Autonomic control of cardiovascular functions during neonatal development and in adult sheep.

Abstract

SUMMARY We studied the autonomic control of resting heart rate and of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptormediated bradycardia, and acetylcholine-induced systemic hypotension is accompanied by a "paradoxical" tachycardia mediated through /3-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.PREVIOUS studies on fetal lambs between 60 days and term gestation (fetal weight, 300-5,00,0 g) have shown that (1) the sympathetic control of the cardiovascular functions begins earlier during fetal development than the parasympathetic control; (2) the influence of both systems on the fetal circulation increases with fetal growth until term; and (3) the fetal cardiovascular response to autonomic agonists increases during intrauterine development mainly because of maturation of the effector system. 1 ' 2The present report deals with data that compare the changes in the neurohumoral control of the heart rate, systemic arterial pressure, and pulmonary vascular pressure of the neonatal lamb (3-60 days of age) with changes in the adult nonpregnant sheep. MethodsNear-term ewes of mixed breed with well dated gestation were allowed to deliver spontaneously in our animal facilities; hence, the exact age of each lamb was known. The lambs were housed with their mothers so that normal lactation could be accomplished until they were able to eat the same alfalfa diet given to the ewes and drink on their own during the period of observation. Each lamb was allowed a 2-to 3-day period of neonatal adjustment before it was subjected to surgery. Chronic instrumentation of the lamb or the adult sheep was accomplished under a...

Differential Responses to Systemic and Local Angiotensin II Infusions in Conscious Postnatal Sheep

“…In the present study, basal MAP 1 wk postnatal was almost twice that reported in fetal sheep (1,7,9,31), and values continued to rise until after the second week postnatal. This pattern is consistent with other studies in neonatal sheep (38,39) and more recent data in preterm neonates (40). This secondary rise in MAP is not well studied and could reflect several mechanisms, including decreases in circulating levels of fetally derived vasodilators, increases in PVR due to enhanced vascular reactivity or increased plasma levels of vasoconstrictors, and/or increases in cardiac output.…”

“…There also were parallel dose-dependent increases in FmVR, but, as with MAP, responses were unchanged with age. This suggests that vascular reactivity is unchanged during the study period, which is consistent with earlier reports (29,38), or that vascular sensitivity increases; however, potential increases in the clearance and/or distribution of ANG II in the first month postnatal may result in similar pressor responses at all ages. Thus, Wilson et al (29) suggested that one had to use the plasma level of ANG II rather than the dose infused to evaluate age-dependent changes in newborn sheep, implying that ANG II clearance increases during the postnatal period and is agedependent.…”

“…If the rise in MAP is due to gradual increases in PVR (2,44,45), one would expect an increase in peripheral vascular reactivity, sympathetic tone, and/or circulating levels of agents such as ANG II. However, existing data do not support any of these as occurring after birth (29,38,46). For example, plasma ANG II falls in the human neonate as MAP rises, demonstrating an intact pressormediated negative feedback mechanism (46).…”

“…As noted above, as basal MAP rose with increasing postnatal age there was a parallel fall in resting HR. This reciprocal relationship between MAP and HR generally suggests either a resetting of the baroreceptor response (4) or a change in parasympathetic activity, which is reported to increase after birth (38,48). Although the level of parasympathetic activity can alter neonatal HR, the balance with sympathetic or adrenergic activity is not related to postnatal age (38).…”

Regulation of Cardiac Output with Controlled Heart Rate in Newborn Lambs

“…Considerable controversy has been raised regarding the potential effectiveness of P-adrenoreceptor agents in increasing myocardial performance during the newborn period (7,10,(29)(30)(31)(32). We have entertained the possibility that the main mechanism by which P-adrenergic agonists increased cardiac output in the neonate is through their effects in increasing heart rate rather than increasing contractility.…”