Comparative haemodynamic effects of lidocaine, mexiletine, and disopyramide
Beltrame, J.; Aylward, P.E.; McRitchie, R.J.; Chalmers, J.P.
Journal of Cardiovascular Pharmacology 6(3): 483-490
1984
ISSN/ISBN: 0160-2446 PMID: 6202976 Document Number: 240667
The effect of i.v. boluses of lidocaine (5 mg/kg), mexiletine (3.5 mg/kg) and disopyramide (5 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance, left ventricular end-diastolic pressure and peak rate of change of left ventricular pressure (peak LV dP/dt) were assessed in the conscious rabbit. Plasma levels for the 3 drugs corresponded to the human therapeutic range 3 min after administration. All 3 drugs had negative inotropic effects and reduced HR. Lidocaine reduced peak LV dP/dt by 26% mexiletine by 41% and disopyramide by 53%. The 3 drugs had quite different effects on CO as a result of differences in their actions on peripheral blood vessels: disopyramide caused a 21% fall in CO, associated with a significant vasconstriction; mexiletine did not lower CO, as it caused a substantial vasodilation; and lidocaine did not produce any substantial change in either CO or vascular resistance. Cardiac autonomic blockade did not alter these changes. Disopyramide evidently has a marked cardiodepressant effect, and although lidocaine depresses myocardial contractility in the conscious rabbit, it has little effect on other hemodynamic parameters. Mexiletine is evidently a more profound negative inotrope than lidocaine, but since it produces a significant fall in MAP and thus a reduction in afterload, the CO is maintained.