Comparative study of the effect of slow channel inhibiting agents on ischemia-induced conduction delay as relevant to the genesis of ventricular fibrillation.
Conduction delay has been shown to be an important factor in the genesis of ventricular fibrillation (VF). We evaluated the relationship between conduction delay and (1) initiation of VF and (2) the effects of Ca++ blockers on conduction delay in 41 dogs: eight control (nontreated, non-VF); nine ischemic VF; eight verapamil-treated (0.15 mg/kg bolus followed by 7.5 micrograms/kg/min); eight diltiazem-treated (20 micrograms/kg/min); and eight nifedipine-treated (0.1 mg/kg bolus). Propagation of electrically-induced premature impulses from the midmyocardial bipole of one transmural electrode was recorded at epicardial and endocardial bipoles of other electrodes before and 5, 15, and 30 minutes after coronary ligation. Conduction delay (i.e., conduction times compared to preligation levels) of VF, verapamil, diltiazem, and nifedipine groups were compared to control group in normal and in the center and border of ischemic zones in both base to apex (anterograde) and apex to base (retrograde) directions. Results showed that there was no change in conduction delay in the normal zone between control and VF groups or the treated groups, but both in the center and border of ischemic zone VF was quantitatively related to conduction delay and Ca++ blockers, except that nifedipine significantly reduced conduction delay. We conclude that our model provides a new approach to the assessment of anti-VF intervention. Further, verapamil and diltiazem appear to be useful agents in reducing the risk of ischemia-induced reentrant ventricular tachyarrhythmias.
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy; D004110:Diltiazem / Q000008:administration & dosage; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology*; D014700:Verapamil / Q000008:administration & dosage
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine