The known cytoprotective properties of MgSO4 led the authors to study its effects on infarct size in rats when administered intraarterially before reversible focal ischemia. Following an intracarotid infusion of MgSO4 in the amount of 30 mg/kg (24 animals), 90 mg/kg (18 animals), or an equal volume of vehicle (23 animals), middle cerebral artery occlusion was produced in rats by means of an intraluminal suture technique. Reperfusion occurred after 1.5 (42 animals) or 2 hours (23 animals) of ischemia. Automated, volumetric measurements of 2',3',5'-triphenyl-2H-tetrazolium chloride-stained coronal brain sections demonstrated a statistically significant decrease in infarct size for MgSO4 treatment groups compared to controls. Cytoprotection was greater in animals subjected to 1.5 hours of ischemia (28.4% reduction in infarct volume, p < 0.001, Student's t-test), than in those having 2 hours of ischemia (19.3% reduction, p < 0.05). Animals given 90 mg/kg MgSO4 prior to 1.5 hours of ischemia (12 animals) showed a 59.8% reduction in infarct volume compared to controls (11 animals, p < 0.001) and a 43.1% reduction compared to the 30 mg/kg group (11 animals, p < 0.001). Analysis of variance demonstrated the statistically significant effects of MgSO4 doses on infarct volume across all groups (F = 22.95, p < 0.0001). The neuroprotective effect of intraarterial MgSO4 in this model is robust, dose dependent, and related to the duration of ischemia. The compound may be valuable for limiting infarction if given intraarterially before induction of reversible ischemia during cerebrovascular surgery.

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We evaluated the influence of a continuous intravenous infusion of 0.24 mg/kg PN 200-110 started 20 minutes before the induction of ischemia and continued for 2 hours on infarct size, histopathology, and neurological outcome in middle cerebral artery-occluded rats treated with PN 200-110 (n=8), placebo (n=7), or saline (n=8). Neurological examination was performed 24 hours after occlusion. We quantified infarct size by 2,3,5-triphenyl-tetrazolium chloride, hematoxylin and eosin, and Nissl staining and by computerized analysis of tracings of the infarcted areas and evaluated neuronal injury at the infarct periphery. The different types of ischemic cell damage were quantified by direct visual counting. We found no differences among saline-, placebo-, and PN 200-110-treated rats regarding infarct size, amount of neuronal alteration, and neurological outcome. Our results indicate the lack of a significant protective effect of this drug in experimental focal ischemia. (Stroke 1991^22:1064-1067) I n a search for effective cerebroprotective agents for use in neurosurgical practice, we became interested in dihydropyridine calcium antagonists. In another experimental study, 1 we demonstrated the therapeutic efficacy of nimodipine in lessening the extent of focal ischemia and the severity of peri-infarct neuronal injury. We explained these beneficial effects predominantly by the vasoactive properties of the drug, which increases cerebral blood flow (CBF) in the penumbra zone to above the ischemic threshold. Despite existing controversies regarding the mechanisms of the anti-ischemic action of calcium channel blockers, their most probable role is in restoration of tissue perfusion at the infarct periphery, rather than in protection of the neuronal cell by preventing Ca 2+ overload. 2 -6 On the other hand, some calcium antagonists are considered dangerous since they may worsen postischemic brain edema in experimental conditions by increasing the blood flow threshold for ion homeostasis (impaired membrane protection) and by increasing blood flow. Received December 5, 1990; accepted April 4, 1991. brain edema by using a new dihydropyridine calcium antagonist, PN 200-110. 1112 In this study we evaluated the cerebroprotective properties of this drug. Materials and MethodsWe permanently occluded the right middle cerebral artery (MCA) in 23 male Fischer-344 rats weighing 250-300 g by means of microsurgical transcTanial exploration and coagulation. 13 The MCA trunk was occluded by microbipolar coagulation from a point proximal to the origin of the lateral striate artery to 1 mm beyond where the vessel crosses the olfactory striae.14 The animals were anesthetized with 50 mg/kg i.m. ketamine HC1 and 2 mg/kg i.m. xylazine. The left femoral artery and vein were cannulated with polyethylene catheters to allow continuous blood pressure monitoring, arterial blood sampling, and drug administration. Animals were maintained at normothermia by external heating.Isradipine was donated by Sandoz AG, Nurenberg, FRG. Based on practical expe...