title: Electrophysiologic effects of civamide (zucapsaicin) on canine cardiac tissue in vivo and in vitro.
abstract: The cardiac electrophysiologic effects of civamide (zucapsaicin), the cis-isomer of the alkyl vanillylamide, capsaicin, were evaluated in intact dogs and isolated Purkinje fibers. In anesthetized dogs, the mechanism of ventricular tachycardia inducible from 1 to 3 h after coronary artery occlusion was determined by activation mapping. Of 16 dogs studied, nine had ventricular tachycardia of focal endocardial origin; four, a reentrant mechanism; and three had no inducible arrhythmia. Civamide (50 microg/kg) was administered to 10 of 13 dogs that were inducible, but three dogs were used as time controls. Transmural activation times were unaltered by civamide, but mean arterial 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 < 0.05). Civamide altered inducibility in five of six dogs with ventricular tachycardia of focal endocardial origin, but those with epicardial reentrant mechanisms were not affected in three of four dogs. With microelectrode techniques in vitro, civamide (10(-5) M) shortened the action-potential duration at 50% repolarization (APD50) from 193 +/- 13 to 177 +/- 12 ms (p < 0.01) and APD90 from 260 +/- 15 to 248 +/- 13 ms (p < 0.01) in isolated Purkinje fibers (n = 10). Nifedipine prevented the effects of civamide in vitro. These results show that civamide may alter inducibility of ventricular tachycardia with focal endocardial origin and shorten APD of Purkinje fibers in vitro. The effects of civamide in vitro are prevented by preexposure of the Purkinje fibers to nifedipine, suggesting that the electrophysiologic effects of civamide may be mediated through blockade of calcium channels.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
authors.forename: D O
authors.initials: DO
authors.lastname: Arnar
authors.forename: J J
authors.initials: JJ
authors.lastname: Cai
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: J B
authors.initials: JB
authors.lastname: Martins
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; C117479:zucapsaicin; D009543:Nifedipine; D002211:Capsaicin