Improved myocardial function after cold storage with preservation solution supplemented with a carbon monoxide-releasing molecule (CORM-3)

Background: carbon monoxide-releasing molecules (CO-RMs) are pharmacologically active as they protect against cardiac graft rejection and cold ischemia-mediated renal dysfunction. We investigated the cardioprotective role of carbon monoxide (CO) released from CORM-3 against cold ischemia-mediated injury in the heart and evaluated its potential application in the clinical setting of cardiac transplantation. Methods: Isolated rat hearts underwent cold ischemic storage for 4 or 6 hours using St Thomas Hospital solution that was supplemented with either CORM-3 (50 mu mol/liter) or its inactive counterpart (iCORM-3), which does not release CO. Hearts were then reperfused. Both functional parameters and release of cardiac enzymes were assessed. Results: Addition of CORM-3 to the preservation solution resulted in a significant improvement in systolic and diastolic function as well as coronary flow when compared with hearts treated with iCORM-3. In addition, lower levels of the cardiac enzymes creatine kinase and lactate dehydrogenase were measured in the perfusate of hearts stored with CORM-3. Conclusions: The improved functional recovery and reduced enzyme release after cardiac cold storage with CORM-3, but not iCORM-3, indicate that CO is the main mediator of myocardial protection. Thus, CO-RMs can be used as adjuvants to improve the preservation of hearts for transplantation. J Heart Lung Transplant 2007;26:1192- 8. Copyright (c) 2007 by the International Society for Heart and Lung Transplantation.