Cardioprotection by Activation of NO/cGMP Pathway After Cardioplegic Arrest and 8-Hour Storage

Background. We determined whether activation of the nitric oxide/cyclic guanosine monophosphate pathway by sodium nitroprusside (SNP) protects hearts subjected to cardioplegic arrest and prolonged hypothermic storage. Methods. Isolated rat hearts arrested with St. Thomas’ II cardioplegia and stored at 3° ± 1°C for 8 hours were reperfused at 37°C in Langendorff (10 minutes) and working (60 minutes) modes. Results. During reperfusion, left ventricular work was depressed in stored hearts relative to fresh hearts. When present during arrest, storage, and both reperfusion phases, SNP (200 μmol/L) improved work to values close to those in fresh hearts. When added only during the 10-minute period of Langendorff reperfusion, SNP also improved the subsequent recovery of work. This effect was antagonized by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Poststorage coronary perfusion was not increased by SNP. 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 nitric oxide/cyclic guanisine monophosphate pathway. These results suggest that supplementing cardioplegic solutions with SNP, administering SNP during early reperfusion, or both may offer additional means to improve donor heart preservation.