Attenuation of reperfusion-induced ventricular fibrillation in the rat isolated hypertrophied heart by preischemic diltiazem treatment.
The ability of the calcium antagonist diltiazem to protect against reperfusion-induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4 +/- 32.3) compared with 27 seconds (mean 110.6 +/- 36.6; p < 0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 micrograms reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 micrograms diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p < 0.01), and sustained VF from 82% to 8% (p < 0.01). Median VF duration in this group was reduced to 0 seconds (p < 0.05; mean 24.7 +/- 22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Baxter
G F
GF
Department of Pharmacology, De Montfort University, Leicester, UK.
Yellon
D M
DM
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control*
D004110:Diltiazem