Effects of nimodipine on acute focal cerebral ischemia.

Abstract

SUMMARY Nimodipine is a calcium slow channel blocker with several pharmacologlc properties suggesting the potential to favorably modify outcome in focal cerebral ischemia. Thirty adult cats underwent unilateral middle cerebral artery (MCA) occlusion for 4 hours. Seventeen cats were treated with an ipsilateral intracarotid infusion of nimodipine (1 /xg kg" 1 min ~') beginning 15 minutes before MCA ocdusion and continuing throughout the occlusion period. Eight nimodipine treated cats maintaining MAP > 90 mmHg were assigned to a Higher Pressure Nimodipine (HPN) group. The remaining nine treated cats with MAP < 90 mmHg were assigned to the Lower Pressure Nimodipine (LPN) group. Thirteen cats were untreated, receiving an isovolumetric amount of vehicle through the ipsilateral carotid artery. Local cerebral blood flow (1CBF) was continuously monitored using thermal diffusion probes. The brains, assessed for colloidal carbon perfusion, fluorescein and Evans blue staining, electroencephalographic activity (EEG), and histological changes, revealed no significant differences by any of these methods between the HPN and control animals with the exceptions of: 1) HPN treated cats exhibited a preservation of EEG activity at 15 minutes post-occlusion compared to the untreated cats, and 2) Post-iscbemic surface colloidal carbon perfusion was better preserved in the treated cats than hi the untreated cats. Mild hypotension, as demonstrated by the LPN group, negated these two positive effects. Prior to MCA occlusion, 1CBF was bilaterally significantly increased after nimodipine infusion in the HPN group as compared to vehicle infusion. Intra-arterially infused nimodipine did not reduce infarct size.

Nimodipine has no effect on the cerebral circulation in conscious pigs, despite an increase in cardiac output

“…Indeed, in experiments involving ligation of a cerebral artery (Steen et al, 1983;Smith et al, 1983;Mohamed et al, 1985;Newberg Milde et al, 1986) or experimental subarachnoid haemorrhage (McCalden et al, 1986) impairment of cerebral blood flow, due to an increase in vasomotor tone in the post-ischaemic or post-haemorrhagic phase, can be alleviated by nimodipine. However, negative reports have also been published (Barnett et al, 1986;Schuier & Ulrich, 1987;Sahlin et al, 1987;Berger & Hakim, 1988). From the present and other studies the question arises whether the differences in results can be explained by differences in preparations only (conscious versus anaesthetized, open versus closed skull) or that differences in species may be the dominant factor.…”

Nimodipine does not improve neurologic outcome after 14 minutes of cardiac arrest in cats.

“…It has been reported that mild hypotension induced by phlebotomy (MAP < 90 mm Hg) negates the beneficial effects of nimodipine on EEG recovery and reperfusion (colloidal carbon filling) following regional cerebral ischemia in cats. 4 Thus, we cannot exclude the possibility that differences in MAP between groups may have affected neurologic outcome. The effects of NE and TMP on postischemic brain are not known with certainty.…”

Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia.

“…- 22 In our study we limited the recirculation period after ischemia to 3 hours. Within that period an evident improvement with nimodipine treatment was found in the morphologic appearance of CA, neurons in the hippocampus; EEG activity after ischemia returned significantly sooner and the appearance of final recordings after 2 hours of recirculation was much better than in control rabbits.…”