The effect of nimodipine on post-ischemic cerebral glucose utilization and blood flow in the rat

Abstract

The authors hypothesized that pretreatment with the calcium entry blocker nimodipine would preserve cerebral glucose utilization and maintain favorable brain flow after cerebral ischemia. Three groups of pentobarbital anesthetized rats were studied: control (group 1), ischemia (group 2), and ischemia plus nimodipine pretreatment, 1 mg · kg-1 ip, 1 h prior to ischemia (group 3). Forebrain ischemia was induced with bilateral carotid clamping, administration of trimetaphan, and blood withdrawal to obtain a mean arterial pressure of 50 mmHg. The carotid clamps were released and blood re-infusion was begun 9 min after the onset of an isoelectric EEG signal. Ten minutes later, determination of regional cerebral glucose utilization (rCGU) was begun by injecting 3H-2-deoxyglucose in saline. After 60 min of reperfusion, regional cerebral blood flow (rCBF) was determined by the indicator fractionation method, using 14C-iodoantipyrine. The brain was divided into hemisphere, diencephalon, cerebellum, and brainstem. Tissue radioactivities were determined by standard techniques. Compared to group 1, hemispheric rCGU (mean ± SEM, μmoles · 100 g-1) was significantly (P < 0.05) reduced groups 2 and 3 (40 ± 3 vs 27 ± 2 and 22 ± 2). Hemispheric rCGU was not significantly different in groups 2 and 3. Group 2 exhibited significantly (P < 0.05) reduced rCBF (mean ± SEM, ml · 100 g-1 · min-1) in the hemispheres compared to control (85 ± 6 vs 135 ± 17). However, nimodipine pretreatment prevented this post-ischemic hypoperfusion in group 3 (133 ± 18). Regional CBF to non-ischemic regions, i.e., diencephalon and cerebellum, was not significantly reduced in group 2, but it was increased in group 3 compared to control. Nimodipine favorably influences reperfusion at 1 h after forebrain ischemia, but it does not affect post-ischemic regional hypometabolism in the early period of reperfusion and increases flow to non-ischemic brain.