The effects of
SP/W-5186, a
cysteine-containing
nitric oxide (.NO) donor, on
myocardial reperfusion injury were studied in a rabbit
ischemia (45 min) and reperfusion (180 min) model. Five min before reperfusion, either low-dose (0.3 micromol/kg) or high-dose (1 micromol/kg)
SP/W-5186 was given intravenously as a bolus. Administration of 0.3 micromol/kg
SP/W-5186 did not change mean arterial blood pressure, heart rate or pressure-rate index. However, administration of low-dose
SP/W-5186 exerted marked cardioprotective effects as evidenced by improved cardiac functional recovery (P <.05 vs. vehicle), decreased plasma
creatine kinase concentration (P <. 01) and reduced
infarct size (P <.01). Moreover, administration of
SP/W-5186 significantly decreased platelet aggregation (P <.01 vs. vehicle), attenuated polymorphonuclear leukocyte (PMN) accumulation in myocardial tissue, inhibited PMN adhesion to endothelial cells and preserved endothelial function. Administration of high-dose
SP/W-5186 resulted in a transient but significant decrease in mean arterial blood pressure and exerted more cardiac protection compared with low-dose treatment. However, the effects on platelet aggregation, PMN accumulation and PMN adhesion did not differ significantly between the two
SP/W-5186 groups. Furthermore, administration of SP/W-6373, an analogue of
SP/W-5186 that lacks the NO moiety, failed to exert any protective effects. These results demonstrate that NO released from
SP/W-5186 significantly protected myocardial tissue from
reperfusion injury. The primary mechanisms of the observed cardioprotection by
SP/W-5186 involve inhibition of platelet aggregation, attenuation of PMN-endothelium interaction and preservation of endothelial function.