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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 55 records · Page 3Linked to original sources
PubMed1988

Indomethacin and patent ductus arteriosus: effects on renal function in preterm lambs.

To examine the independent effects of a patent ductus arteriosus and of indomethacin therapy on the renal function of the preterm newborn, we created a preterm lamb model in which ductus diameter could be regulated. We studied 24 preterm newborn lambs. Eight lambs (group 1) had their ductus closed at delivery and received no indomethacin. Eight lambs (group 2) had their ductus closed and then received indomethacin (0.3 mg/kg) at 5.5 h; eight lambs (group 3) had their ductus kept open and then received indomethacin at 5.5 h. Hemodynamic and renal function measurements were made at 5 h (pretreatment) and at 12.5 h. In group 2 lambs there was a significant reduction in inulin clearance (GFR) and osmolal clearance after indomethacin. In contrast, lambs with an open ductus (group 3), when compared with lambs with a closed ductus (groups 1 and 2) at 5 h, already had significantly decreased blood pressure, GFR, urine volume, and osmolal clearance. Following indomethacin treatment, group 3 lambs showed no further decrease in renal function. We suggest that in preterm lambs with patent ductus, the apparent lack of renal dysfunction following indomethacin treatment reflects underlying diminished renal function.

Animals↗
PubMed1988

Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs.

We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery.

Acute Disease↗
PubMed1987

Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.

We created a model for studying the cardiovascular and pulmonary effects of patent ductus arteriosus (PDA) in premature lambs with respiratory distress. In 47 fetal lambs at 129 to 133 days gestation (term, 145 days), we infiltrated the ductus arteriosus with formalin and placed a mechanical occluder about it so that its patency could be regulated. Two days later the lambs were delivered, given sheep surfactant, paralyzed, and their lungs mechanically ventilated. These premature lambs could more than double their left ventricular output when challenged with increasing degrees of left-to-right shunts through the PDA. This was accomplished by an increase in stroke volume, not by an increase in heart rate. During the 40-minute observation period, there was no change in dynamic compliance or functional residual capacity while the ductus was patent. When the ductus was patent, there was a significant increase in arterial PaO2 (even with small left-to-right shunts) and a decrease in PaCO2 (with large shunts). Despite the heart's ability to handle the increased volume load of a PDA, there were significant alterations in individual organ blood flows, resulting from a combination of decreased perfusion pressure and localized vasoconstriction. The abdominal organs had significant reductions in blood flow even with small PDA shunts. This decrease in organ blood flow may explain some of the pathophysiologic manifestations of PDA in preterm infants.

Animals↗
PubMed1987

The cardiovascular effects of isoflurane in lambs.

The effects of 1.0 and 1.5 minimum alveolar concentrations (MAC) of isoflurane on mean systemic arterial pressure, heart rate, stroke volume, cardiac output, total body oxygen consumption, myocardial oxygen consumption, and regional distribution of blood flow were studied in newborn lambs. Fractional extraction of oxygen for the total body and for the myocardium were calculated. MAC for isoflurane was first determined in eight lambs less than 10 days old. The mean value obtained was 1.51%. Six different lambs were used for cardiovascular study. Heart rate, stroke volume, cardiac output, and mean systemic arterial pressure decreased significantly during isoflurane anesthesia. Mean systemic arterial pressure and cardiac output decreased in a dose-dependent manner. Heart rate decreased significantly at 1.0 MAC isoflurane, but no further at 1.5 MAC. Stroke volume decreased only at 1.5 MAC. Cardiac output and total body oxygen consumption decreased by similar amounts at 1.0 MAC. Although cardiac output fell further at 1.5 MAC, oxygen consumption did not. Fractional extraction of oxygen increased only at 1.5 MAC. Myocardial blood flow and oxygen consumption decreased in parallel at 1.0 MAC, with no significant change during 1.5 MAC. Myocardial fractional oxygen extraction did not change. Although blood flow to all six body regions decreased significantly from control at both concentrations of isoflurane, blood flow to all organs except the adrenal did not differ significantly during 1.0 and 1.5 MAC. The authors conclude that a decrease in oxygen requirement during isoflurane anesthesia results in an appropriate decrease in oxygen delivery, with no apparent diversion of cardiac output from non-vital to vital organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Respiratory effects of a patent ductus arteriosus in premature newborn lambs.

We examined the respiratory effects of a patent ductus arteriosus in 29 premature lambs (131-135 days gestational age) after infiltrating the ductal wall with formaldehyde solution (Formalin) and placing a snare around the ductus to regulate its patency. The lambs were given sheep surfactant, paralyzed, and mechanically ventilated at birth. We first compared 8 lambs with open ductus and 13 lambs with closed ductus during the 12 h after birth. Although lambs with open ductus had greater pulmonary blood flow (301 +/- 36 vs. 188 +/- 11 ml.min-1.kg-1, mean +/- SE, at 12 h of age) and mean pulmonary arterial (44 +/- 3 vs. 33 +/- 2 mmHg) and left ventricular end-diastolic (6 +/- 0.6 vs 4 +/- 0.7 mmHg) pressures, we found no differences in dynamic respiratory compliance (Cdyn = 0.55 +/- 0.07 vs. 0.55 +/- 0.03 ml.cmH2O-1.kg-1), midtidal volume resistance (62 +/- 5 X 10(-3) vs. 62 +/- 7 X 10(-3) cmH2O.ml-1.s), or functional residual capacity (FRC = 27 +/- 3 vs. 26 +/- 2 ml.kg-1). Alveolar-arterial PO2 difference was lower in the lambs with open ductus (238 +/- 65 vs. 362 +/- 37 Torr). Next, we challenged eight lambs with two separate saline infusions (50 ml.kg-1 over 3 min), each given with the ductus alternately closed or open. When the ductus was closed, FRC was unchanged, but Cdyn increased by 18% immediately after the infusion. When the ductus was open, FRC decreased by 16% and Cdyn decreased by 12%. We conclude that the premature lamb is surprisingly resistant to changes in respiratory function from ductal patency during the immediate neonatal period.

Animals↗
PubMed1987

Postnatal regulation of the pulmonary circulation: a role for lipid mediators?

The action and interaction of many products of arachidonic acid metabolism can affect the pulmonary circulation in the perinatal period. The rapid increase in pulmonary blood flow with the onset of ventilation likely is brought about to a large degree by the production locally of prostaglandin I2 (PGI2). This can be stimulated by purely mechanical factors, by the normally increasing concentrations of angiotension II, by the 02-mediated release of bradykinin, or perhaps by other phenomena. Prostaglandin D2 release from mast cells also may play some role. The opposing pulmonary vascular effect, i.e., pulmonary vasoconstriction, of leukotrienes is likely to play a role in regulating fetal pulmonary blood flow. Inhibition of the production or action of these substances will allow for vasodilatation, and it is probable that perinatal pulmonary vascular tone reflects a balance between local prostaglandin and leukotriene production.

Animals↗
PubMed1987

The differential effects of leukotriene C4 and D4 on the pulmonary and systemic circulations in newborn lambs.

Leukotriene (LT) C4 or D4 may mediate pulmonary hypertension induced by hypoxia. LT have also been isolated from patients with persistent pulmonary hypertension of the newborn syndrome and the adult respiratory distress syndrome. To compare the effects of LTC4 and D4 on the pulmonary and systemic circulations, we performed dose-response studies on spontaneously breathing newborn lambs. To determine whether the hemodynamic effects of LT are mediated through alpha-adrenergic stimulation, some lambs were pretreated with the alpha-adrenergic antagonist phentolamine mesylate before LT injection. These results were compared to the effects of pretreatment with the LT receptor antagonist FPL57231. To determine whether the LT-induced decrease in cardiac output was mediated by the decrease in heart rate, other lambs had their heart rate maintained by left atrial pacing. We found that LTC4 and D4 increased systemic arterial pressure and decreased cardiac output and heart rate. However, LTD4, but not LTC4, increased pulmonary arterial pressure. The hemodynamic effects of LTC4 and LTD4 were completely blocked by FPL57231 but not by phentolamine mesylate. Maintenance of heart rate by left atrial pacing did not alter the LT-induced decrease in cardiac output. We conclude that LTC4 and D4 have similar effects on the systemic circulation. However, LTD4 produces more pulmonary vasoconstriction. Because FPL57231 did block the pulmonary vasoconstriction caused by LT, LT antagonists may be useful in treating patients with pulmonary hypertension.

Animals↗
PubMed1987

Piriprost: a putative leukotriene synthesis inhibitor increases pulmonary blood flow in fetal lambs.

Leukotrienes may control fetal pulmonary vascular tone since infusions of putative leukotriene receptor antagonists markedly increase pulmonary blood flow and decrease pulmonary vascular resistance in fetal lambs. This hypothesis would be strengthened if inhibition of leukotriene synthesis also produced similar hemodynamic changes. We therefore studied the effects of piriprost (U 60257), a putative leukotriene synthesis inhibitor, on thirteen fetal lambs at 137 to 140 days gestation. In preliminary studies in four fetal lambs, doses of U 60257 greater than 20 mg/kg increased pulmonary blood flow. In the nine other fetal lambs, U 60257 (31.7 +/- 4.1 mg/kg) increased pulmonary blood flow by 502% (p less than 0.05) and decreased pulmonary vascular resistance by 87% (p less than 0.05). Pulmonary arterial and left atrial pressures were unchanged. Descending aortic pressure was increased (p less than 0.05) and heart rate was decreased (p less than 0.05). The abilities of both putative leukotriene synthesis inhibitors and leukotriene receptor antagonists to similarly increase fetal pulmonary blood flow and decrease pulmonary vascular resistance are consistent with the hypothesis that leukotrienes play a role in regulating fetal pulmonary vascular tone.

Animals↗
PubMed1987

Redistribution of regional blood flow and oxygen delivery in experimental cyanotic heart disease in newborn lambs.

Redistribution of regional blood flow is an important compensatory response to acute hypoxemia which preserves oxygen delivery to the most vital organs. It is not known if this change in blood flow persists when hypoxemia is prolonged, as occurs in cyanotic congenital heart disease. Chronic hypoxemia was produced in newborn lambs by creating pulmonary stenosis and an atrial septal defect. Oxygen saturation was maintained at 60-70% of control for 2 wk. Distribution of cardiac output was then measured with radionuclide-labeled microspheres. As compared with control, chronic hypoxemia did not alter total cardiac output. Regional blood flow was redistributed, however, the pattern of this redistribution was different from that seen during acute hypoxemia. Myocardial and cerebral blood flows, which increase during acute hypoxemia, return to control levels during chronic hypoxemia. Renal, splenic, gastrointestinal, carcass, and skin blood flows remain decreased. Hemoglobin gradually increases so that after 2 wk of hypoxemia total systemic oxygen delivery returns toward control. However, oxygen delivery to all organs except the heart and brain is reduced. Thus, although cardiac output and total systemic oxygen delivery return toward normal during chronic hypoxemia, these measurements may not reflect important regional variations in blood flow and oxygen delivery. Decreased oxygen and substrate delivery to the gastrointestinal tract, liver, and carcass may account for the alterations of metabolism and growth seen in the newborn with cyanotic congenital heart disease.

Animals↗
PubMed1987

How a patent ductus arteriosus effects the premature lamb's ability to handle additional volume loads.

A model of patent ductus arteriosus in premature lambs was created to examine the lamb's ability to handle the volume load imposed by a patent ductus arteriosus and to determine the lamb's ability to handle any additional volume load. Fifteen preterm lambs [133 +/- 2 (+/- SD) days gestation, term 145 days], whose ductal diameter could be regulated with a mechanical occluder, were studied to determine the independent effects of ductus patency and a saline volume load (50 ml/kg over 3 min) on left ventricular output and its distribution. During a saline infusion, preterm lambs with a closed ductus could only increase their stroke volume by 40% above baseline stroke volume. When challenged with a saline infusion, lambs with an open ductus still were able to increase their stroke volume significantly; the maximal increase in stroke volume during the saline load with the ductus open was 70% above baseline stroke volume. We hypothesize that the associated reduced left ventricular afterload plays a significant role in the preterm lamb's ability to increase its stroke volume when challenged with a patent ductus arteriosus. Even with a patent ductus arteriosus, the lamb still has the ability to handle additional volume loads.

Animals↗
PubMed1987

Prostaglandins and leukotrienes in the perinatal period.

Arachidonic acid is the precursor of many physiologically active substances. One such group, the prostaglandins, is involved in regulation of the ductus arteriosus, the perinatal pulmonary circulation, and uterine function. Administration of these substances or inhibition of their production or effect has therapeutic benefit in many different circumstances. Another group, the leukotrienes, also appears to be involved in regulation of the perinatal pulmonary circulation; pharmacologic manipulation of these has not yet been tried.

Ductus Arteriosus↗
PubMed1987

Umbilical cord compression produces pulmonary hypertension in newborn lambs: a model to study the pathophysiology of persistent pulmonary hypertension in the newborn.

We investigated the effects of chronic intrauterine hypoxaemia produced by prolonged partial umbilical cord compression on the circulation shortly after birth in lambs. Vascular catheters were inserted in 10 fetal sheep at 120 to 130 days gestation to measure descending aortic blood gases, arterial pH, and arterial O2 saturation. An inflatable silicone rubber balloon cuff was also placed around the umbilical cord. After recovery and the return of descending aortic blood gases to the normal range, the balloon was gradually inflated, decreasing the PaO2 from 21.2 +/- 3.6 to 17.5 +/- 1.3 mm Hg and the arterial O2 saturation from 57.1 +/- 9.2% to 37.2% +/- 5.2. After 14.3 +/- 3.7 days of partial umbilical cord compression, the lambs were delivered by Caesarean section, instrumented to measure systemic and pulmonary arterial, right atrial and pulmonary arterial wedge pressures, pulmonary and systemic blood flows, and mechanically ventilated. Five normal lambs were also studied. From 60 to 120 min after delivery, when compared to normal lambs, the umbilical compression lambs had an increased pulmonary arterial pressure (P less than 0.05) pulmonary vascular resistance (P less than 0.05), and right atrial pressure (P less than 0.05) with similar arterial blood gases. In both groups, hypoxic ventilation produced an increase in pulmonary arterial pressure (P less than 0.05) which on return to room air ventilation decreased to baseline in the normal lambs but not in the umbilical cord compression lambs (P less than 0.05). Prolonged partial umbilical cord compression produces chronic fetal hypoxaemia and pulmonary arterial hypertension after birth. This may represent a model to study the pathophysiology of persistent pulmonary hypertension syndrome.

Animals↗
PubMed1987

Red blood cell volume of the pig fetus.

A non-radioactive fluorescent excitation analysis technique was used to measure total red blood cell volume in 31 unanaesthetised pig fetuses in utero. Red blood cell volume (y in ml) was closely related (r = 0.94) to fetal bodyweight (x in g): where y = 2.92 + 0.0291x. Average red blood cell volume was 34 +/- 1 ml kg-1 fetal bodyweight. Average estimated (total) blood volume was 117 +/- 3 ml kg-1 fetal bodyweight. It was concluded that this non-radioactive indicator dilution measurement of red blood cell volume is a significant advance over the established 51Cr method, and that measurement of red blood cell volume may be used to estimate fetal bodyweight in utero.

Animals↗
PubMed1986

Increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs.

Mechanically induced hyperventilation is used in the treatment of newborn infants with persistent pulmonary hypertension syndrome to induce respiratory alkalosis, which may attenuate their pulmonary vasoconstriction. Whether this treatment is effective because of the increase in arterial pH or the decrease in Paco2 was investigated in nine sedated, mechanically ventilated newborn lambs with hypoxia-induced pulmonary vasoconstriction. We found that respiratory alkalosis and metabolic alkalosis were equally effective in attenuating hypoxia-induced pulmonary vasoconstriction, but that hypocapnia (low Paco2 with a normal arterial pH) was ineffective. These results indicate that increased arterial pH, not decreased Paco2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs and possibly the pulmonary vasoconstriction in newborn infants with persistent pulmonary hypertension syndrome.

Alkalosis↗
PubMed1986

Cardiovascular effects of d-tubocurarine and pancuronium in newborn lambs during normoxia and hypoxia.

Nondepolarizing muscle relaxants are administered to hypoxic neonates (including those with severe cyanotic congenital heart disease) to reduce oxygen consumption. However, it is unknown whether paralysis actually reduces oxygen consumption or whether the drugs used affect the cardiovascular system of neonates. Therefore, we studied the effects of d-tubocurarine and pancuronium induced muscle paralysis on oxygen consumption, cardiac output, and tissue oxygen delivery in healthy normoxic and hypoxic 1- to 3-day-old lambs. We measured intravascular pressures, cardiac output and its distribution (microspheres), and blood gases and pH during: 1) spontaneous respiration with room air (control); 2) spontaneous respiration with a Pao2 of 27-33 mm Hg (hypoxia); 3) mechanical ventilation with room air; 4) mechanical ventilation with room air and paralysis with d-tubocurarine (0.3 mg/kg) or pancuronium (0.1 mg/kg); and 5) mechanical ventilation with hypoxia and paralysis. Mechanical ventilation, with or without muscle paralysis, had no effect on the oxygen delivery or oxygen consumption of normoxic animals. Hypoxia and spontaneous ventilation had no effect on oxygen consumption, but hypoxia, paralysis, and mechanical ventilation reduced it 35% (p less than 0.002 d-tubocurarine) and 50% (p less than 0.001 pancuronium). Cardiac output was unaffected by oxygenation, mechanical ventilation, or muscle paralysis. However, blood flow to the brain and heart increased during hypoxia, which maintained normal oxygen delivery to these organs. During hypoxia and spontaneous ventilation, mean pulmonary arterial pressures increased 34% (d-tubocurarine) and 54% (pancuronium) above control; during hypoxia, muscle paralysis, and mechanical ventilation, it increased 81%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Non-narcotic analgesics. Use in pregnancy and fetal and perinatal effects.

Aspirin and related non-narcotic analgesics such as paracetamol (acetaminophen) are present in almost every 'Western' household and are so commonly used that the public often does not think of them as drugs. Although the toxic effects of overdoses are well recognised by the medical and related professions, the potential adverse effects of repetitive dosing, within the commonly recommended therapeutic range, are not. This is particularly true during pregnancy, where the relative overall general safety of the agents is overshadowed by the possible subtle but potentially pervasive effects on the fetus. Marketing publicity, particularly about recently introduced related agents, has at times failed to take into account these less obvious, but nevertheless potentially lethal, side effects. It is now likely that aspirin and/or paracetamol are used during pregnancy by most women and that the earlier figures are underestimates. Although animal studies have shown significant effects of non-steroidal anti-inflammatory agents (NSAIDs) on the fetal circulation, particularly on the developing pulmonary circulation, the data on human pregnancy are less convincing. Nevertheless, the possible association of these drugs with prolonged gestation, and an increased incidence of the syndrome of persistent pulmonary hypertension of the newborn and of intracranial haemorrhage, demand that prudence be exercised when using these drugs during pregnancy. At the very least, more conclusive evidence is necessary that fetal and neonatal complications are not increased.

Abnormalities, Drug-Induced↗