Effects of oral supplementation with L-citrulline on recovery from myocardial infarction in mice

In the heart, L-arginine can be metabolized to nitric oxide and citrulline or to urea and ornithine. During a heart attack, the heart undergoes enzymatic changes resulting in a down regulation of the nitric oxide pathway and an induction of the ornithine pathway. Nitric oxide is a vasodilator and improves cardiomyocyte contractility. Thus, an increase in nitric oxide should contribute to a shortened recovery time after a heart attack. We tested the hypothesis that increased blood levels of citrulline, a precursor of arginine, would increase cellular levels of arginine and the local concentration of nitric oxide during and after a heart attack. We gavaged mice daily with citrulline beginning a week prior to imposing a surgically-induced heart attack. The post-surgery recovery process was monitored by echocardiography. In addition, we bled these mice at intervals and measured amino acid concentrations in plasma. Each animal's echocardiogram data was analyzed against the blood arginine, citrulline, and ornithine levels.