Abstract P218: Treatment With Nano-polymer Polyethylene-oxide (PEO) Provides Cardioprotection Through eNOS Pathway in a Model of Focal Ischemia-Reperfusion Injury
Medical grade Nano-polymers (NP) are less than 100 nm devoid of toxic effects. NP are used to enhance circulation, drug and gene delivery systems. Injection of some NP increase tissue perfusion and decrease mean blood pressure in animal models. In addition to its rheological effects polyethylene-oxide (PEO) NP have been shown to interact with endothelial cells to increase endothelial nitric oxide(eNO) and its attendant enzyme (eNOS). eNO over expression or induction, has cardioprotective properties in models of myocardial ischemia reperfusion injury (I/R). We hypothesized IV PEO may confer similar cardioprotection in a model of acute myocardial infarction, via induction of eNOS. Male rats (310±9 g, n=16) were randomized to IV injection of 10 ppm of a saline-PEO solution (PEO Tx) or equal volume of saline(CONT). Focal I/R injury was induced by LAD ligation for 30 minutes followed by 120 min of reperfusion. ECG, and aortic pressure monitored continuously and infarct size calculated as % area at risk. eNOS and its active phosphorylated form (p-eNOS) were detected in left ventricle protein extracts using immunoblotting. Mean blood pressure was 78±10 and 75±6 in PEO Tx compared to 58±12 and 66±4 in CONT, at 30 min of Ischemia and 60 min reperfusion respectively (p<0.05 PEO Tx vs CONT). PEO Tx had 28% and 47% higher eNOS and p-eNOS vs. CONT. PEO Tx had a 28% infarct sparing effect compared to CONT. PEO Tx prior to myocardial infarction significantly reduces infarct size and induces activation and up regulation of the well known eNOS pathway, which may in part be one possible mechanism for its observed cardioprotective effect. These preconditioning properties of PEO warrant further investigation.