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Biomedical subjects

M A Heymann

Publications and source records attributed to M A Heymann.

At least 163 records · Page 9Linked to original sources
PubMed1976

Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis.

Inhibition of prostaglandin synthesis constricts the ductus arteriosus in fetal lambs in utero. We administered the inhibitors, aspirin or indomethacin to 18 premature infants with patent ductus arteriosus, and assessed the effects clinically and by echocardiography (left atrial/aortic-root ratio). After aspirin (20 mg per kilogram, every six hours for four doses) the ductus closed permanently in one infant within 24 hours; in another, constriction occurred with clinical improvement, and the third did not respond. In five infants given 0.3 mg per kilogram of indomethacin, complete closure occurred within one day; two of them, who received three doses had an elevated serum creatinine for one week. In one infant the ductus reopened, requiring a second dose of indomethacin 11 days after the first. Ten infants received 0.1 mg per kilogram of indomethacin, and closure occurred within 24 to 30 hours in eight. One had a soft murmur for four days, and one did not respond to two doses of indomethacin. A murmur reappeared after three to seven days in three infants but only one required further treatment. In infants receiving a single dose of 0.3 mg per kilogram, or one or more doses of 0.1 mg per kilogram, renal function was unaltered.

Aspirin↗
PubMed1976

Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output.

Right and left ventricular outputs were measured continuously in fetal lambs in utero for 2 to 21 days after implantation of electromagnetic flow tranducers around the main pulmonary trunk and ascending aorta. Surface pacing electrodes were implanted on the left and right atria. The intact cervical vagus nerve was stimulated by electrodes implanted around the nerve. Spontaneous increased in fetal heart rate were associated with increases in both right and left ventricular outputs and spontaneous falls in heart rate with reduction in both outputs. There was a linear relationship between fetal heart rate and ventricular outputs. Vagal stimulation reduced fetal heart rate with a consistent and linear fall in ventricular output. Left atrial pacing increased right ventricular output by 15 to 20 per cent but produced a variable response, ususally a fall, in left ventricular output. Right atrial pacing resulted in increases in both outputs but the increase in right ventricular output was less than during left atrial pacing at the same rate. The difference in response of ventricular outputs to induced as compared to spontaneous heart rate changes relates to the effects on left and right atrial phasic pressure relationships. These changes probably alter blood flow patterns across the foramen ovale.

Animals↗
PubMed1976

Persistent pulmonary hypertension of the newborn infant.

Persistent pulmonary hypertension of the newborn infant can be difficult to distinguish from other cardiopulmonary causes of cyanosis during the newborn period. Infants with PPHN have cyanosis, tachypnea, acidemia, normal pulmonary parenchymal markings on the chest radiography, and anatomically normal hearts. We have identified and treated 11 infants and have noted several signs and symptoms not previously emphasized. These are cineangiocardiographic evidence of atrioventricular valve insufficiency in association with systolic murmurs and slow ventricular emptying, apnea, hypocalcemia, only a small rise in abdominal aortic blood oxygen tension during breathing of 100% oxygen, and no response to continuous positive airway pressure. Right-to-left shunting through the patent ductus arteriosus was documented in nine infants: in all six of those in whom simultaneous temporal and abdominal aortic blood oxygen tension measurements were made; in three by means of cardiac catheterization. Ten infants survived after variable courses and treatments which makes it difficult to ascribe improvement to any one therapy. The distinct increase in blood oxygen tension with tolazoline HCl and curare in some instances is discussed.

Cyanosis↗
PubMed1976

Gestational differences in lidocaine toxicity in the fetal lamb.

Effects of lidocaine on arterial pressure, heart rate and electrocortical activity were studied in nine fetal lambs at 0.77 to 0.92 gestation (116 to 138 days of gestation; term in sheep is 150 days). Lidocaine was administered into a fetal femoral vein either as a continuous infusion or as a bolus injection. Epileptiform activity was observed in all fetuses both after continuous infusion and after bolus injection of lidocaine. Fetal arterial concentrations of lidocaine at the time of the first epileptiform discharge during continuous infusion ranged from 6.9 to 40.0 mug/ml, and correlated negatively with gestational age (Y equals -1.727 x +242.7; r equals -0.94). The increases in fetal mean arterial pressure during epileptiform bursts correlated directly with the gestational age (Y equals 1.27 x -150.0; r equals 0.91). The convulsive doses of lidocaine injected as a bolus ranged from 8.0 to 34.1 mg/kg, and correlated negatively with gestational age (Y equals -0.991 x +144.9; r equals -0.88). The increased sensitivity to lidocaine of the fetal central nervous system with advancing gestation probably reflects differences in fetal brain development. The increase in cardiovascular responses to epileptiform activity with advancing gestation could be related to differences either in the strength of epileptiform discharges or in permeability of the blood-brain barrier to lidocaine, or to immaturity of the autonomic nervous supply to the cardiovascular system in young fetuses.

Animals↗
PubMed1976

Morphological development of the pulmonary vascular bed in fetal lambs.

The morphological development that accompanies increasing pulmonary blood flow and decreasing pulmonary vascular resistance with advancing gestational age has not been delineated. To study this point we developed a method of comparing pulmonary arterial vessels of the same generations in fetal lambs. Pulmonary arteries were perfused with glutaraldehyde solution at pressures appropriate for gestational age and then injected with an India ink-gelatin-Micropaque mixture. Using the dissecting microscope and serially prepared sections we studied successively smaller generations of arteries. We assessed the medial width/external diameter ratio in a total of 825 vessels from six fetal lambs of 85 to 140 days gestation. In fifth generation, or resistance vessels, this ratio remained constant over the gestational period studied (N = 529, Y = 0.16, slope = 0.0003). We measured the volume of 17-34 randomly selected sections from each of the six fetuses, counted the total number of fifth and sixth generation vessels in these sections, and calculated the total number of these vessels per right lung. This number increased from 0.10 X 10(6) to 4.08 X 10(6) with increasing gestational age. The number of vessels per unit volume increased from 7.2 X 10(3)/ml to 61.8 X 10(3)/ml or right lung over this gestational period. The results indicate that increased pulmonary blood flow and decreased pulmonary vascular resistance with advancing gestation are due to an increase in the total number of vessels and increased vasomotor reactivity is related to an increase in the total amount of smooth muscle while the thickness of muscle in individual vessels remains constant.

Animals↗
PubMed1976

Relationships between pressure and flow in the umbilical and uterine circulations of the sheep.

We studied the relationship of fetal and maternal vascular pressures to umbilical and uterine blood flow in the unanesthetized ewe and in the sheep fetus in utero by placing electromagnetic flow transducers around both the common umbilical and uterine arteries. Reductions in umbilical arterial pressure or elevations in umbilical venous pressure decreased umbilical blood flow without affecting either the uterine arterial blood flow or other maternal cardiovascular variables which were studied. Elevations in uterine venous pressure or reductions in uterine arterial pressure decreased uterine arterial flow but these interventions had no effect on umbilical blood flow until fetal hypoxemia and bradycardia occurred. When the bradycardia of the fetal hypoxic response was inhibited by atropine, alterations in maternal vascular pressure had no effect on umbilical arterial flow. These data do not support the presence of a "sluice" or "waterfall" effect in the umbilical-placental circulation of the sheep fetus in utero.

Animals↗
PubMed1976

Effects of acetylsalicylic acid on the ductus arteriosus and circulation in fetal lambs in utero.

Intra-arterial and intravenous catheters were inserted in six fetal lambs at 125-130 days of gestation. On the following day, fetal arterial pressures and blood gases were monitored and fetal cardiac output and its distribution were measured by injection of radionuclide-labeled microspheres 15 mum in diameter. Acetylsalicylic acid, 55-90 mg/kg of estimated fetal weight, then was administered into the fetal stomach. Fetal pulmonary arterial pressure rose significantly after an average of 58 minutes, increasing the pressure difference between the pulmonary artery and the aorta from 2 +/- 0.3 (SEM) mm Hg during control to 11.2 +/- 1.6 mm Hg. Resistance across the ductus arteriosus rose from 4.2 +/- 0.5 (SEM) to 27.4 +/- 4.01 units, and flow fell from 495 +/- 44 (SEM) to 409 +/- 20 ml/minute. The proportion of combined ventricular output distributed to the placenta, adrenals, heart, and lungs increased, whereas the proportion of combined ventricular output distributed to the brain, liver, intestine, kidneys, and upper and lower body fell. In two fetuses infusion of prostaglandin E1 reversed the pulmonary hypertension. Inhibition of prostaglandin synthesis in fetal lambs produced constriction of the ductus arteriosus and redistribution of cardiac output. It is probable that prostaglandins, particularly E1, are involved in regulation of blood flow through the ductus arteriosus and various vascular beds in the normal resting fetus.

Animals↗
PubMed1976

Gestational changes in pulmonary vascular responses in fetal lambs in utero.

Pulmonary arterial (PA) blood flow patterns, changes in pulmonary blood flow, and pulmonary vascular responses to graded hypoxemia and intravenous acetylcholine (ACh) were studied in 15 fetal lambs in utero 3-12 days after surgical implantation of an electromagnetic flow transducer and PA catheter. Phasic PA flow in the fetus was forward only during the first third of systole, almost zero during midsystole, and backward during late systole and early diastole. In contrast, neonatal lambs showed forward PA flow throughout systole. The constriction of the fetal pulmonary vasculature in response to progressive hypoxemia varied with gestational age. At 103 days there was no significant drop in PA flow and only a small increase in pulmonary vascular resistance (Rp) with hypoxemia. The greatest increase in Rp was seen in fetuses after 121 days of gestation. This response was unaffected by alpha- and beta-sympathetic and parasympathetic blockade. Similarly, the pulmonary vascular response to ACh injected into the fetal jugular vein depended on gestational age. Little or no increase in pulmonary flow was noted in the youngest fetus, whereas ACh produced a marked increase in pulmonary flow in festuses over 120 days of gestation. These data suggest that the mechanisms by which hypoxemia constricts and ACh relaxes the pulmonary vascular smooth muscle are not fully developed in fetal lambs at 100 days of gestation and furthermore, that these mechanisms progressively develop during the last third of gestation.

Acetylcholine↗
PubMed1976

Cardiovascular effects of electrical stimulation of the forebrain in the fetal lamb.

Modified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115-135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of alpha-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to beta-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation.

Adrenergic beta-Antagonists↗
PubMed1975

Transfer of lidocaine across the sheep placenta to the fetus. Hemodynamic and acid-base responses of the fetal lamb.

Placental transfer of lidocaine administered to pregnant sheep and removal of the drug from the fetal circulation were determined. Responses of the hemodynamic and acid-base state in the mother and fetus were also studied. Lidocaine readily crossed the placenta and appeared in the fetal blood as early as one minute following injection. Disappearance of lidocaine in the asphyxiated fetus tended to be slower than in the normal one. Lidocaine produced a transient fall in the fetal heart rate which was accompanied by a decrease in blood pH and oxygenation. Lidocaine also reduced umbilical blood flow and, in some instances, uterine blood flow. Decrease in umbilical blood flow was more pronounced in the initially asphyxiated fetus.

Acid-Base Equilibrium↗
PubMed1975

Formalin infiltration of the ductus arteriosus. A method for palliation of infants with selected congenital cardiac lesions.

To circumvent the decreased pulmonary blood flow associated with closure of the ductus arteriosus in newborns with heart defects, we infiltrated buffered formalin solution into the wall of that structure to delay its closure. In four infants with pulmonary atresia in whom shunts had been unsuccessful or were technically not feasible, this procedure produced rapid improvement of arterial oxygen tension that was maintained in three infants for one to nine months. The other died of complications of attempted shunt procedures. In an infant with interrupted aortic arch and a large ventricular septal defect, formalin infiltration of the ductus and pulmonary arterial banding alleviated cardiac failure and improved lower-body perfusion. Formalin infiltration of the ductus is an effective palliative technic for treating certain congenital cardiac defects. No adverse effects have been noted.

Aorta↗
PubMed1975

Measurement of umbilical blood flow in fetal lambs in utero.

We continuously measured umbilical blood flow in fetal lambs in utero by placing an electromagnetic flow transducer around the common umbilical artery. Umbilical arteries originate from a short common segment as the terminal branches of the descending aorta. This segment was isolated by a retroperitoneal surgical approach and encircled with a specially constructed electromagnetic flow transducer. Catheters were also placed in fetal vessles to monitor pressure and derive flow values by the radionuclide-labeled microsphere technique. The fetus and ewe were allowed to recover for two days before studies were performed. Average umbilical blood flow obtained in 11 animals with the transducer was 199 ml/kg per min. In seven animals flow measurements obtained with the transducer were compared with those derived from microsphere injections. Paired measurements varied by an average of only 5.3%. This technique makes possible the accurate and instantaneous measurement of umbilical blood flow in fetal lambs in utero over a prolonged period.

Animals↗
PubMed1975

Control of the ductus arteriosus.

In the fetus the major function of the ductus arteriosus is to divert flow away from the lungs toward the placenta, therby avoiding unnecessary circulation through the lungs and reducing the work load of the heart. Constriction of the ductus arteriosus is produced by several mechanisms that may interact with one another in producing normal postnatal closure of the ductus arteriosus. The major mechanism is the constrictor effect of an increased O2 environment. This may directly affect the ductus arteriosus muscle or may work through the release of an intermediary substance. Other vasoactive substance circulating in the blood after birth may also play some role in constriction of the ductus arteriosus. There are major species differences in the degree and type of response to the various stimuli and the exact mechanisms ultimately responsible for closure are not yet fully understood.

Acetylcholine↗
PubMed1975

Early onset of pulmonary vascular obstruction in patients with aortopulmonary transposition and intact ventricular septum.

Of 29 patients with aortopulmonary transposition with intact ventricular septum who underwent cardiac catheterization as neonates, five subsequently developed increased pulmonary vascular resistance at an early age (7 months to 2 1 2 years). The resistance was high in two patients (11.0 and 12.9 units (U)/m-2), moderate in one (5.5 U/m-2) and mild in two (3.6 and 4.6 U/m-2). The two patients with the highest resistances died as a result of the pulmonary vascular obstruction and it was probably a contributing factor in the death of a third patient. The finding of pulmonary vascular obstruction at an early age in five of 29 patients with transposition of the great arteries with intact septa is noteworthy. It assumes even greater significance as the measurement methods tend to underestimate pulmonary vascular resistance. The possible errors in assessing pulmnary vascular resistance and factors possibly contributing to early development of pulmonary vascular obstruction are discussed.

Blood Pressure↗
PubMed1975

Congenital heart disease in low birth weight infants.

In this study of low birth weight infants (less than 2500 g), we compared the birth weight distribution of patients with patent ductus arteriosus associated with prematurity with that of patients having congenital heart disease other than patent ductus arteriosus. Among 1436 low birth weight infants 37 infants had congenital heart disease other than patent ductus arteriosus and 198 had isolated ductus arteriosus. Infants with congenital heart disease had a mean birth weight of 2018 grams (standard deviation = 370 g) which was significantly greater than that of infants with patent ductus arteriosus. Four of the 37 infants with congenital heart disease other than ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 3.5/1000 live low birth weight infants. Seventy-eight of the 198 infants with patent ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 70/1000 live low birth weight infants. Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age and 16 were small for gestational age.

Aorta↗