Abstract 17400: Charge-Stabilized Nanostructures Reduce Ischemia-Reperfusion Injury in A Pig Model in vivo
Background: Inflammation contributes to reperfusion injury, and experimental studies employing anti-inflammatory treatments have shown beneficial effects. RNS60 is a 0.9% NaCl solution containing charged-stabilized nanostructures as a result of mechanical processing in the presence of oxygen. Preclinical in-vitro and in-vivo studies in multiple disease models have demonstrated that RNS60 modulates ion channels and has broad anti-inflammatory and cytoprotective effects.
Objective: To test the hypothesis that RNS60 will positively influence survival and physiological parameters after myocardial infarction, we conducted a study in the balloon-induced myocardial ischemia/reperfusion (I/R) model in pigs.
Methods: Male and female domestic pigs (45-50 kg) were subjected to myocardial ischemia by occlusion of the left anterior descending coronary artery for 40 minutes. Groups of males or females (n = 4/group) were treated with RNS60 or normal saline (NS) as control by single intracoronary injection (0.065 mL/kg) at time of reperfusion and by subsequent intravenous injections (100 mL/kg) every 4 hours for 7 days. ECGs were analyzed for T-wave abnormalities including T-elevation, biphasic T-waves and flipped T-waves. Myocardial damage was assessed by measuring circulating levels of troponin and by histologic analysis of the left ventricle for signs of tissue necrosis and inflammatory cell infiltration.
Results: RNS60 treatment reduced mortality in male pigs (0/4 in RNS60 group vs. 2/4 in NS group) and caused a normalization of ECG tracings both in males and in females. In addition, RNS60 treatment completely prevented the infarct-induced elevation of circulating levels of cardiac troponin in male pigs at 6 (RNS60 1.12±0.36 vs. NS 6.00±3.39 ng/mL), 12 (RNS60 0.71±0.16 vs. NS 16.96±11.05 ng/mL), and 24 hours (RNS60 0.46±0.17 vs. NS 16.41±12.75 ng/mL). Consistent with these findings, the hearts of RNS60-treated male pigs were free of signs of necrosis or mononuclear infiltration at 7 days post I/R.
Conclusion: Treatment with a saline solution containing CSNs has the potential to reduce I/R injury in vivo.
- © 2011 by American Heart Association, Inc.