Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats

We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca²⁺, Na⁺, K⁺, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [¹⁴C]nicardipine into the brains of five rats; the highest concentrations of [¹⁴C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca²⁺ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-μg/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na⁺ and K⁺ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca²⁺ accumulation more than it reduces Na⁺ and water accumulation and K⁺ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca²⁺ entry into ischemic cells.