Nimodipine and chronic vasospasm in monkeys: Part 3. Cardiopulmonary effects.

ABSTRACT

A subarachnoid hemorrhage was induced in 30 cynomolgus monkeys by the placement of a 6- to 7-ml blood clot through a frontotemporal craniectomy (Day 0). The monkeys underwent a 1-week-long, randomized, blind trial comparing various doses of nimodipine to placebo, sham, and no treatment. The treatment groups were nimodipine, 3 mg/kg every 8 hours (n = 6), 6 mg/kg every 8 hours (n = 6), and 12 mg/kg every 8 hours (n = 6); placebo (polyethylene glycol 400), 0.33 ml/kg every 8 hours (n = 6); and no treatment (n = 6). An additional sham group underwent craniectomy without clot placement (n = 6) so that 36 animals in total were operated upon. Differences in cardiopulmonary indices between Day 0 and Day 7 were compared within and between groups. No significant differences were obtained in the sham and no treatment groups. The nimodipine 6- and 12-mg/kg groups showed significant decreases in blood pressure (P less than 0.04 and P less than 0.015). Systemic vascular resistance was increased in the placebo and 3-mg/kg groups (P less than 0.02) and decreased in the 12-mg/kg group (P less than 0.015). Stroke index was increased in the 12-mg/kg group (P less than 0.05). Cardiac index and stroke index correlated positively with nimodipine dosage (r = 0.99, P less than 0.05). There were no pronounced changes in pulmonary artery wedge pressure, central venous pressure, alveolar-arterial oxygen pressure difference, arteriovenous oxygen content difference, and percentage of shunting.