Supplement of nitric oxide attenuates neutrophil-mediated reperfusion injury

Nitric oxide (NO) derived from the endothelial cell has been identified as a constitutive chemical mediator that regulates the function of the endothelial cell in association with neutrophil (PMN) adhesion and activation. However, its role in the pathogenesis of myocardial reperfusion injury is not clear.

Fifteen isolated rat hearts were perfused with modified Krebs-Henseleit solution and subjected to 20 minutes of global and normothermic ischemia. Then the hearts were reperfused for 45 minutes with different protocols: the control (C) group was reperfused without PMNs, the P group was reperfused with PMNs, and the N group was reperfused with PMNs and nitroprusside (10(-5) mol/L). The ozone chemiluminescence method was used for direct measurement of NO in the coronary effluent during reperfusion. NO in the coronary effluent in the C group decreased at reperfusion after normoxic perfusion, and this decrease in NO continued for the first 15 minutes of reperfusion. Percentage recovery of left ventricular developed pressure and coronary flow was significantly lower in the P group than that in the N group. Also, the N group had a significantly lesser Luminol-elicited chemiluminescence of the coronary effluent and ratio of PMN adherence to myocardial vasculature compared with the P group.

This study demonstrated directly the decrease in NO production during reperfusion and showed that supplement of NO with NO donor attenuated the injury in which PMNs were involved. The results suggest that NO plays a significant role in reperfusion injury and that supplement of NO during reperfusion appears to be useful to attenuate this injury.