Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion.
METHODS
The purpose of this study was to determine the effects of nitric oxide (NO), believed to be endothelium-derived relaxing factor on reperfusion injury after myocardial ischemia (MI). The effects of NO were investigated in a 6-hr model of MI with reperfusion in open-chest, anesthetized cats. A solution containing NO was infused iv starting 30 min after occlusion of the left anterior descending coronary artery, continuing through reperfusion 1 hr later, and lasting for 5.5 hr. Estimated NO concentration in the circulation was 1 to 2 x 10(-9) M.


RESULTS
The areas-at-risk expressed as a percentage of the total left ventricular weights were not significantly different among either of the MI groups. However, the necrotic area (expressed as a percentage of the myocardial area-at-risk) was significantly (p less than .01) lower in the NO-treated MI cats compared with the MI + vehicle group. Cardiac myeloperoxidase activities indicated that significantly (p less than .05) fewer neutrophils were attracted to the necrotic zone of the NO-treated MI cats when compared with MI cats receiving only the vehicle. Sodium nitrate (NaNO2) (pH 7.4), a major breakdown product of NO, failed to exert any protective effect in this same model of MI and reperfusion.


CONCLUSIONS
NO appears to provide significant myocardial protection after ischemia and reperfusion. NO may afford cardioprotection by incorporation into circulating blood cells (i.e., neutrophils, platelets), thereby inhibiting their accumulation and adherence in the ischemic region, or by a direct cardiac cytoprotective effect. Further studies using NO donors rather than NO would be an appropriate clinically relevant mode of treatment in MI.
Johnson
G
G
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799.
Tsao
P S
PS
Lefer
A M
AM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D012977:Sodium Nitrite / Q000494:pharmacology
D009569:Nitric Oxide; D009195:Peroxidase; D012977:Sodium Nitrite