NITRIC-OXIDE ATTENUATES NEUTROPHIL-MEDIATED MYOCARDIAL CONTRACTILE DYSFUNCTION AFTER ISCHEMIA AND REPERFUSION

With the knowledge of NO as an antiadhesion molecule, we performed stu dies to investigate the effects of NO on postischemic polymorphonuclea r leukocyte (PMN)-mediated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minu tes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 m illion) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline value s. Infusion of PMNs alone (n=10) led to a 61% reduction in left ventri cular developed pressure (LVDP) and a 57% reduction in the pressure-ra te product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor , GAS-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) resu lted in a similar improvement in the postischemic contractile state of the heart. In contrast, N-G-nitro-L-arginine methyl ester (L-NAME) tr eatment (250 mu mol/L, n=10) resulted in an exacerbation of contractil e dysfunction, as evidenced by a 93% reduction in LVDP at 45 minutes o f reperfusion and a 91% reduction in PRP. The deleterious effects of L -NAME were prevented by L-arginine coperfusion. We failed to observe a ny cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusi on in the absence of PMNs. In conclusion, PMN-mediated myocardial cont ractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.