Reversal of cerebral arterial spasm by intrathecal administration of a calcium antagonist (nimodipine)

Abstract

Specific antagonists to the influx of calcium, necessary for the excitation-contraction coupling process in arterial smooth muscle, are potentially useful in the treatment of cerebral vasospasm but systemic hypotension might limit their clinical applicability. We studied the effect of the calcium antagonist nimodipine (BAY e 9736) on cerebral arterial spasm, intraventricular pressure and blood pressure (BP), when administered into the cerebral ventricles of the dog. Cerebral vasospasm was produced by the injection of autologous blood into the cisterna magna. In a group of 8 dogs, 100 micrograms of nimodipine was injected into the lateral ventricle. The effect of the drug on the basilar artery was monitored angiographically. Nimodipine always relieved spasm, and often the relaxation surpassed the resting vessel diameter. In a control group, the injection of placebo did not relax the spastic arteries. Determinations using gas chromatography of nimodipine in CSF and blood demonstrated that a concentration of 1 microgram/ml in cisternal CSF was sufficient to reduce spasm while concomitant plasma concentrations of 0.004 micrograms/ml did not result in significant BP reduction.

Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo

“…Nimo, Nimodipine nimodipine and therefore confirms previous promising results with intrathecal use of these two compounds [12-17, [24][25][26][27][28][29]32]. In the presented experimental setting they showed no significant difference in their efficacy.…”

“…Lack of prevention of CVS and systemic side effects with oral or intravenous administration led to experiments with topical application. Voldby et al [26] studied the effect of intrathecal bolus administration of calcium antagonist nimodipine after experimental SAH in dogs. Nimodipine always relieved spasm and often the relaxation surpassed the resting vessel diameter, whereas in a control group the injection of placebo did not relax the spastic arteries [26].…”

“…Voldby et al [26] studied the effect of intrathecal bolus administration of calcium antagonist nimodipine after experimental SAH in dogs. Nimodipine always relieved spasm and often the relaxation surpassed the resting vessel diameter, whereas in a control group the injection of placebo did not relax the spastic arteries [26]. Goia et al [27] and Zabramski et al [32] found beneficial effect on intrathecal nimodipine as opposed to systemic administration in reversing angiographic vasospasm in the two-hemorrhage and multihemorrhage canine models.…”

“…Whereas intravenous or oral administration of nimodipine does not appear to decrease the incidence of angiographic CVS [22,23], intraoperative bathing of vessels in nimodipine solution and intrathecal bolus administration has demonstrated reversal of spasm and dilatation of nonspastic vessels, without changes in mean arterial blood pressure [24][25][26][27][28][29]. The present study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing CVS in the rabbit SAH model in vivo.…”

“…1 Axial computer tomography demonstrates the successful dissemination of blood after cisterna magna injection. Arrow, Hyperdense prepontine blood collection canine models [26,27]. The rabbit's CSF volume was estimated to be 70-80 times less than that in humans and 5-10 times less than that in dogs [30,31].…”