Influence of acidosis on cardiotonic effects of colforsin and epinephrine: A dose-response study

Abstract

Objective: Acidosis produces a negative inotropic effect on cardiac muscle against which catecholamines and phosphodiesterase III inhibitors have limited therapeutic effects. This study evaluated the effects of colforsin, which directly activates adenylate cyclase without β-adrenergic receptor activation, in isolated Langendorff rat hearts in a pH- and concentration- dependent manner. Design: Experimental animal study. Setting: A university laboratory. Participants: Sprague-Dawley rats. Interventions: Hearts were isolated and perfused with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid/Tyrode solution (pH 7.4) in the Langendorff preparation. The hearts were assigned randomly to the control (pH 7.4), mild acidosis (pH 7.0), or severe acidosis (pH 6.6) group (n = 8 per group) and were perfused continuously with colforsin 10-7, 10-6, and 10-5 mol/L. Measurements and Main Results: Maximum dP/dt was determined, and the concentration-response relation was evaluated at each pH. Colforsin at 10 -6 mol/L increased the maximum dP/dt from 2,592 ± 557 to 5,189 ± 721 mmHg/s (p < 0.001) and from 1,942 ± 325 to 3,399 ± 608 mmHg/s (p < 0.001) in the control and mild acidosis groups, respectively; whereas colforsin, 10-5 mol/L, significantly increased the maximum dP/dt even in the severe acidosis group. No significant difference was seen in maximum dP/dt among the 3 groups after infusion with colforsin 10-5 mol/L. Conclusions: In contrast to catecholamines and other inodilators, colforsin at a high concentration restores decreased cardiac contractility against severe acidosis to an extent similar to physiologic pH. © 2013 Elsevier Inc. All rights reserved.