Antagonistic effects of epinephrine, glucagon and methylatropine but not calcium chloride against atrio-ventricular conduction disturbances produced by high doses of diltiazem, in conscious dogs.

Conscious dogs (n = 6) with chronically implanted electrocardiogram electrodes and arterial and venous catheters were infused with a large dose of diltiazem (1 mg/dog per min i.v. over 60 min) to evoke hypotension and atrioventricular disturbances (AVII and AVIII blocks) which lasted for several hours. These effects are also observed in humans after accidentally or intentionally taking overdoses of diltiazem and particularly verapamil. In the intoxicated dog, administration of methylatropine (50 micrograms/kg per min i.v. over 10 min), epinephrine (0.2 and 0.4 microgram/kg per min i.v. over 60 min) and glucagon (2 micrograms/kg/min i.v. over 15 min) but not CaCl2 (3 mg/kg/min i.v. over 15 min) abolished almost entirely the AVII and AVIII blocks produced by diltiazem and re-established a normal sinus rhythm. However, these treatments failed to normalize AV conduction, and did not modify the moderate hypotensive effects of diltiazem. These findings support available clinical observations that beta-adrenoceptors agonists, glucagon and atropine rather than calcium salts are beneficial for the successful treatment of cardiovascular toxicity associated with the intake of supratherapeutic doses of diltiazem or verapamil.