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Biomedical subjects

H M Stein

Publications and source records attributed to H M Stein.

5 recordsLinked to original sources
PubMed1995

Effect of corticosteroids on free and sulfoconjugated catecholamines at birth in premature newborn sheep.

We previously demonstrated that prenatal corticosteroids attenuated the expected exponential increase in circulating catecholamines at birth. The present studies were undertaken to determine if alteration in sulfoconjugation could account for this attenuation. Catheterized fetal lambs received saline (n = 6) or corticosteroids (n = 8) intravenously for 60 h. The lambs were delivered by cesarean section at 130 +/- 1 days gestation. Ventilatory and cardiovascular responses and plasma catecholamine concentrations were measured for 2 h after birth. Although plasma free catecholamines levels were higher in controls than in corticosteroid-treated fetuses, the sulfoconjugated levels were similar in the two groups. Thus the corticosteroid-treated fetuses had a higher proportion of plasma sulfoconjugated catecholamines consistent with the possibility that sulfoconjugation was augmented during intrauterine life. After birth, the corticosteroid-treated animals showed an attenuated increase in plasma free catecholamine levels compared with controls but a similar increase in sulfoconjugated catecholamine levels to the control animals. The proportion of plasma sulfoconjugated catecholamines was higher in the corticosteroid-treated animals; however, the increase in sulfoconjugated catecholamines was insufficient to account for the attenuated overall increase in total catecholamines in the corticosteroid-treated animals.

Adrenal Cortex Hormones↗
PubMed1994

The effects of corticosteroids and thyrotropin-releasing hormone on newborn adaptation and sympathoadrenal mechanisms in preterm sheep.

OBJECTIVES: We examined the effect of prenatal corticosteroids and thyrotropin-releasing hormone on postnatal adaptation and sympathoadrenal function in preterm lambs. STUDY DESIGN: Catheterized fetal lambs received saline solution (n = 6), corticosteroids alone (n = 8), or corticosteroids plus thyrotropin-releasing hormone (n = 6) for 60 hours. The lambs were delivered by cesarean section at a gestational age of 130 +/- 1 days. Ventilatory, cardiovascular, and metabolic responses and plasma catecholamine concentrations were measured for 2 hours after birth. Statistical analysis was performed by use of independent t tests or analysis of variance. RESULTS: Ventilatory function and cardiac contractility were significantly improved in both corticosteroid and corticosteroid plus thyrotropin-releasing hormone animals. Lambs treated with corticosteroid plus thyrotropin-releasing hormone had significantly higher aortic pressure and left ventricular blood pressure than either of the other groups. The postnatal norepinephrine and epinephrine surge was blunted in response to corticosteroid and corticosteroid plus thyrotropin-releasing hormone treatment. There were no differences in metabolic responses among the three groups. CONCLUSIONS: In premature lambs prenatal exposure to corticosteroids and thyrotropin-releasing hormone improves postnatal cardiovascular adaptation more than corticosteroids alone.

Adaptation, Physiological↗
PubMed1993

Effects of corticosteroids in preterm sheep on adaptation and sympathoadrenal mechanisms at birth.

This study investigates the effects of prenatal corticosteroid administration on newborn sympathoadrenal mechanisms involved in postnatal adaptation. Randomly assigned preterm (122-125 days) fetal sheep were treated with hydrocortisone or saline for 60 h and delivered by cesarean section. We examined postnatal physiological adaptation, sympathoadrenal responses, cardiac beta-receptor density, and the receptor-cyclase system. We observed increased ventilatory, cardiovascular, and metabolic responses function in the corticosteroid-treated animals despite a marked attenuation in the anticipated surge of plasma catecholamine concentrations and a decrease in epinephrine secretion rate, which is normally seen at birth. Myocardial beta-adrenergic receptor density and affinity states were comparable in both groups. Basal and agonist-mediated adenylyl cyclase activity in myocardial tissue was increased in the corticosteroid-treated animals. We speculate that the increase in myocardial adenylyl cyclase activity may be accompanied by similar changes in other organ systems and that this could account for the augmentation in respiratory, cardiovascular, and metabolic responses in the corticosteroid-treated animals.

Acclimatization↗
PubMed1992

Prolonged beta-agonist infusion does not induce desensitization or down-regulation of beta-adrenergic receptors in newborn sheep.

In adult animals, prolonged beta-agonist exposure leads to down-regulation of beta-adrenergic receptors and desensitization. Prior evidence from our lab suggests that this may not occur in developing animals. To study this, we measured the response to graded epinephrine infusion [2.7, 5.5, 13.6, 27.3 mumol/(kg.min), (0.5, 1.0, 2.5, 5.0 micrograms/(kg.min)], myocardial beta-agonist receptor density, and components of the receptor-cyclase system in newborn lambs before (n = 6) and after (n = 5) 3 d of continuous isoproterenol administration (2 micrograms/kg/min). beta-Adrenergic receptors were measured by radioligand binding. Epinephrine dose-response curves were analyzed for the threshold and slope for changes in mean blood pressure, systolic blood pressure, and heart rate versus plasma epinephrine levels. Despite 3 d of continuous isoproterenol infusion, we observed no desensitization of the hemodynamic response to epinephrine. There was a reduction in receptor density when expressed per membrane protein [155.3 +/- 19.5 (controls) versus 73.2 +/- 3.8 fmol/mg protein (agonist exposed), p less than 0.05], but no alteration in receptor density when expressed per g cardiac wet weight [258.8 +/- 39.9 (controls) versus 406.8 +/- 74.0 fmol/g wet weight (agonist exposed)]. There was no alteration in agonist affinity or in adenylyl cyclase activity after adjustment for membrane protein recovery. Prolonged beta-agonist infusion in newborn lambs does not desensitize hemodynamic responses to infused epinephrine. We propose that receptor regulation in developing animals is fundamentally different than in adult animals.

Adrenergic beta-Agonists↗