Musameh Muntaser D, Green Colin J, Mann Brian E, Fuller Barry J, Motterlini Roberto
Department of Surgery, Royal Free and University College London Medical School, Hampstead, London, UK.
J Heart Lung Transplant. 2007 Nov;26(11):1192-8. doi: 10.1016/j.healun.2007.08.005.
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.
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 mumol/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.
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.
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.
一氧化碳释放分子（CO-RMs）具有药理活性，因为它们可预防心脏移植排斥反应和冷缺血介导的肾功能障碍。我们研究了CORM-3释放的一氧化碳（CO）对心脏冷缺血介导损伤的心脏保护作用，并评估了其在心脏移植临床环境中的潜在应用。
使用补充了CORM-3（50微摩尔/升）或其无活性对应物（iCORM-3，不释放CO）的圣托马斯医院溶液，将离体大鼠心脏进行4或6小时的冷缺血保存。然后对心脏进行再灌注。评估功能参数和心脏酶的释放情况。
与用iCORM-3处理的心脏相比，在保存溶液中添加CORM-3可使收缩和舒张功能以及冠状动脉血流量显著改善。此外，在使用CORM-3保存的心脏灌注液中测得的心脏酶肌酸激酶和乳酸脱氢酶水平较低。
用CORM-3而非iCORM-3进行心脏冷保存后功能恢复改善且酶释放减少，表明CO是心肌保护的主要介质。因此，CO-RMs可作为佐剂用于改善心脏移植的保存。
