Amelioration of severity of myocardial injury by a nitric oxide donor in rabbits fed a cholesterol-rich diet.
OBJECTIVE
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.
Hoshida
S
S
Division of Cardiology, First Department of Medicine, Osaka University School of Medicine, Japan.
Nishida
M
M
Yamashita
N
N
Igarashi
J
J
Hori
M
M
Kamada
T
T
Kuzuya
T
T
Tada
M
M
D000704:Analysis of Variance; D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000150:complications; D007962:Leukocytes / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology*
D002791:Cholesterol, Dietary; D014665:Vasodilator Agents; D007975:Leukotriene B4; D009569:Nitric Oxide; C010005:N-acetylpenicillamine; D026423:S-Nitroso-N-Acetylpenicillamine; D009195:Peroxidase; D010396:Penicillamine