Anesthetic Choice of Halothane Versus Propofol

Abstract

Background and Purpose-It is not known whether preischemic exposure to anesthetic agents affects the amount of damage from transient focal ischemia that occurs after cessation of the anesthetic. We compared the effect of prior exposure to halothane or propofol on infarction size after transient middle cerebral artery occlusion (MCAO) induced in the awakening animal to test the hypothesis that anesthetic type and exposure duration would independently affect the amount of brain injury. Methods-Male Wistar rats (weight, 200 to 300 g) were anesthetized briefly with halothane for placement of hemodynamic instrumentation. Twenty-four hours later, rats were treated with either a short (approximately 1 hour) or long (8 hours) duration of inhaled halothane (1% to 2%) or intravenous propofol (10 mg/kg bolus, 30 mg/kg per hour infusion). Each cohort (nϭ8 per group) was then subjected to 2-hour MCAO by the intraluminal suture technique. All anesthesia was discontinued once MCAO was achieved. Infarct volume was measured at 22 hours of reperfusion. In a second cohort, regional cerebral blood flow (CBF) was measured ([ 14 C]iodoantipyrine autoradiography) at end-occlusion in shortduration halothane (nϭ5) or short-duration propofol (nϭ5) anesthesia groups and in corresponding surgical shams (nϭ3 each). Results-Pericranial temperature, PaO 2 , PaCO 2 , and blood pressure were controlled and not different among groups before or during occlusion. MCAO resulted in a similar immediate reduction in laser-Doppler flow signal after discontinuation of anesthesia in the awakening animals. Infarct volume was smaller in rats exposed to short-duration halothane in cortex (87.5Ϯ16.6 mm 3 ) (meanϮSEM) and caudoputamen (38.3Ϯ13.7 mm 3 ) compared with rats exposed to short-duration propofol (cortex, 177.5Ϯ16.9 mm 3 ; caudoputamen, 47.8Ϯ2.9 mm 3 ). Infarct volume was not different in long-duration halothane versus long-duration propofol treatment. Absolute cortical or caudoputamen intraischemic CBF was not different between short-duration halothane or short-duration propofol treatment.Conclusions-These data demonstrate that short-duration halothane exposure before MCAO in the awakening animal attenuates infarction volume compared with propofol. This protection by halothane is not mediated through preservation of intraischemic CBF. Longer durations of halothane exposure may activate secondary injury pathways, which negate the protective effects of short-term halothane preischemic treatment.

Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases

“…Because most anesthetics are neuroprotective when present during ischemia (Miura et al, 1998;Bhardwaj et al, 2001), we awakened rats immediately once the arterial occlusion was achieved to minimize the presence of anesthetics during ischemia and to maximally simulate clinical situation. Similar to the results reported before (Kapinya et al, 2002;Xiong et al, 2003), isoflurane preconditioning improved neurological outcome assessed within 4 days after the MCAO.…”

Inhalational Anesthetics as Neuroprotectants or Chemical Preconditioning Agents in Ischemic Brain

“…Kapinya et al (2002a) observed that in male rats, a 3 h pretreatment with 1.2% (1 MAC) halothane 24 h before permanent MCAO reduced infarct volume measured 4 days after initiation of ischemic injury. In a transient model of focal ischemia in male rats comparing the effects of immediate preischemic exposure of halothane and propofol, a 1 h exposure of 1% to 2% halothane attenuated infarction volume compared with propofol (10 mg/kg bolus, 30 mg/kg per hour infusion) whereas no differences in infarct size were seen between halothane and propofol treatment groups when the preischemic exposure period was extended to 8 h (Bhardwaj et al, 2001). Even fewer in vitro studies have been performed examining halothane preconditioning effects on neuronal injury.…”

Tolerance Against Ischemic Neuronal Injury Can Be Induced by Volatile Anesthetics and Is Inducible NO Synthase Dependent

“…[1][2][3][4][5] In a model of incomplete hemispheric ischemia, Baughman et al 1 demonstrated neuroprotection in rats anesthetized with isoflurane or halothane. Warner et al 2 demonstrated the neuroprotective effect of halothane or sevoflurane during focal cerebral ischemia in rats.…”

“…3 Miura et al 4 provided evidence that protection against neuronal injury by isoflurane during near-complete ischemia is superior to protective effects of fentanyl or ketamine anesthesia. In a recent publication, Bhardwaj et al 5 presented data on neuroprotection with halothane anesthesia after focal cerebral ischemia induced immediately after the termination of anesthesia. All these studies used volatile anesthetics shortly before and during the ischemic period.…”