PROLONGATION OF INTRAVENTRICULAR-CONDUCTION TIME ASSOCIATED WITH FETAL IMPAIRMENT OF DEFIBRILLATION EFFICIENCY DURING TREATMENT WITH CLASS-I ANTIARRHYTHMIC AGENTS
Y. Murakawa et al., PROLONGATION OF INTRAVENTRICULAR-CONDUCTION TIME ASSOCIATED WITH FETAL IMPAIRMENT OF DEFIBRILLATION EFFICIENCY DURING TREATMENT WITH CLASS-I ANTIARRHYTHMIC AGENTS, Journal of cardiovascular pharmacology, 25(2), 1995, pp. 194-199
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.