EFFECT OF L-ARGININE CARDIOPLEGIA ON RECOVERY OF NEONATAL LAMB HEARTSAFTER 2 HOURS OF COLD ISCHEMIA

Background. Despite hypothermia and cardioplegia, myocardial ischemia followed by reperfusion results in both ventricular and endothelial dy sfunction. The endothelial dysfunction is characterized by a reduced r esponse to acetylcholine, which implies a reduced ability of the endot helium to release nitric oxide after hypothermic ischemia and reperfus ion. We have previously demonstrated that infusion of the nitric oxide precursor L-arginine only during reperfusion after hypothermic ischem ia significantly improves the recovery of ventricular function and res ults in an increased vasodilator response to the infusion of acetylcho line. In contrast, other investigators have found that nitric oxide ha s 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 cardiople gia 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. Con trols received only cardioplegia (dextrose-potassium). Results. At 30 minutes of reperfusion, the L-arginine group showed a significantly im proved recovery in left ventricular systolic function (maximum develop ed pressure, developed pressure at a constant balloon volume [V10] res ulting in an end-diastolic pressure of 10 mm Hg before ischemia, posit ive maximum dP/dt, and dP/dt at V10), diastolic function (negative max imum dP/dt and end-diastolic pressure at V10), coronary blood now, end othelial function (assessed by the coronary vascular resistance respon se 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 grou ps. Conclusions. These results suggest that provision of more substrat e for the endothelial production of nitric oxide during ischemia has a n important salutary effect on the recovery of postischemic myocardial and endothelial function and provide further evidence for an importan t role for the endothelial production of nitric oxide in the response to hypothermic ischemia and reperfusion in the neonatal lamb heart.