title: 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.
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  A university laboratory.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department of Anesthesiology, University of Tsukuba, Tsukuba City, Japan. Electronic address: hagiya916@yahoo.co.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hagiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Isaka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Inomata
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000138:Acidosis / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D005576:Colforsin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D005576:Colforsin; D004837:Epinephrine