Re-entrant ventricular arrhythmias in the late myocardial infarction period. 5. Mechanism of action of diphenylhydantoin.

Abstract

The mechanism of action of diphenylhydantoin (DPH) on re-entrant ventricular arrhythmias (RVA) was studied in dogs 3-7 days following ligation of the anterior descending coronary artery utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarction zone (IZ). DPH in a therapeutic dose consistently prolonged refractoriness of potentially RP in the IZ. This resulted in further impairment and/or block of conduction in the RP and was directly responsible for DPH ability to abolish RVA. On the other hand, DPH had no significant effect on conduction in the adjacent normal zone. Prior to abolition of RVA initiated by premature beats (PBs), DPH resulted in: 1) narrowing of the critical range of coupling intervals of PBs that resulted in re-entry (i.e., the re-entry zone), 2) shift of the narrowed re-entry zone to longer cardiac cycle lengths, and 3) lengthening of the coupling interval of the first re-entrant beat, as well as slowing the rate of re-entrant tachycardia. Thus DPH, similar to lidocaine, owes its antiarrhythmic action in RVS to its selective depressant effect on ischemic cells forming part of the RP.