Synergism between superoxide dismutase and sodium nitrite in cardioprotection following ischemia and reperfusion.
The effects of acidified sodium nitrite (NaNO2), a releaser of nitric oxide (NO), combined with human superoxide dismutase (hSOD), were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5 mmol/kg/hr) was infused intravenously in cats starting 0.5 hour after occlusion of the left anterior descending (LAD) coronary artery, which was reperfused 1.5 hour following occlusion. Significantly lower plasma creatine phosphokinase activities were observed at all times beyond 3 hours for MI cats given NaNO2 + hSOD when compared with the other MI groups. The areas-at-risk expressed as percentages of the total left ventricular weights were not significantly different among any of the MI groups. However, the necrotic area expressed as a percentage of the myocardial area-at-risk was significantly lower in the MI + NaNO2 + hSOD-treated cats compared with all other MI groups. The NaNO2-treated group also produced a significant decrease in the necrotic area relative to the area-at-risk. Cardiac myeloperoxidase (MPO) activities indicated no significant difference in number of neutrophils attracted to the ischemic zone in the NaNO2 + hSOD-treated MI cats when compared with the other MI groups. Acidified NaNO2 + hSOD together exert significant protection on the myocardium subjected to ischemia and reperfusion injury. NaNO2 may act synergistically with hSOD to prolong the action of NO by scavenging free radicals that inactivate NO.
Johnson
G
G
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Tsao
P
P
Lefer
A M
AM
D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy; D003402:Creatine Kinase / Q000097:blood; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000201:enzymology; D009573:Nitrites / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D012977:Sodium Nitrite / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D009573:Nitrites; D009195:Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D012977:Sodium Nitrite