Effect of l-arginine cardioplegia on recovery of neonatal lamb hearts after 2 hours of cold ischemia

Background.: Despite hypothermia and cardioplegia, myocardial ischemia followed by reperfusion results in both ventricular and endothelial dysfunction. The endothelial dysfunction is characterized by a reduced response to acetylcholine, which implies a reduced ability of the endothelium to release nitric oxide after hypothermic ischemia and reperfusion. We have previously demonstrated that infusion of the nitric oxide precursor l-arginine only during reperfusion after hypothermic ischemia significantly improves the recovery of ventricular function and results in an increased vasodilator response to the infusion of acetylcholine. In contrast, other investigators have found that nitric oxide has deleterious effects during postischemic reperfusion. Methods.: In the current experiments we have further examined the role of endothelial production of nitric oxide by adding 10 mmol/L l-arginine to cardioplegia in isolated, blood-perfused neonatal lamb hearts having 2 hours of cold cardioplegic ischemia. In another group 10 mmol/L d-arginine, an inactive enantiomer of l-arginine, was added to the cardioplegia. Controls received only cardioplegia (dextrose-potassium). Results.: At 30 minutes of reperfusion, the l-arginine group showed a significantly improved recovery in left ventricular systolic function (maximum developed pressure, developed pressure at a constant balloon volume [V10] resulting in an end-diastolic pressure of 10 mm Hg before ischemia, positive maximum dP/dt, and dP/dt at V10), diastolic function (negative maximum dP/dt and end-diastolic pressure at V10), coronary blood flow, endothelial function (assessed by the coronary vascular resistance response to acetylcholine), and myocardial oxygen consumption compared with the control group (p < 0.05). There were no significant differences in the recovery of any variables between the d-arginine and control groups. Conclusions.: These results suggest that provision of more substrate for the endothelial production of nitric oxide during ischemia has an important salutary effect on the recovery of postischemic myocardial and endothelial function and provide further evidence for an important role for the endothelial production of nitric oxide in the response to hypothermic ischemia and reperfusion in the neonatal lamb heart.