Autoregulation of Cerebral Blood Flow in Experimental Focal Brain Ischemia

Abstract

Summary:The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood flow (CBF) in areas of focal cerebral ischemia was stud ied in 15 spontaneously hypertensive rats (SHRs) anes thetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flow me try during manipulation of SAP with I-norepinephrine (hyperten sion) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipUlations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of > 30% of preocclu sion values. In areas where ischemic CBF was <30% of It is controversial whether increasing systemic arterial pressure (SAP) can improve the neurologi cal outcome after acute stroke (Olsen, 1982;Yatsu, 1982;Grotta, 1987; Meyer et aI., 1987). Studies in experimental animals have shown that raising SAP to hypertensive levels after induction of cerebral ischemia can lessen brain damage (Safar et aI., 1976; Hayashi et aI., 1984; Aspey et aI., 1987; Drummond et aI., 1988). Clinical data showing im proved neurological outcome associated with hy pertension after stroke are anecdotal (Farhat and Schneider, 1967 327 preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was <15% of baseline (6% change in CBF with each 10% change in SAP). These findings dem onstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the sever ity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia. Key Words: Arterial blood pressure-Cerebral blood flow autoregula tion-Experimental focal cerebral ischemia. Van Dellen and Buchanan, 1977). PomerantzOn the other hand, there is experimental (Fenske et aI., 1975; Spatz et aI., 1976;Michenfelder and Milde, 1977; Bleyaert et aI., 1980; Kogure et aI., 1981) and clinical (Gottstein and Seel, 1977) evi dence for a worsening of outcome from increasing SAP above normal levels after cerebral ischemia. The enhanced formation of cerebral edema, intra cranial hypertension, cerebral hemorrhage, pulmo nary edema, and cardiac failure by arterial hyper tension might all contribute to this worsening. The potential benefit of increasing SAP during cerebral ischemia is based on the assumption that this measure will increase CBF in tissue where au toregulation has been lost (Meyer et aI., 1973a, b). Though it is generally accepted that autoregulation is lost in ischemic brain, little is known about the quantitative relationships among SAP, CBF auto regulation, and level of ischemia. Th...

Reduction in Focal Cerebral Ischemia by Agents Acting at Imidazole Receptors

“…Doubling of LCBF in the normal hemisphere by hypercapnia or hypertension for 1 h following MCA occlusion did not alter the distribu tion or size of the infarction produced by MCA oc clusion. While changes within the penumbra were not measured, it is probable that the flow changes would be enhanced, since autoregulation is partially impaired in that zone (Dirnagl and Pulsinelli, 1990). The failure of elevations of LCBF to modify the magnitude of the infarction is in accord with the conclusions of some (Fenske et aI., 1975;Bleyarert et aI., 1980) but not all (Hayashi et aI., 1984;Drum mond et aI., 1988) that elevating LCBF does not afford protection from focal ischemia.…”

“…To assess whether the protective actions of RIL or IDA might relate to increasing CBF in the terri tory of tissue salvage, a region in which others have shown LCBF is substantially reduced (Dirnagl and Pulsinelli, 1990) following occlusion of the MCA. LCBF was ele vated in groups of five rats by either hypercapnia or hypertension.…”

Reductions in Focal Ischemic Infarctions Elicited from Cerebellar Fastigial Nucleus Do Not Result from Elevations in Cerebral Blood Flow

“…The FN or RVL was stimulated for 1 h (1 s on-l s off; 0.5-ms pulse duration; 50 Hz at five times the stimulus current needed to elevate AP by 10 mm Hg; 70-100 f.LA) while maintaining AP within autoregulated range for rCBF in SHRs (80-175 mm Hg) (Dirnagl and Pulsinelli, 1990) by simultaneously withdrawing blood (Nakai et aI., 1982). Sham-treated controls were not stimulated.…”

Inhibition of Nitric Oxide Synthesis Increases Focal Ischemic Infarction in Rat

“…Immediately following MCA occlusion, agents were administered intravenously with AP maintained within the autoregulated range (Dirnagl and Pulsinelli, 1990), if necessary, by infusion of phenylephrine (PHE). After 1 h, the cranial wound was covered with Gelfoam (Upjohn) and closed with sutures.…”