Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.
Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2–29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow.
The immediate transient baroreceptor sensitivity was measured in 9 conscious fetal and 7 conscious newborn lambs for periods of at least 35 days following bolus injections of phenylephrine (20–50 μg/kg). Mean sensitivities were unchanged throughout gestation from 105 days at 6.7 ± 0.4 msec/cm H2O (n = 45) and were insignificantly different from those in the newborn period, 5.9 ± 0.4 msec/cm H2O (n = 78). In contrast, baroreflex sensitivities were less in 2 fetuses and 2 newborn lambs when pressures were increased by chronically implanted thoracic aortic balloon cuffs; they were 3.03 ± 0.11 (n = 127) and 0.91 ± 0.11 msec/cm H2O (n = 61), respectively. ‘Steady-state’ heart period-arterial pressure curves indicate that the baroreflex operates down to levels of 40 cm H2O in the fetus which is lower than that achieved in the adult of other species, rabbit and man.
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