Myocardial and ventricular mechanics as influenced by disopyramide

The effects of disopyramide (D) on the mechanics of isolated myocardium as well as on the whole ventricle were examined in the rat model. Moreover bipolar leads of the apex and an area at the base of the left ventricle were set up to get indications for changes in the spread of excitation. D in concentrations of 10(-8) to 10(-4) mol/l did not affect the diastolic elastic properties of isolated myocardium. Isometric contraction amplitude was nearly unaltered, while rate of isometric contraction and relaxation were slightly increased. In the whole ventricle in situ D (2 to 10 mg/kg b.w. administered i.v.) induced a dose-dependent decrease in left ventricular isovolumetric peak pressure (16%), max.pos. dP/dt (40%) and max.neg. dP/dt (30%; for highest doses respectively), while time to peak pressure and relaxation time 90% were prolonged. Therapeutic dose of D (2 mg/kg b.w.i.v.) induced no decrease in essential systolic parameters of the whole ventricle under auxotonic conditions. Left ventricular pressure, dP/dt max.pos. and neg., left ventricular end-diastolic pressure and cardiac output were nearly unaltered. Heart rate showed a tendency to decrease, while total time of contraction and left ventricular ejection time increased. Higher doses of D led to marked cardiac depressant effects. The time interval between the excitation of the apex and an area at the base of the heart was increased. It was concluded that the negative dromotropic effect of D and thereby an altered pattern of left ventricular contraction are essential components in the elimination of the pressure gradient between left ventricle and aorta, observed in patients with muscular subaortic stenosis, and are presumably involved in the cardiac depressant effect of the drug in over-therapeutic doses.