Faculty Collaboration Database

One-day cold perfusion of bimakalim and butanedione monoxime restores ex situ cardiac function. Am J Physiol 1996 Nov;271(5 Pt 2):H1884-92

Date

11/01/1996

Pubmed ID

8945905

DOI

10.1152/ajpheart.1996.271.5.H1884

Scopus ID

2-s2.0-0029853987 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Bimakalim (Bim), an opener of ATP-sensitive K+ (KATP) channels, was given alone or with 2,3-butanedione monoxime (BDM), a reversible uncoupler of contractility, to protect myocardial function during 1 day of hypothermia. Left ventricular pressure (LVP), coronary flow (CF), percent O2 extraction (%O2E), and cardiac efficiency were measured in 96 isolated, perfused guinea pig hearts divided into seven groups: 1) cold control (no drugs); 2) BDM; 3) Bim; 4) BDM + Bim; 5) BDM + glibenclamide (Glib, a blocker of KATP channels); 6) BDM + Bim + Glib; and 7) time control (6 h warm perfusion only). Drugs were given before, during, and initially after 22 h of low CF at 3.8 degrees C. At 26 h (cold groups) or 4 h (warm group) LVP (mmHg; means +/- SE) was similar for time control (94 +/- 4) and BDM + Bim (92 +/- 4) groups, lower and equivalent in the BDM (65 +/- 7) and BDM + Bim + Glib (64 +/- 7) groups, but LVP was higher than in the Bim group (46 +/- 3), and lowest in the cold control (30 +/- 8) group. In addition, only in the BDM + Bim group were basal CF, %O2E, and cardiac efficiency returned to values obtained in the time control group. Epinephrine increased LVP to that of the time control (106 +/- 3) group only in the BDM + Bim group (106 +/- 3) after hypothermia, and CF increases with adenosine, 5-hydroxytryptamine, and nitroprusside were similar to that of the time control group only in the BDM + Bim group after hypothermia. All of the effects of Bim were reversed by Glib. These results indicate that Bim, given with BDM, effectively preserves myocardial function and metabolism as well as inotropic and vasodilatory reserve during long-term hypothermic preservation as if the 1-day hypothermic state had not been instituted. Because the beneficial effects of Bim are blocked by Glib, the protective effect of Bim likely results from maintained KATP channel opening. Treatment with exogenous KATP openers may prove useful in preserving cardiac function in the transplanted heart.

Author List

Stowe DF, Graf BM, Fujita S, Gross GJ

Author

David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Benzopyrans
Cold Temperature
Coronary Circulation
Diacetyl
Dihydropyridines
Drug Administration Schedule
Drug Combinations
Glyburide
Guinea Pigs
Heart
In Vitro Techniques
Myocardium
Oxygen Consumption
Perfusion
Pressure
Time Factors
Vasodilator Agents
Ventricular Function, Left