CARDIOPROTECTION BY ACTIVATION OF NO CGMP PATHWAY AFTER CARDIOPLEGIC ARREST AND 8-HOUR STORAGE/

Background. We determined whether activation of the nitric oxide/cycli c guanosine monophosphate pathway by sodium nitroprusside (SNP) protec ts hearts subjected to cardioplegic arrest and prolonged hypothermic s torage. Methods. Isolated rat hearts arrested with St. Thomas' II card ioplegia and stored at 3 degrees +/- 1 degrees C for 8 hours were repe rfused at 37 degrees C in Langendorff (10 minutes) and working (60 min utes) modes. Results. During reperfusion, left ventricular work was de pressed in stored hearts relative to fresh hearts. When present during arrest, storage, and both reperfusion phases, SNP (200 mu mol/L) impr oved work to values close to those in fresh hearts. When added only du ring the 10-minute period of Langendorff reperfusion, SNP also improve d the subsequent recovery of work. This effect was antagonized by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxal in-1-one (ODQ). Poststorage coronary perfusion was not increased by SN P. Conclusions. The ability of SNP to enhance recovery independent of changes in coronary perfusion and in an ODQ-sensitive manner suggests that SNP-induced protection is due to activation of the myocardial nit ric oxide/cyclic guanisine monophosphate pathway. These results sugges t that supplementing cardioplegic solutions with SNP, administering SN P during early reperfusion, or both may offer additional means to impr ove donor heart preservation. (C) 1998 by The Society of Thoracic Surg eons.