Additive effects of L-arginine infusion and leukocyte depletion on recovery after hypothermic ischemia in neonatal lamb hearts.

Prior experiments on hypothermic ischemia/reperfusion have shown that (1) leukocytes have an important role in the injury resulting from hypothermic ischemia/reperfusion and (2) endothelial dysfunction with reduced release of nitric oxide occurs after hypothermic ischemia/reperfusion. L-Arginine is a nitric oxide precursor, and the effects of nitric oxide released from endothelial cells include vasorelaxation and inhibition of leukocyte adhesion to endothelium. The potential roles of an interaction between endothelial dysfunction and leukocyte-mediated injury were examined in neonatal hearts. Thirty-two isolated, blood-perfused neonatal lamb hearts were subjected to 2 hours of 10 degrees C cardioplegic ischemia. Group L-arginine received a 3 mmol/L dose of L-arginine during the first 20 minutes of reperfusion. In group leukocyte depletion, leukocytes were depleted (Sepacell filter) from the perfusate before reperfusion. In group L-arginine+leukocyte depletion, leukocytes were depleted and a 3 mmol/L dose of L-arginine was infused during early reperfusion. The control group had no intervention during reperfusion. At 30 minutes of reperfusion, left ventricular maximum developed pressure, positive maximum and negative maximum first derivative of left ventricular pressure (dP/dt), developed pressure at V10 (volume that produces a left ventricular endiastolic pressure of 10 mm Hg at baseline measurement), and dP/dt at V10 were measured. Coronary blood flow was continuously monitored and oxygen consumption was also measured to evaluate the metabolic recovery. In each heart, we also tested coronary vascular resistance response to the endothelium-dependent vasodilator acetylcholine 10(-7) mol/L and the endothelium-independent vasodilator trinitroglycerin 3 x 10(-5) mol/L to assess endothelial function. Results are given as mean percent recovery of baseline values +/- standard deviation. Group L-arginine+leukocyte depletion showed significantly greater recovery of left ventricular function than the other three groups, and groups L-arginine and leukocyte depletion also showed better recovery than the control group (positive maximum dP/dt: control group = 68.3% +/- 8.8%, group L-arginine = 88.8% +/- 3.8%, group L-arginine+leukocyte+leukocyte depletion = 100.6% +/- 8.7%, group leukocyte depletion = 79.3% +/- 8.1%; p < 0.05). Groups L-arginine and L-arginine+leukocyte depletion had higher postischemic coronary blood flow than other groups (control group = 133.0% +/- 31.6%, group L-arginine = 203.2% +/- 32.1%, group L-arginine+leukocyte depletion = 222.0% +/- 30.4%, group leukocyte depletion = 156.3% +/- 29.0%; p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)