Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

Abstract

SummaryThe newborn beagle pup serves as a model for neonatal intraventricular hemorrhage (IVH). Fluctuations in germinal matrix blood flow are felt to play a major role in the pathogenesis of IVH. We studied regional cerebral blood flow in awake newborn beagle pups utilizing [14CI-iodoantipyrine as a blood flow indicator and quantitative autoradiography. The equilibrium [tissue]:[bloodl partition coefficient for iodoantipyrine was 1.13 + .06 for grey matter.Blood flow was calculated for cerebral cortex (frontal = 59 + 9 m1/100 &in), 14 subcortical nuclear structures (e.g., caudate = 45 + 6 m1/100 g/min), 3 white matter structures (centrum semiovale = 7 + 1 m1/100 g/min), and germinal matrix (7 + 1 m1/100 g/ min) (mean + S.E.).We conclude that under normal physiologic conditions the germinal matrix receives relatively low blood flow. This information can be used for comparison with germinal matrix blood flow during adverse experimental conditions. Speculation wLow baseline blood flow may place the germinal matrix at risk for ischemic injury during hypoxic or hypotensive stress. This ischemic injury may be a critical step in the pathogenesis of intraventricular hemorrhage, either by disrupting vascular integrity or by producing a disproportionate increase in germinal matrix blood flow (luxury perfusion) after reestablishment of normoxemia and normotension.Increasing attention is being focused on the regulation of cerebral blood flow (CBF) in newborn infants. The pathophysiology of both perinatal asphyxia and neonatal intraventricular hemorrhage have been linked to fluctuations in CBF (25). Although quantitative studies of CBF in newborn infants have been performed (22,24,29, 35), these results are limited by the poor spatial resolution of the techniques. Recent advances have made it possible to accurately measure blood flow to small brain regions in unanesthetized animals (1 8,19,30). We set out to study the regulation of regional blood flow (rCBF) in newborn animals. We utilized the beagle puppy as our experimental animal because the newborn beagle has recently been established as an animal model for neonatal intraventricular hemorrhage (8,9). In this report, we present in detail our methods and rCBF values for normal, unanesthetized pups. MATERIALS AND METHODSRegional cerebral blood flow (rCBF) was studied in newborn (12-48 h old) purebred beagle pups (Laboratory Research Enterprises, Inc., Kalamazoo, MI) by the methods of Sakurada et al.(30). The pups were lightly anesthetized with nitrous oxide and halothane. Polyethylene catheters filled with 1.0 international units (IU) Na heparin per 1.0 cc 0.9% NaCl were inserted bilaterally into the femoral arteries and veins via skin incisions. The wounds were infiltrated with 2% lidocaine jelly (Astra Pharmaceutical Products, Worcester, MA) and the hind quarters of the animal wrapped in a cotton stocking and fast-setting plaster bandage (Johnson and Johnson Co, New Brunswick, NJ). The plaster cast was secured to a lead brick. The animals were able to move their head and...

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

“…3). This contrasts with results of previous studies which showed no increase in white matter flow during hypoxia, in either the exteriorized fetal lamb or in the newborn puppy (6,30,32). These latter findings have been used to support the neuropathological observation of periventricular leukomalacia in infants who have suffered asphyxia1 brain injury.…”

Autoregulation of Cerebral Blood Flow in the Newborn Beagle Puppy

“…Moreover, careful evaluation o f two GM regions (GMMC and GMRC) reveals the following interesting characteristics: although baseline GMMC and GMRC blood flow is low and similar to blood flow in deep white matter regions, the blood pressure increment during hypertension is higher than deep white mat ter and similar to that seen in some grey mat ter structures. Thus, even though the GM is a 'low flow structure' under baseline condi tions [17], hypertension enhances GMMC and GMRC flow disproportionately when compared with deep white matter. Studies in littermate puppies (less than 24 h old) have shown that the GM capillaries have larger lumens, thinner walls, and are less well sup ported by perivascular stroma than capillar ies in cerebral cortex or caudate [22], Capil laries in cerebral white matter have prop erties intermediate between GM and grey matter.…”

“…Our methods have been extensively described in previous publications, and the details will not be repeated here [17,18,20], In brief, we measured regional cerebral blood flow (RCBF) in 17 puppies (12-60 h of age, 220-320 g). RCBF results from some of these puppies were previously reported [18].…”

Intraventricular Hemorrhage in the Newborn Beagle Puppy

“…Pasternak et al [16] provided evidence that the germinal matrix is, in addition, a low flow structure and may be particularly vulnerable to hypoxia and tis sue injury. Volpe [17] has suggested that hypoxia is the pivotal event that leads to circulatory failure, injury to the vascular endothelium, cerebral venous congestion, and, finally, IVH.…”