Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat

Abstract

Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3-to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4 -3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7-22.8%). The CBF-CO 2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p ϭ 0.026. Over the range of SBP (6 -54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r ϭ 0.80). CBF pressure autoregulation and reactivity to CO 2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain. In very preterm infants, brain injury has been associated with impaired pressure autoregulation of CBF. Accordingly, periventricular hemorrhage may result from abrupt hyperperfusion whereas periventricular leukomalacia has been related to ischemia (1-9).Cerebral pressure autoregulation refers to vascular mechanisms whereby CBF is held within constant levels during variations in perfusion pressure. Perfusion is thus maintained over a range of pressures by appropriate alterations in the diameter of precapillary arterioles. However, the lower limit of autoregulation is reached when the vessels become fully dilated and, beyond that point, any further decrease in pressure results in proportional drops in CBF. Several conditions may affect the autoregulatory plateau and increased CBF as well as complete pressure passiveness secondary to vasodilatation is observed during hypercapnia, hypoglycaemia, hypoxia, and seizure (10 -13).Cerebral pressure autoregulation has been documented in several newborn animals such as piglets, lambs, and puppies (14 -19). Most of these animals have rather mature brains at birth, and to compare vascular physiology with that of a preterm infant, the newborn rat pup served as a model (20,21). Because we could not control ventilation in this immature animal, we evaluated the cerebrovascular response to hemorrhagic hypotension during normocapnia and carbon dioxide inhalation. The hypothesis was that pressure autoregulation operates normally in the healthy immature brain. METH...

Influence of hypercapnic vasodilation on cerebrovascular autoregulation and pial arteriolar bed resistance in piglets

“…Clinical studies of neonates, which used the static autoregulatory index, have concluded that hypercapnia impairs autoregulatory reactivity in these patients (13,18). Finally, laboratory studies of acute hypercapnia in the newborn piglet and rat and the adult cat also have reported that hypercapnia impairs autoregulation (19,21,25). Our findings that induction of acute hypercapnia can impair autoregulation are consistent with these previously reported studies.…”

Rapid Assessment of Cerebral Autoregulation by Near-Infrared Spectroscopy and a Single Dose of Phenylephrine

“…Other studies have also validated NIRSderived cerebral Hb signals during acute cerebral perfusion pressure manipulations with independent CBF measures such as CBF velocities (18,19), microspheres (20), or laser-Doppler flowmetry (21,22). All those studies support the hypothesis that Hb signals are reliable CBF surrogates during pressure maneuvers and may therefore allow assessment of dynamic AR.…”

Fluctuating Pressure-Passivity Is Common in the Cerebral Circulation of Sick Premature Infants

“…First, we used the NIRS HbD signal as a surrogate for CBF. This was based on the strong correlation between HbD and CBF in previous animal validation studies (9,23). It may be argued that in some instances, a change in HbD could reflect a change in oxygen extraction fraction.…”