoperation for persistent atrial shunt and subsequent pacemaker placement. Two patients required baffle revision for symptoms related to superior vena caval obstruction. Right ventricular end-diastolic pressure was less than 15 mm Hg in all of 18 patients evaluated. We conclude that atrial repair of d-TGA in early infancy can be performed with a low mortality rate and a low incidence of late complications.

Arteries↗
PubMed1982

Comparison of methods of measuring cardiac output in newborn lambs.

To define agreement between methods, we measured cardiac output (CO) in chronically instrumented lambs by four different methods. In 23 lambs we measured CO simultaneously by the Fick and microsphere methods and with an electromagnetic flowmeter over a wide range of CO (80-454 ml/kg/min) in different experimental conditions on 97 occasions. When the electromagnetic flowmeter was corrected for coronary flow (about 8% of CO) calculated from microspheres, the mean cardiac outputs were almost identical for these three methods (237, 235, and 236 ml/kg x min, respectively). Comparisons between any two of the methods showed a correlation coefficient greater than 0.89. In four lambs, 52 measurements of CO by Fick and thermodilution had a correlation coefficient of 0.94. We conclude that any of the four methods, if appropriately applied, adequately measures CO in a variety of circumstances and may be used with confidence for physiologic or other studies.

Animals↗
PubMed1982

Recovery of cardiovascular function in newborn lambs after thoracotomy.

Knowledge of the quality and speed of recovery after thoracotomy is crucial for studies of the early changes in cardiovascular function in the neonatal period. We studied the early recovery period after thoracotomy with pericardiotomy, but without ventriculotomy, in 21 lambs operated on between 2-24 days after birth. In 15 lambs, we measured resting pH,, PaO2, PaCO2, O2 consumption, cardiac output, heart rate, and aortic and pulmonary arterial pressures, before and after thoracotomy, daily for 1 wk. We found that, except for PaO2 (82 versus 87 torr), all variables returned to normal by the third day after thoracotomy. Four lambs were exposed to hypoxia (FIO2 0.09 for 1 h) before and 3 days after thoracotomy; hypoxia-induced changes were not different at the two different periods. Six other lambs, undergoing thoracotomy within the first 3 days after birth and exposed to hypoxia on the third postoperative day, had hypoxia-induced responses similar to six age-matched nonthoracotomized lambs. These findings indicate recovery of cardiovascular function by 48-72 h after thoracotomy. We believe, therefore, that reliable studies of the circulation in lambs are possible as early as 3-4 days after birth, even if thoracotomy is required for making measurements.

Age Factors↗
PubMed1981

Selective distribution of microspheres injected into the umbilical veins and inferior venae cavae of fetal sheep.

To investigate the extent of streaming of umbilical venous blood in the venous and arterial circulations of normal and hypoxic sheep fetuses and to experimentally determine its effect on determinations of blood flow by means of the microsphere method, we injected 15 mu microspheres labeled with different radionuclides into the umbilical veins (UVs) and distal inferior venae cavae (DIVC) of 21 chronically catheterized near-term sheep fetuses. We determined the ratio of the radioactive counts from the UV-injected microspheres to the radioactive counts from the DIVC-injected microspheres (UV/DIVC count ratio) in each fetal tissue in 40 experiments. In 75% of the normal fetuses and 58% of the hypoxic fetuses, UV-injected microspheres streamed preferentially through the foramen ovale to the left atrium and ventricle when compared with DIVC-injected microspheres. Fetal hypoxia was associated with a significant decrease in the extent of preferential streaming. In the arterial circulation, we found no evidence for preferential streaming of UV-injected and DIVC-injected microspheres.

Animals↗