PROLONGATION OF INTRAVENTRICULAR-CONDUCTION TIME ASSOCIATED WITH FETAL IMPAIRMENT OF DEFIBRILLATION EFFICIENCY DURING TREATMENT WITH CLASS-I ANTIARRHYTHMIC AGENTS

To test whether fatal deterioration of defibrillation efficiency durin g antiarrhythmic therapy can be prevented by avoiding extreme decrease in ventricular conduction or toxic plasma drug levels, we determined the defibrillation threshold (DFT) before and during infusion of incre mental doses of disopyramide (n = 8), mexiletine (n = 9), or flecainid e (n = 9) in anesthetized dogs. Disopyramide did not alter DFT [from 4 .4 +/- 1.5 to 4.4 +/- 1.6 J (3.1 +/- 1.2 mu g/ml)]. Mexiletine tended to increase DFT from [4.6 +/- 1.2 to 6.1 +/- 2.0 J(1.8 +/- 0.6 mu g/ml ): p < 0.05], and defibrillation eventually was unsuccessful in 3 of t he 9 dogs. Although the plasma mexiletine level before refractory fibr illation was far beyond the human therapeutic range, prolongation of i ntraventricular conduction time (CT) was moderate (16 +/- 3%). Flecain ide increased DFT from 4.2 +/- 1.3 to 6.1 +/- 1.5 J at a plasma level of 1.04 +/- 0.37 mu g/ml (p < 0.0005). In 3 of 5 dogs that developed r efractory fibrillation, plasma flecainide level before terminal ventri cular fibrillation (VF) was not toxic, but prolongation of CT in the 5 dogs was remarkable (30 +/- 9%). Thus, VF resistant to defibrillation is not necessarily associated with both toxic plasma drug level and r emarkably decreased conduction. Reliability of these valuables as indi cators of fatally deteriorated defibrillation efficiency may vary amon g antiarrhythmic agents.