Nitric Oxide Attenuates Neutrophil-Mediated Myocardial Contractile Dysfunction After Ischemia and Reperfusion

Abstract With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)–mediated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n=10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n=9), resulted in 80.2±6.7% recovery of LVDP and 77.0±8.6% recovery of PRP. Treatment with l-arginine (2.5 mmol/L, n=10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-l-arginine methyl ester (L-NAME) treatment (250 μmol/L, n=10) resulted ...