Electrophysiologic effects of civamide (Zucapsaicin) on canine cardiac tissue in vivo and in vitro

The cardiac electrophysiologic effects of civamide (zucapsaicin), the cis-i somer of the alkyl vanillylamide, capsaicin, were evaluated in intact dogs and isolated Purkinje fibers. In anesthetized dogs, the mechanism of ventri cular tachycardia inducible from 1 to 3 h after coronary artery occlusion w as determined by activation mapping. Of 16 dogs studied, nine had ventricul ar tachycardia of focal endocardial origin; four, a reentrant mechanism; an d three had no inducible arrhythmia. Civamide (50 mu g/kg) was administered to 10 of 13 dogs that were inducible, but three dogs were used as time con trols. Transmural activation times were unaltered by civamide, but mean art erial pressure decreased from 76 +/- 10 to 66 +/- 10 mm Hg (p < 0.05), and muscle refractory periods shortened from 138 +/- 3 to 132 +/- 4 ms (p < 0.0 5). Civamide altered inducibility in five of six dogs with ventricular tach ycardia of focal endocardial origin, but those with epicardial reentrant me chanisms were not affected in three of four dogs. With microelectrode techn iques in vitro, civamide (10(-5) M) shortened the action-potential duration at 50% repolarization (APD(50)) from 193 +/- 13 to 177 +/- 12 ms (p < 0.01 ) and APD(90) from 260 +/- 15 to 248 +/- 13 ms (p < 0.01) in isolated Purki nje fibers (n = 10). Nifedipine prevented the effects of civamide in vitro. These results show that civamide may alter inducibility of ventricular tac hycardia with focal endocardial origin and shorten APD of Purkinje fibers i n vitro. The effects of civamide in vitro are prevented by preexposure of t he Purkinje fibers to nifedipine, suggesting that the electrophysiologic ef fects of civamide may be mediated through blockade of calcium channels.