BENEFICIAL EFFECT OF THE CALCIUM-SENSITIZING DRUG EMD-57033 IN A CANINE MODEL OF DILATED HEART-FAILURE

1. Pacing-induced heart failure was studied in eight dogs, Heart failu re was induced by right ventricular pacing at 250-260 beats/min for 6 weeks. Evidence of heart failure was determined clinically and by meas urement of left ventricular (LV) dimensions by transoesophageal echoca rdiography. 2. Haemodynamic measurements of LV pressure, maximum rate of rise of LV pressure (LVdP/dt(max)), cardiac output, mean arterial p ressure, heart rate, pulmonary artery and pulmonary wedge pressures we re made during infusion of solvent (control) and the calcium sensitize r EMD 57033 (0.6 mg min(-1) kg(-1)). 3. The degree of heart failure va ried from mild to severe in different individuals, but in each case EM D 57033 exerted a positive inotropic effect on LV haemodynamics and di mension. 4. The positive inotropic effect of the calcium sensitizer wa s manifest by increased peak LVdP/dt with a subsequent increase in car diac output at the same mean arterial pressure. 5. This study clearly demonstrates that there is the potential for improvement of contractil ity of the failing myocardium of the intact mammal by an agent with a mechanism of action which does not involve an increase in intracellula r calcium.