The Effects of Clinical Concentrations of Halothane on the Blood Flow and Oxygen Uptake of the Cerebral Cortex

The effect of the calcium antagonist nimodipine on local CBF in 31 regions of the CNS was studied with the [14C]iodoantipyrine autoradiographic technique in lightly anaesthetised, mechanically ventilated rats. Continuous intravenous infusion of nimodipine (1, 2, or 4 μg kg−1 min−1) produced a dose-dependent reduction in MABP (reduced by 26 ± 2% after 30 min of nimodipine, 4 μg kg−1 min−1) and a significant elevation in plasma glucose concentration (increased by 44 ± 2% after 30 min of nimodipine, 4 μg kg−1 min−1). Local CBF was increased significantly during infusions of nimodipine (1 μg kg−1 min−1) in 9 of the 31 regions examined (including the cerebral cortex, hippocampus, hypothalamus, and most thalamic nuclei). In contrast to the increases in CBF observed in forebrain regions, no significant increases in CBF were observed during nimodipine infusions in regions of the lower brainstem, cerebellum, and pons or in myelinated fibre tracts. The proportionately greatest increases in local CBF were observed during infusions of the lowest dosage of nimodipine (1 μg kg−1 min−1), suggesting either that this dosage provokes maximum cerebrovascular relaxation or that effects of increasing concentrations are counteracted by the concomitant systemic hypotension.

Section: General Surgery and Animal Preparationmentioning

confidence: 95%

Effect of the Calcium Antagonist Nimodipine on Local Cerebral Blood Flow: Relationship to Arterial Blood Pressure

Mohamed

McCulloch

Mendelow

et al. 1984

“…There is a considerable literature documenting the acute vasomotor effects of halothane and other anesthetics in specific vascular beds, but interactions between focal ischemia and anesthesia withdrawal have not been extensively examined, much less in the context of repeated anesthesia. Halothane and related anesthetics increase CBF (Farber et al, 1997;Hansen et al, 1988;Jensen et al, 1992;Koenig et al, 1993;McDowall, 1967). Spontaneously hypertensive rats and Wistar-Kyoto strains exhibit particularly prominent perfusion increases during halothane exposure with metabolic suppression by pentobarbital (Takahashi et al, 1996).…”

Section: Sham Effects and The Contribution Of Anesthetic Preconditioningmentioning

confidence: 99%

CBF Changes Associated with Focal Ischemic Preconditioning in the Spontaneously Hypertensive Rat

Zhao

Nowak

2006

Experimental stroke models exhibit robust protection after prior preconditioning (PC) insults. This study comprehensively examined cerebral blood flow (CBF) responses to permanent middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats preconditioned by noninjurious transient focal ischemia, using [ 14 C]iodoantipyrine autoradiography at varied occlusion intervals. Preconditioning was produced by 10-min occlusion of the MCA and ipsilateral common carotid artery under halothane anesthesia. These vessels were permanently coagulated 24 h later in naïve, PC, and sham-operated rats. Infarct volumes were determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days. Edema-corrected infarct volume was reduced from 127621 in naïve rats to 101631 and 52628 mm 3 in sham and PC groups, respectively, at 1 day, with similar results at 3 days. All animals exhibited a consistent CBF threshold for infarction (approximately 30 mL/100 g/ min). Tissue volumes below this threshold were identical in naïve and PC groups after 15-min occlusion. However, by 3 h the volume of ischemic cortex decreased in the PC group but remained unchanged in naïve rats, predicting final infarct volumes. Cerebral blood flow recovery was confirmed in brains of individual rats evaluated by repeated laser Doppler perfusion imaging during the same 3-h interval. Modest sham protection correlated with better-maintained global perfusion, detectable also in the contralateral cortex, apparently reflecting the PC effects of prior anesthesia. These results establish that timely reperfusion of penumbra, achieved by synergistic mechanisms, is a primary determinant of PC-induced protection in experimental stroke.

“…These reports, however, may not apply to awake animals because general anesthesia may have sig nificantly contributed to the CBF increases (Kanda and Flaim, 1986), perhaps by opening the blood brain barrier to nimodipine (Harper et aI., 1981;Scriabine et aI., 1985). Anesthesia (e.g., halothane) can also cause hypotension (Keaney et aI., 1973), induce respiratory acidosis (if the animal is not me chanically ventilated), disturb cerebral autoregula tion (Forster et aI., 1978;Hickey et aI., 1988), open the blood-brain barrier (Forster et aI., 1978), de press cerebral O2 consumption (Morita et aI., 1977) and energy metabolism (Michenfelder and Theye, 1975), and increase CBF in both ischemic and nonischemic structures (McDowall, 1967;Smith et aI., 1973;Anderson et aI., 1980). These side-effects of anesthesia can seriously complicate the interpre tation and clinical relevance of experimental stroke studies, especially when evaluating drug therapy.…”

Section: --mentioning

confidence: 99%

Continuous Nimodipine Treatment Attenuates Cortical Infarction in Rats Subjected to 24 Hours of Focal Cerebral Ischemia

Jacewicz

Brint

Tanabe

et al. 1990

Summary: Focal cerebral infarction and edema were measured in rats (Wi star, Fisher 344, and spontaneously hypertensive strains) pretreated with nimodipine (2 I-Lg/kg/min i.v.) or its vehicle and subjected to the tandem occlusion of the middle cerebral and common carotid ar teries. Animals awoke from anesthesia 10--15 min after onset of ischemia and continued to receive treatment over a 24-h survival period. Cortical infarction and edema were quantified by image analysis of frozen brain sections processed for histology. Nimodipine-treated rats devel oped 20--60% smaller cortical infarct volumes than conThere is growing evidence that pretreatment with nimodipine, a calcium channel blocker and potent cerebral vasodilator, can protect against focal cere bral ischemic damage. If administered before the experimental induction of focal cerebral ischemia, nimodipine has been shown to increase residual CBF in the ischemic bed, ameliorate local acidosis (Meyer et aI., 1988), and reduce the extent of his tologic damage (Mohamed et aI., 1985a) measured 4 h after onset of ischemia. Clinically, the number of ischemic strokes complicating aneurysmal sub arachnoid hemorrhage has been consistently re duced by nimodipine pretreatment (Allen et aI.,