Regional Cerebral Blood Flow after Hemorrhagic Hypotension in the Preterm, Near-Term, and Newborn Lamb

Abstract

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.

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

“…Chronic instrumentation also allows a wide range of practical and clinically pertinent cerebral insults to be administered. These include global cephalic ischemia [65], systemic hypotension or hypoxemia [66][67][68], single or repeated cord occlusion [69][70][71], increased intracranial pressure [72], and administration of infectious agents or exogenous inflammatory mediators [73][74][75]. These insults can be graded in intensity and duration to mimic the human situation.…”

“…The sheep fetus displays cerebral hemodynamics similar to humans and permits repeated physiological measurements in utero in the unanesthetized state. Importantly, similar to the human fetus [77][78][79][80], the fetal sheep displays a very limited range of cerebral autoregulation under normal conditions and a pressure-passive cerebral circulation when subjected to systemic hypoxia and associated hypotension [66,[81][82][83][84]. Moreover, measurements of BP, electroencephalography, blood oxygenation, and other vital variables can be correlated with acute changes in cerebral blood flow and metabolism.…”

Pathogenesis of hypoxic-ischemic brain injury

“…The importance of impaired CBF autoregulation, even after modest asphyxia in the genesis of ischemic cerebral injury is supported by animal and experimental studies. 14,22 The implications are enormous, namely a decrease in blood pressure will result in a decrease in CBF, thus markedly increasing the vulnerability for neuronal injury, particularly within the border zone regions of the brain such as parasagittal cortex or periventricular white matter. 14 …”

The Ontogeny of Cerebrovascular Pressure Autoregulation in Premature Infants

“…The mammalian cerebral vasculature develops muscularity at approximately two-thirds gestation, which corresponds to 26-27 weeks' gestation in humans, so extremely premature infants may lack the necessary arteriolar tone needed to impart pressure autoregulation. 23,24 The ontogeny of autoregulation is therefore germane to our interpretation of pressurepassivity in premature infants.…”