Effect of l-arginine on metabolic recovery of the ischemic myocardium

Background The release of nitric oxide is decreased after myocardial ischemia and reperfusion. Whereas the precursor l-arginine can stimulate the release of nitric oxide, its effect on metabolic recovery after myocardial ischemia is unknown. Methods To study the effect of l-arginine on metabolic recovery after myocardial ischemia, cardioplegia infusion, and reperfusion, 33 dogs were placed on cardiopulmonary bypass and subjected to a sequence of 30 minutes of normothermic global ischemia, 30 minutes of warm blood cardioplegic arrest, and 30 minutes of reperfusion. A pH probe was inserted in the anterior wall of the left ventricle, and tissue pH was measured throughout the experiment. Coronary blood flow in the left anterior descending coronary artery and the circumflex coronary artery was measured. Blood samples from the coronary sinus were taken to measure blood pH and levels of lactate, creatine kinase, and troponin T. Results In the control group of 9 dogs, tissue pH averaged 6.4 ± 0.1, 6.5 ± 0.1, and 6.8 ± 0.1 after the end of global ischemia, cardioplegia, and reperfusion, respectively. Tissue pH averaged 6.4 ± 0.1, 6.6 ± 0.1, and 6.9 ± 0.1, respectively, in the experimental group of 9 animals with 2 mmol/L of l-arginine added to the cardioplegic solution. Tissue pH averaged 6.2 ± 0.1, 6.7 ± 0.1, 7.1 ± 0.1, respectively, in the third group of 9 animals that received an additional infusion of l-arginine (10 mg · kg−1 · min−1) during reperfusion. Tissue pH recovered faster in groups with l-arginine (p = 0.00001). A hyperemic response of coronary blood flow was shown at reperfusion in animals in the control group only. In 6 dogs, l-NAME (n-nitroarginine methyl ester), an inhibitor of nitric oxide synthesis, was injected and resulted in a slower pH recovery on reperfusion compared with that of animals that received l-arginine. Conclusions The addition of l-arginine to the cardioplegic solution and the systemic circulation during reperfusion resulted in a significant increase in coronary blood flow during cardioplegia infusion and in a faster recovery of myocardial tissue pH, possibly by increasing coronary blood flow through the release of nitric oxide.