BACKGROUND: Hearts treated with l-arginine polymers have demonstrated upregulated production of nitric oxide. The current study examined whether these polymers improved coronary flow and reduced myocardial oxidative stress after rat heart transplantation. METHODS: PVG donor hearts were incubated ex vivo with either 100 mumol/L l-arginine polymers 9 amino acids in length (R9) (n = 7) or phosphate-buffered saline (n = 7) for 30 minutes after arrest and then transplanted heterotopically into the abdomen of ACI recipient rats. Coronary flows were assessed using fluorescent microspheres both at baseline (30 minutes after reperfusion) and at 6 hours and compared using the paired Student t test. Evidence of oxidative stress was assessed in a separate cohort of similarly treated animals by enzyme-linked imunosorbent assay for rat tumor necrosis factor-alpha at 6 hours. RESULTS: Histochemistry with biotinylated l-arginine polymers demonstrated uptake of R9 into the vascular walls of treated allografts. Although all hearts experienced deterioration in coronary flow between baseline and 6 hours, the R9-treated group had a smaller reduction (29.9%, P =.10) than the phosphate-buffered saline control group (58.0%, P =.003). Tumor necrosis factor-alpha levels were also significantly reduced in the R9 treatment group compared with the phosphate-buffered saline category (160 +/- 30 versus 205 +/- 38, P =.007). CONCLUSION: Rat cardiac allografts treated with R9 at the time of procurement exhibited less deterioration in coronary flow and a reduction in myocardial oxidative stress than the phosphate-buffered saline control group in the perioperative period. The use of arginine polymers may thus provide important myocardial protection against ischemia-reperfusion injury in both transplant and routine cardiac surgery cases.