Overexpression of copper/zinc superoxide dismutase (SOD1) in the median preoptic nucleus improves cardiac function after myocardial infarction in the rat (686.17)

Previous reports indicate that overexpression of SOD1, an intracellular superoxide (O 2 •‐ ) scavenging enzyme, in the brain subfornical organ improves cardiac function in a mouse model of heart failure (HF). A downstream hypothalamic site, the MnPO, may act as a relay center for O 2 •‐ to act as a mediator in the pathophysiology of HF. To test the hypothesis that elevated O 2 •‐ in the MnPO contributes to the pathophysiology of HF and decreased cardiac function, we injected adenovirus encoding SOD1 (AdSOD1, n=4) or control empty vector (AdE, n=4) into the MnPO of normal rats. Subsequently, rats were subjected to coronary artery ligation to create a myocardial infarct (MI) of the left ventricle. Cardiac function was monitored at 2 week intervals via echocardiography. Upon completion, rat brains were examined for SOD1 expression in MnPO via immunofluorescence and histopathological analyses of cardiac infarct size were conducted. Baseline (EF) ejection fractions (%) of AdSOD1 and AdE rats were 69±2 and 72±3, respectively. One week after MI, EF was significantly decreased in both groups of rats (AdSOD1: 44±5, AdE: 49±2). In contrast by 5 weeks post MI, EF had improved to 55±3 in AdSOD1 rats yet was only 42±4 in AdE rats. In conclusion, despite decreases in EF early after MI, overexpression of SOD1 in the MnPO was related to an improvement in left ventricular function 5 weeks post MI.