Abstract 354: Nitrate Improves Postresuscitation Myocardial Dysfunction by Preserving Myocardial Nitric Oxide and Phospholamban Protein

Abstract

Objectives: Sarcoplasmic reticulum (SR) Ca 2+ handling proteins have been shown to play an important role in myocardial dysfunction after acute ischemic/reperfusion injury. We assessed the hypothesis that nitrite would improve postresuscitation myocardial dysfunction by increasing NO generation, and the mechanism is related to the modulation of SR Ca 2+ handling proteins. Methods: We performed a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 μg/g). Nitrite (1.2nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in sham group. Hemodynamic parameters were monitored invasively for one hour after ROSC. Echocardiogram was performed to evaluate cardiac function. Myocardial sample was harvested 5 minutes and 1 hour after ROSC respectively. The expression of sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a), phospholamban (PLB) and rynodine receptors (RyRs) were analyzed by Western blot analysis. Myocardial NO five minutes after ROSC were measured using Nitric Oxide Assay Kit. Results: Myocardial function measured as the maximal rate of LV pressure increase (dP/dtmax), the maximal rate of LV pressure decline (-dP/dtmax), ejection fraction, fractional shortening was significantly impaired in nitrite and placebo groups after resuscitation, and cardiac function in nitrite group was significantly greater than placebo group. Nitrite administration increased the level of nitric oxide in myocardium 5 min after resuscitation when compared to the other two groups. The levels of phosphorylated phospholamban were decreased after resuscitation, and nitrite preserved the phosphorylation of phospholamban in myocardium after resuscitation when compared to placebo group. No significant differences were found in the expressions of myocardial sarcoplasmic reticulum Ca 2+ ATPase and rynodine receptors after resuscitation. Conclusions: Nitrite administered during resuscitation improves postresusctation myocardial dysfunction as an exogenous donor of nitric oxide, and the modulation of phosphorylated phospholamban, an important SR Ca 2+ uptake protein, is involved in the mechanism.