The cardiac effects of d- and l-disopyramide in normal subjects: a noninvasive study

Commercially available disopyramide is a racemic mixture of equal parts of dextrorotatory (d-) and levorotatory (l-) optical isomers. We studied the cardiac effects of i.v. administration of each isomer and the racemic mixture (dl-) in six normal males by digitized echocardiography, systolic time intervals and ECG. Both isomers and the racemic mixture produced equally marked dose-dependent negative inotropic effects (28.1 +/- 11.8% mean maximal reduction in fractional shortening of left ventricular dimension) and diastolic effects (28.6 +/- 24.1% mean maximal reduction in peak left ventricular filling rate). However, only the d-isomer prolonged QTc duration (by 13.6 +/- 5.2% at maximum, p less than 0.001 vs l-isomer). We conclude that disopyramide, in the doses used, produces marked adverse effects on left ventricle systolic and diastolic function in normal subjects independent of optical rotation. The production of these effects by the l-isomer without affecting QTc duration suggests different subcellular mechanisms for the myocardial depressant effects and some of the electrophysiologic effects of disopyramide.