Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion.
The effects of acidified sodium nitrite (NaNO2) which releases nitric oxide, a substance which is thought to be indistinguishable from endothelium-derived relaxing factor, were investigated in a 6-h model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5-50 mmol/kg/hr) was infused i.v., starting 30 min postocclusion followed by reperfusion 1 hr later, in cats subjected to MI by occlusion of the left anterior descending coronary artery. Acidified NaNO2 infusion (25 and 50 mmol/kg/hr) resulted in significantly lower plasma creatine kinase activities at every time beyond 1 hr for the MI + vehicle group, and was not significantly different when compared to sham MI + NaNO2 controls. The areas at risk expressed as percentage of the total left ventricular weights were not significantly different between the MI + vehicle and MI + acidified NaNO2 groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the 25 and 50 mmol/kg/hr NaNO2-treated cats. Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the ischemic zone of the NaNO2-treated MI cats when compared to the vehicle-infused MI cats. Acidified NaNO2 significantly inhibited platelet aggregation in a dose-dependent manner in cat platelet-rich plasma. Thus, acidified NaNO2 exerts a significant protective action during ischemia and reperfusion injury, which suggests that endothelium-derived relaxing factor has a cardioprotective effect in MI.
Johnson
G
G
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Tsao
P S
PS
Mulloy
D
D
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003327:Coronary Disease / Q000201:enzymology / Q000503:physiopathology*; D003402:Creatine Kinase / Q000097:blood; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009573:Nitrites / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D012977:Sodium Nitrite / Q000494:pharmacology*
D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D009195:Peroxidase; D003402:Creatine Kinase; D012977:Sodium Nitrite