@article{oai:tsukuba.repo.nii.ac.jp:00029427,
 author = {高橋, 宏 and 猪股, 伸一 and 田中, 誠 and Hagiya, Keiichi and Takahashi, Hiroshi and Isaka, Yumi and Inomata, Shinichi and Tanaka, Makoto},
 issue = {5},
 journal = {Journal of cardiothoracic and vascular anesthesia},
 month = {Oct},
 note = {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.},
 pages = {925--932},
 title = {Influence of Acidosis on Cardiotonic Effects of Colforsin and Epinephrine: A Dose-Response Study},
 volume = {27},
 year = {2013}
}