Amelioration of severity of myocardial injury by nitric oxide donor in rabbits fed cholesterol-rich diet

Objectives. This study compared the effect of nitric oxide donor on limiting the size of infarct resulting from myocardial ischemia-reperfusion between atherosclerotic and nonatherosclerotic models. Background. Endothelial-derived relaxation in coronary arteries affected by ischemi is substantially impaired after reperfusion, and this impairment may exacerbate the myocardial ischemia-reperfusion injury. In animals with experimental atherosclerosis, release of endothelial-derived relaxing factor is also decreased, and the propagation of myocardial infarction could be exacerbated. Methods. We examined the extent of myocardial injury induced by ischemi (30 min) and reperfusion (48 hr) in rabbits fed cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the effect of nitric oxide donor (S-nitroso-N-acetylpenicillamine [SNAP]), nitric oxide precursor (image-arginine) or degradation product of SNAP (N-acetylpenicillamine) on infarct size in these models. Results. Severity of myocardial injury was significantly exacerbated in cholesterol-fed rabbits (75.2 ± 4.4% [mean ± SEM]) compared with that in non-cholesterol-fed rabbits (53.2 ± 5.2%). This exacerbation was prevented by treatment with SNAP (50.2 ± 6.4%) but not with image-arginine (70.5 ± 6.0%) or N-acetylpenicillamine (70.4 ± 4.8%) in cholesterol-fed rabbits. However, SNAP did not limit infarct size in non-cholesterol-fed rabbits (60.8 ± 4.2%). The rate-pressure product was similar during the course of the experiment in all the groups. Conclusions. Myocardial damage induced by ischemia-reperfusion was significantly exacerbated in rabbits fed long-term cholesterol-rich diet but was effectively reversed by treatment with nitric oxide donor. However, this agent did not limit infarct size in normal rabbits. Thus, nitric oxide donor reduces myocardial infarct size in atherosclerotic but not in nonatherosclerotic rabbits.