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 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.


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.
Musameh
Muntaser D
MD
Department of Surgery, Royal Free and University College London Medical School, Hampstead, London, UK.
Green
Colin J
CJ
Mann
Brian E
BE
Fuller
Barry J
BJ
Motterlini
Roberto
R
D000818:Animals; D002248:Carbon Monoxide; D050377:Cold Ischemia / Q000009:adverse effects / Q000379:methods; D003402:Creatine Kinase / Q000378:metabolism; D015925:Cryopreservation / Q000379:methods*; D006084:Graft Rejection / Q000517:prevention & control; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D016027:Heart Transplantation / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000201:enzymology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control
D019188:Organ Preservation Solutions; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002248:Carbon Monoxide; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase