Arterial Oxygenation Determines Autoregulation of Cerebral Blood Flow in the Fetal Lamb

Abstract

Summary MATERIALS AND METHODSWe examined autoregulation of cerebral blood flow (CBF) over the range of oxygen tension commonly observed in the chronic fetal lamb preparation. Seventeen animals were surgically prepared under general anesthesia for chronic in utero studies. ~a s e d on measured resting arterial Po2 and calculated % saturation 24-48 h after surgery, two groups were defined: a normoxic group of eight with saturation of 57% or higher (our laboratory normal for physiologically stable preparations) and an hypoxic group of nine with saturation less than 57%. Regional CBF was measured with radiolabeled 15-pm microspheres. Autoregulation of CBF was assessed by measuring the change in CBF when fetal mean arterial blood pressure (MABP) was acutely decreased and increased by withdrawal and reinfusion of fetal blood. In normoxic animals CBF was constant over an MABP range of 42-61 torr in all four areas of the brain examined: cerebral hemispheres, basal ganglia, cerebellum, and brain stem. In hypoxic animals CBF was pressure dependent in all areas over an MABP range of 46-73 torr, i.e., autoregulation was abolished. These studies demonstrate that the mechanism of autoregulation is functionally developed in the mature fetal lamb, but operationally dependent upon arterial oxygen concentration. Below a saturation of approximately 50-60% CBF varies directly with perfusion pressure. AbbreviationsBP, blood pressure CBF, cerebral blood flow cpm, count per min i.d., internai diameter MABP, mean arterial blood pressure rCBF, regional cerebral blood flow Impairment of cerebrovascular autoregulation is now generally believed to be an important pathophysiologic mechanism in the genesis of hypoxic and hemorrhagic brain injury of the newborn (10, 20). The theoretical model states that with impairment of autoregulation the cerebral microcirculation is rendered vulnerable to changes in arterial blood pressure. Systemic hypotension results in ischemic cerebral blood flow (CBF) and cerebral infarction, whereas hypertension leads to cerebral hyperemia, rupture of poorly supported capillaries in the vulnerable subependymal germinal matrix, and cerebral hemorrhage (10, 15).Impaired autoregulation has been demonstrated in the severely asphyxiated fetal lamb (12) and in sick human newborns (1 1). The well oxygenated newborn lamp has been shown to autoregulate (16), and there is evidence that the normoxic fetal lamb has at least partial autoregulatory control of CBF (19). But the functional maturity of the autoregulatory mechanism in the fetal lamb, and its sensitivity to hypoxia, have not been clearly established.The present studies were designed to examine autoregulation in utero in the near term fetal lamb, and to determine its stability over the range of arterial oxygen tension normally encountered in chronically prepared laboratory animals.We studied 17 near term fetal lambs estimated to be 130-140 days gestation. Our methods for fetal studies in the chronically prepared sheep have been described in previous publications (12, ...

Regional Cerebral Blood Flow: Studies in the Fetal Lamb during Hypoxia, Hypercapnia, Addosis, and Hypotension

“…In fetal lambs, a 20% reduction in blood volume was accompanied with decreases in blood pressure of 21 %, in cardiac output of 40%, and in CBF of 18% when corrected for the 4-tom increase in Pco2 which occurred (39). In other studies, autoregulation was observed in normoxic fetal lambs as blood pressure ranged from 42 to 6 1 mm Hg (38). A 26% mean decrease in arterial blood pressure resulted in no significant change in total or regional brain blood flow (38).…”

“…In other studies, autoregulation was observed in normoxic fetal lambs as blood pressure ranged from 42 to 6 1 mm Hg (38). A 26% mean decrease in arterial blood pressure resulted in no significant change in total or regional brain blood flow (38).…”

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

“…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.…”

“…The importance of the central autonomic system and adrenal stress hormones remains unclear, as well as the systemic blood concentrations of metabolic substrates, such as glucose and products such as lactate. The fetal sheep brain, in particular when immature and hypoxemic, has essentially no ability to autoregulate [81][82][83]. Hence, in umbilical cord occlusion models, the fall in BP exacerbates the fetal brain hypoxia with a consequent reduction in CBF that leads to partial ischemia.…”

Fetal cerebrovascular response to chronic hypoxia—implications for the prevention of brain damage

“…Experiments on fetal lambs have shown that even acute, short-term hypoxia can affect cerebral autoregulation. Oxygen saturation at 50% lasting longer than 10 minutes has been shown in a global abolition of cerebrovascular autoregulation for several hours (35,36). Furthermore, impaired oxygen transfer across the placenta (e. g. in placental abruption) is one of the common causes of the loss of cerebral autoregulation in neonates, and autoregulation seems to be more vulnerable than other regulatory mechanisms for the cerebral circulation (37).…”