The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent.
The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h)-reperfusion of the left anterior descending coronary artery. Compared to saline-treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Black
S C
SC
University of Michigan Medical School, Department of Pharmacology, Ann Arbor.
Chi
L G
LG
Mu
D X
DX
Lucchesi
B R
BR
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003645:Death, Sudden; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D015221:Potassium Channels; D013449:Sulfonamides; D000255:Adenosine Triphosphate; C063533:dofetilide