Abstract 18980: Cardioprotective Role of NO Derived from Sodium Nitrite in Attenuating Severity of Chronic Ischemia-Induced Heart Failure
Background: Nitric oxide (NO) bioavailability is reduced in the setting of congestive heart failure. Nitrite (NO2) is a critically important NO intermediate that is readily metabolized to NO during ischemic conditions. We have previously demonstrated that NO2- ameliorates acute myocardial ischemia/reperfusion (MI/R). However, no evidence exists as to whether increasing NO bioavailability through NO2- therapy attenuates chronic heart failure following acute myocardial infarction.
Methods: Male C57/BL6J Mice (n=13-15 per group) at 12-14 weeks of age underwent 60 min. of myocardial ischemia (MI) induced by transient LCA occlusion followed by 4 weeks of reperfusion. Sodium nitrite (NaNO2) or saline vehicle (VEH) was administered at a dose of 165 µg/kg (intracardiac injection) at reperfusion and then daily for 4 weeks in the drinking water (50 mg/L or 100 mg/L). Two-dimensional echocardiography was performed at baseline and 4 weeks post MI to assess left ventricular (LV) dimensions and ejection fraction (EF). Myocardial and blood NO metabolite levels were measured using HPLC and chemiluminescence methods.
Results: Both circulating and cardiac NaNO2 levels were increased in mice treated with oral NaNO2. Furthermore, NaNO2 (100 mg/L) significantly preserved LVEF (47 ± 4% vs. 32 ± 4%, p < 0.01) and improved left ventricular LV dimensions (LVEDD/LVESD; 4.0/3.1 mm vs. 4.5/3.9 mm, p<0.05) at 4 weeks when compared to VEH.
Conclusions: These data demonstrate that sodium nitrite therapy significantly improves LV function during heart failure following acute myocardial infarction. Studies are currently underway to define the cellular and molecular mechanisms by which NO derived from NaNO2 protects the myocardium in the setting of heart failure.
- © 2012 by American Heart Association, Inc.