CRITICAL TIMING OF NITRIC-OXIDE SUPPLEMENTATION IN CARDIOPLEGIC ARREST AND REPERFUSION

Background It has been shown that increased nitric oxide (NO) generati on is associated with improved myocardial preservation during ischemia /reperfusion. This study sought to determine the optimal timing for NO supplementation in the setting of cardioplegic arrest, regional ische mia, and reperfusion. Methods and Results Isolated working rat hearts were arrested with normothermic oxygenated potassium cardioplegia for 5 minutes, followed by 60 minutes of normothermic continuous cardiople gic administration with left anterior descending coronary artery (LAD) occlusion. The hearts were divided into four groups. Hearts in group 1 were ischemic/reperfused controls without L-arginine treatment. Hear ts in group 2 were perfused with 3 mmol/L L-arginine for 5 minutes bef ore cardioplegic arrest. Hearts in group 3 were perfused with 3 mmol/L L-arginine in the cardioplegia solution. Hearts in group 4 were perfu sed with 3 mmol/L L-arginine for 5 minutes only during initial reperfu sion. Myocardial contractile function after 30 minutes of reperfusion was significantly better in group 2 compared with the other groups and was significantly lower in group 4 than group 1. Coronary flow, altho ugh decreased from base-line in all groups at 30 minutes of reperfusio n, was highest in group 2. The tissue accumulation of cGMP in groups 2 and 3 increased significantly after L-arginine infusion compared with the control group (group 1). In contrast, the LAD regional cGMP after reperfusion in group 4 was comparable to group 1 and significantly lo wer than groups 2 and 3, whereas the circumflex region cGMP in group 4 was significantly increased over group 1, comparable to groups 2 and 3. LDH release in groups 2 and 3 was significantly lower compared with groups 1 and 4. Conclusions As assessed by myocardial function and LD H release, L-arginine is most beneficial when given before cardioplegi c arrest, effective during cardioplegic arrest, and detrimental during reperfusion. This suggests that L-arginine given during reperfusion i s deleterious to optimal recovery of myocardial function in this ische mic model and that the effect of NO generation in the ischemic/reperfu sed myocardium may be dependent on the condition of the endothelium.