Glucagon Antagonism of Calcium Channel Blocker-Induced Myocardial Dysfunction

摘要

This study evaluated the interaction between glucagon and three different calcium channel blockers (CCBs). Using an isolated rat heart preparation, glucagon antagonized myocardial depression produced by verapamil, diltiazem, and nifedipine, which represent three classes of CCBs. Complete antagonism of diltiazem-induced myocardial depression was achieved with 5 x 10 to the minus 7th power M glucagon. Assuming glucagon (MW = 3485 daltons) is initially distributed within the plasma volume (volume of distribution = 40 ml/kg), a plasma concentration of 5 x 10 to the minus 7th power M can be easily obtained in vivo as it would require only 5 mg in a 70-kg man. Based on these results, glucagon may be an effective agent to rapidly reverse myocardial toxicity resulting from CCB administration. Glucagon has been used to antagonize myocardial depression resulting from beta-blocker overdose or toxicity. In dogs, glucagon antagonizes the myocardial depressant effects of quinidine and procainamide. Glucagon also reverses the hypotension of verapamil overdose in rats, but its ability to antagonize other CCBs has not been previously examined. Reprints. (AW)