'Early' ischemia and reperfusion-induced arrhythmias: antiarrhythmic effects of diltiazem in the conscious rat.
The ability of diltiazem to prevent early ischemia and reperfusion-induced arrhythmias was investigated in conscious rats with coronary artery occlusion. During a 30-min period of occlusion of the left coronary artery, 100% of placebo-treated animals exhibited ventricular tachycardia, 65% exhibited ventricular fibrillation and the mean total number of premature ventricular complexes was 1076 +/- 254. Diltiazem (0.5 or 2.0 mg/kg body weight, given intravenously 10 mins prior to coronary occlusion), reduced the incidence of ventricular tachycardia to 62% (P less than 0.01) and 54% (P less than 0.001), respectively and the incidence of ventricular fibrillation to 31% (P = NS) and 15% (P less than 0.01), respectively. The total number of premature ventricular complexes was also reduced to 248 +/- 78 (P = NS) and 156 +/- 55 (P less than 0.02). The development of ST segment elevation, induced by coronary artery occlusion, was delayed in both drug-treated groups. Similarly, diltiazem, at the same doses, reduced the incidence of ventricular fibrillation induced by reperfusion after 5 mins of coronary artery occlusion from 100% to 50% (P less than 0.01) and 25% (P less than 0.001) and mortality from 87% to 42% (P less than 0.02) and 25% (P less than 0.01), respectively. The anti-arrhythmic effects of diltiazem were not related to changes in heart rate and all groups showed similar occluded zone sizes, as measured by a fluorescent microsphere technique. Thus, diltiazem affords substantial protection against both early ischemia-induced ventricular arrhythmias and reperfusion-induced arrhythmias and this action may be associated with the beneficial effects on ischemia-induced ST segment elevation.
Kinoshita
K
K
Rayne Institute, St Thomas' Hospital, London, United Kingdom.
Hearse
D J
DJ
Braimbridge
M V
MV
Manning
A S
AS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014693:Ventricular Fibrillation / Q000503:physiopathology
D004110:Diltiazem