Influence of Acidosis on Cardiotonic Effects of Colforsin and Epinephrine: A Dose-Response Study

• Published in: Journal of cardiothoracic and vascular anesthesia Vol. 27; no. 5; pp. 925 - 932
• Main Authors: Hagiya, Keiichi, MD, Takahashi, Hiroshi, MD, Isaka, Yumi, Inomata, Shinichi, MD, Tanaka, Makoto, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2013
• Subjects: acidosis; Acidosis - drug therapy; Acidosis - physiopathology; adenylate cyclase; Anesthesia & Perioperative Care; Animals; Cardiotonic Agents - administration & dosage; colforsin; Colforsin - administration & dosage; Critical Care; cyclic adenosine monophosphate; Dose-Response Relationship, Drug; Epinephrine - administration & dosage; Male; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; cyclic adenosine monophosphate; adenylate cyclase; colforsin; acidosis
• ISSN: 1053-0770; 1532-8422
• DOI: 10.1053/j.jvca.2012.09.019

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.