Studies of antidote therapy for nisoldipine intoxication in experimental animals

In anesthetized rats under artificial respiration, intravenous infusion of nisoldipine (0.1 mg/kg x min) caused significant decreases in blood pressure, heart rate, cardiac output and peripheral resistance. The animals died 54.7 +/- 11.1 min after initiation of the infusion. The electrocardiogram showed sinus bradycardia, increasing AV blockade and displacement of the pacemaker into the AV node or the bundle of His. Survival time under nisoldipine infusion increased more than two-fold with simultaneous infusion of calcium gluconate, isoprenaline (isoproterenol) or dopamine. Norepinephrine (noradrenaline) had no significant effect on survival time; the latter decreased to 19.4 +/- 1.6 min by plasma volume expansion with polygeline. All antidotes prolonging survival time also normalized the cardiac output diminished after nisoldipine. Electrocardiographic changes were antagonized only by isoprenaline. Suitable antidotes for intoxication or over-dosage of nisoldipine are calcium salts as well as beta-sympathomimetic drugs; sheer volume substitution and peripheral vascular constriction should not be resorted to.