Nimodipine decreases resuscitability in a cardiopulmonary arrest model in the rat.
Although calcium has been implicated in ischemia-induced brain death or dysfunction, many animal studies do not show a beneficial effect of calcium-entry blockers given after resuscitation from a cardiopulmonary arrest (CPA). This may be due to the fact that treatment was started too late; we, therefore, evaluated the effect of the calcium-entry blocker nimodipine administered at the earliest feasible postischemic moment, i.e. at the start of the resuscitation attempts. In anesthetized Wistar rats, CPA was induced by an intra-cardiac injection of KCl, and maintained for 7 min by chest restriction. At the start of the resuscitation attempts, 50 rats were blindly and randomly assigned to intravenous treatment with either nimodipine (10 micrograms/kg over 2 min, followed by 1 micrograms/kg per min for 60 min; n = 25) or saline (n = 25). In the nimodipine group, significantly less rats could be resuscitated (11/25 versus 20/25) and the survival rate at the end of the 7 days evaluation period tended to be lower (5/25 versus 11/25). In the rats surviving after 7 days, there was no difference between both groups in incidence of seizures, neurological status and histological lesions in the hippocampus. It is concluded that nimodipine, in the dose tested and given during resuscitation in this rat model, has a detrimental effect on resuscitability and no beneficial effect on the neurological outcome in the surviving animals.
Calle
P A
PA
Department of Pharmacology, University of Gent Medical School, Belgium.
Bogaert
M G
MG
De Ridder
L
L
Buylaert
W A
WA
D000818:Animals; D002493:Central Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D006323:Heart Arrest / Q000150:complications / Q000628:therapy*; D009553:Nimodipine / Q000009:adverse effects* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012151:Resuscitation; D013997:Time Factors
D009553:Nimodipine