Author + information
- Received August 3, 1995
- Revision received October 14, 1995
- Accepted October 27, 1995
- Published online March 15, 1996.
- Shiro Hoshida, MD, PhD∗,
- Masashi Nishida, MD, PhD,
- Nobushige Yamashita, MD,
- Junsuke Igarashi, MD,
- Masatsugu Hori, MD, PhD,
- Takenobu Kamada, MD, PhD,
- Tsunehiko Kuzuya, MD, PhD and
- Michihiko Tada, MD, PhD, FACC
- ↵∗Address for correspondence: Dr. Shiro Hoshida, Division of Cardiology, First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565, Japan.
Objectives. This study compared the effect of a 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 ischemia 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 ischemia (30 min) and reperfusion (48 hr) in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the effect of a nitric oxide donor (S-nitroso-N-acetylpenicillamine [SNAP]), a nitric oxide precursor (l-arginine) or a 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 l-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 a long-term cholesterol-rich diet but was effectively reversed by treatment with a nitric oxide donor. However, this agent did not limit infarct size in normal rabbits. Thus, a nitric oxide donor reduces myocardial infarct size in atherosclerotic but not in nonatherosclerotic rabbits.
☆ This study was supported in part by research grants from the Ministry of Education, Science, and Culture, Tokyo (Drs. Hoshida, Kuzuya and Tada) and by a grant from the Human Frontier Science Project (Dr. Tada), Tokyo, Japan.
- Received August 3, 1995.
- Revision received October 14, 1995.
- Accepted October 27, 1995.