QUINIDINE PHARMACODYNAMICS IN NORMAL AND ISOPROTERENOL-INDUCED HYPERTROPHIED BLOOD-PERFUSED WORKING RABBIT HEARTS

Ventricular hypertrophy is associated with several electrophysiologic abnormalities. However, little is known about the pharmacodynamics of antiarrhythmic drugs in the setting of ventricular hypertrophy. We stu died the myocardial accumulation and pharmacodynamics of quinidine in 10 control rabbit hearts and 10 with isoproterenol-induced hypertrophy . Hearts were perfused in the working heart configuration. Electrophys iologic measurements were made at low afterload (30 cm H2O) and high a fterload (60 cm H2O) at baseline and during quinidine perfusion (972 n g/ml). The myocardial quinidine concentration measured at the end of e ach experiment was significantly lower in the hypertrophied hearts (25 .0 +/- 11.7 mu g/g) as compared with the control hearts (51.2 +/- 12.7 mu g/g, p < 0.001). The left ventricular (LV) monophasic action poten tial (MAP) duration was significantly shorter in the hypertrophied hea rts as compared with control hearts at low afterload (166 +/- 27vs. 19 2 +/- 24ms, p < 0.01) and at high afterload (141 +/- 7vs. 171 +/- 24 m s, 24 ins, p < 0.01). Quinidine prolonged MAP duration to a similar ex tent in both hypertrophied and control hearts; the MAP prolongation oc curred at both low (192 +/- 21 vs, 223 +/- 25 ms, p < 0.02) and high a fterloads (179 +/- 15 vs, 216 +/- 20 ms, p < 0.01) in the hypertrophie d and control hearts, respectively. However, the ratios of the changes in electrophysiologic parameters to quinidine myocardial concentratio ns were greater In the hypertrophied hearts than in control hearts (p < 0.05). Therefore, AP duration (APD) is significantly shortened in is oproterenol-induced hypertrophy. The magnitude of quinidine effects on MAP duration and ventricular effective refractory period (VERP) are s imilar in hypertrophied hearts and control hearts, but the myocardial concentration-effect relations are increased significantly in hypertro phy hearts.