MECHANISMS OF PHARMACOLOGICAL CARDIOVERSION OF ATRIAL-FIBRILLATION BYCLASS-I DRUGS

Cardioversion of AF by Class I Drugs, Introduction: We recently develo ped a goat model of sustained atrial fibrillation (AF) in which repeti tive induction of AF by burst pacing shortened the atrial effective re fractory period (AERP) (electrophysiologic remodeling) and progressive ly prolonged the paroxysms of AF to become sustained (24 hours) within 1 to 3 weeks (atrial fibrillation begets atrial fibrillation), The ai m of the present study was to study the effect of Class I drugs in thi s animal model of chronic AF, Methods and Results: The effects of hydr oquinidine (HQ) on seven chronically fibrillating goats and of flecain ide (Fl) on nine goats were studied. Both drugs were infused intraveno usly until sustained AF was cardioverted or adverse drug effects occur red. HQ and Fl restored sinus rhythm in 86% and 67% of the cases. Adve rse drug effects occurred in 14% and 56%, respectively. The average at rial cycle length of AF (AFCL) was prolonged to a different degree, Ju st before restoration of sinus rhythm, the two drugs had increased AFC L by 72% and 50%, The duration of the QRS complex was prolonged 17% by HQ and 50% by Fl, The RR interval was not affected by HQ and was prol onged slightly by Fl, Directly after restoration of sinus rhythm, the AERP during pacing with an interval of 400 msec was 92 +/- 29 (HQ) and 66 +/- 10 msec (Fl) (control value: 149 +/- 10 msec), Intra-atrial co nduction velocity was 83 +/- 7 and 86 +/- 11 cm/sec (control value: 11 6 +/- 10 cm/sec), Although both drugs were effective in terminating AF , after cardioversion the atrial vulnerability was still very high and a single premature stimulus reinduced AF in 100% of the animals. As a result of the short AERP by the AF-induced remodeling and the depress ed intra-atrial conduction by the Class I drugs, directly after cardio version the atrial wavelength was abnormally short (between 5.7 and 7. 5 cm), This explains the still high atrial vulnerability to AF directl y after cardioversion by Class I drugs. Surprisingly, the prolongation of AFCL by either Class I drug was not due to lengthening of the func tional refractory period but rather to a widening of the excitable gap during AF, Conclusion: In a goat model of chronic AF, infusion of Cla ss IA and Class IC drugs restored sinus rhythm in 67% to 86% of the ca ses. However, due to the short AERP and the depressed intra-atrial con duction directly after cardioversion, the atrial vulnerability was sti ll very high and a premature beat easily reinduced AF.