[Comparative studies on the cardiodepressant effect of disopyramide, mexiletine and propafenon]

The effect of clinical antiarrhythmic doses of disopyramide (Di), mexiletine (Me), and propafenon (Pr) on cardiac function was studied in 7 normal volunteers by M-mode echocardiography and the extent of functional changes caused by the three drugs was compared. For each of the substances echocardiographic parameters of left ventricular function were determined before injection, 5-25 min. after an intravenous administration (Di 2.0 mg/kg, Me 3.0 mg/kg, Pr 1.5 mg/kg) at intervals of 5 min., and after 3 days of oral therapy (Di 4 X 200 mg/day, Me 4 X 200 mg/day, Pr 3 X 300 mg/day). Di, Me, and Pr each showed significant negative inotropic activity, though of varying degree. For each drug the effect was more pronounced after intravenous administration than under oral therapy. Maximum decreases in myocardial contraction occurred 5-15 min. after termination of injection, with an increase in endsystolic diameter (Di 30.3%, Me 13.6%, Pr 9.7%), no change in preejection diameter, and a reduction in the percentage and velocity of mean circumferential fiber shortening and systolic ventricular wall thickness (Di 18.1%-45.1%, Me 9.6%-23.7%, Pr 11.8%-16.7%). While the cardiodepressant activity of orally administered Di, Me and Pr did not statistically differ, for the first 20 min. after intravenous administration Di exhibited a marked negative inotropic effect that was significantly greater than those of Me and Pr. In view of the considerable hemodynamic side effects of Di, Me, and Pr observed in this study, the benefit to risk ratio must be evaluated carefully and individually before commencement of antiarrhythmic therapy. Because of its acute and pronounced cardiodepressant activity, intravenous Di should be used with particular caution; a dose reduction and slow injection are recommended in patients with left ventricular dysfunction.