Share this article on:

OPENING OF MITOCHONDRIAL POTASSIUM CHANNELS: A New Target for Graft Preservation Strategies?

Kevelaitis, Egidijus1; Oubenaissa, Abdéslam2; Mouas, Christian2; Peynet, Jacqueline3; Menasché, Philippe4 5

Experimental Transplantation

Background. This study was designed to assess the protective effects of the mitochondrial adenosine triphosphate-sensitive potassium channel (K ATP) opener diazoxide as an additive to heart preservation solution.

Methods. Forty isolated isovolumic buffer-perfused rat hearts were divided into four groups. Groups I and III hearts were arrested with and cold-stored in Celsior solution for 4 hr and 10 hr, respectively. In Groups II and IV, hearts underwent a protocol similar to that used in Group I and III, respectively, except that Celsior was supplemented with 100 μmol/L of diazoxide.

Results. The protective effects of diazoxide were primarily manifest as a better preservation of diastolic function and a reduction of myocardial edema. The improvement of postischemic systolic function was observed only after prolonged exposure to diazoxide in Group IV, compared with Group III. The endothelium-dependent and endothelium-independent coronary flow postischemic responses were not affected by the supplementation of Celsior with diazoxide.

Conclusions. Pharmacologic activation of mitochondrial K ATP channels seems to be an effective means of improving preservation of cold-stored hearts, which is consistent with the presumed role of these channels as end effectors of the cardioprotective preconditioning pathway.

Departments of Cardiovascular Surgery and Biochemistry, and INSERM U-127, Hôpital Lariboisière, 75475 Paris Cedex 10, France; and Department of Physiology, Kaunas Medical University, 3000 Kaunas, Lithuania

1 Department of Physiology.

2 INSERM U-127.

3 Department of Biochemistry.

4 Department of Cardiovascular Surgery.

Received 23 September 1999.

Accepted 8 March 2000.

5 Address correspondence to: Philippe Menasché, M.D., Ph.D., Department of Cardiovascular Surgery, Hôpital Bichat, 46, rue Henri Huchard, 75018 Paris, France.

© 2000 Lippincott Williams & Wilkins, Inc.