Reduced positive inotropic effects in diseased human ventricular myocardium

Abstract

In isolated contracting human ventricular myocardium taken from patients undergoing mitral valve replacement the positive inotropic effects of calcium, isoprenaline, dobutamine, dopamine, histamine, milrinone, isobutylmethylxanthine, and theophylline were determined. Calcium (15 mmol·litre⁻¹) produced an increase in force of contraction similar to that of a maximal effective concentration of ouabain (1 × 10⁻⁷ mol·litre⁻¹); significantly lower maximal effects were measured with all the other positive inotropic compounds tested. The addition of these positive inotropic substances after a stable maximum effect with ouabain (1 × 10⁻⁷ mol·litre⁻¹) had been reached increased the incidence of toxicity without producing any further inotropic effects. These results suggest that inotropic substances acting through cyclic adenosine monophosphate give less than the maximum inotropic response in isolated muscle from diseased human hearts, which is not additive to the maximal ouabain induced inotropy.