Oxygen consumption and cardiac output increase after birth, and myocardial performance is nearly at peak levels; these changes do not occur in lambs thyroidectomized before birth. The objectives of this research proposal are 1) to examine the role of thyroid and adrenal cortical hormones acting prenatally, in influencing postnatal cardiovascular adaption and metabolic adjustments and 2) to assess the relative importance of heart rate and myocardial contractility in regulating cardiac output after birth. A major hypothesis to be considered is that the late prenatal rise in plasma cortisol or thyroid hormone concentrations alone, or in conjunction, increase either the number of Beta-adrenergic receptors, or their response to stimulation, thus facilitating the response of the myocardium and of brown fat to circulating catecholamines. Also it is suggested that these hormones may stimulate the postnatal use of free fatty acids as a primary energy source, rather than carbohydrates, which are exclusively utilized by the fetal myocardium. The effects of prenatal thyroidectomy and inhibition of cortisol secretion on cardiovascular function and oxygen consumption, and their response to Beta-adrenergic stimulation by isoproterenol, in fetal lambs and neonatal lambs, will be studied. B-adrenergic receptors will be examined directly quantitatively and qualitatively in heart muscle and brown fat in normal, thyroidectomized and cortisol-inhibited fetal and newborn lambs. It is conjectured that cardiac output is largely regulated by heart rate in the neonate and that the baroreflex is an important determinant of cardiac output. Cardiac output responses to various catecholamines will be studied while heart rate is maintained constant by pacing. These studies are potentially important in the postnatal cardiovascular and metabolic responses of infants delivered prematurely. If not subjected to the late gestational increase in hormone concentrations, the usual increase in cardiac output and oxygen consumption may be impaired. Prenatal hormone administration could influence these functions as well as lung maturation. An appreciation of the mechanisms regulating cardiac output after birth is extremely important in choice of therapeutic drugs for cardiorespiratory distress in the neonatal period.
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