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Impaired endothelium-derived hyperpolarizing factor-mediated relaxation in coronary arteries by cold storage with
Objectives:
University of Wisconsin solution is widely used to preserve organs for transplantation, but its effect on the individual endothelium-derived relaxing factors has not been studied. This study was designed to examine the effect of cold storage of the heart with University of Wisconsin solution on relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF).
Methods:
Porcine coronary artery rings were studied in organ chambers. Relaxation in response to the EDHFs stimuli bradykinin and A23187 in U46619 (30 nmol/L)-induced precontraction after incubation with University of Wisconsin solution (either at 37 degrees C in the oxygenated organ chamber or at 4 degrees C in a refrigerator for 4 hours) was compared with the control.
Results:
During the incubation, the coronary tone initially increased transiently (4.8 +/- 0.8 gm) and was subsequently reduced by 10.9 +/- 1.2 gm. Under both normothermia and hypothermia, after the incubation, the relaxation mediated by EDHF significantly decreased (under normothermia: from 68.7% +/- 10.2% to 32.1% +/- 8%, n = 7, p = 0.001, for bradykinin and from 79.9% +/- 8.4% to 56.9% +/- 8.5%, n = 7, p = 0.01, for A23187; under hypothermia and hypoxia: to 18.9% +/- 5.6%, n = 9, p = 0.0005, for bradykinin and 52.7% +/- 7.5%, n = 9, p = 0.03, for A23187). The incubation at normothermia also impaired the coronary smooth muscle contractility to U46619, but this contractility was preserved by cold storage.
Conclusions:
During cold storage, University of Wisconsin solution impairs the endothelium-dependent relaxation mediated by EDHF in the coronary circulation. This effect exists after the storage for at least 1 hour.