Supplementary Material for: Nitric oxide/Glucose transporter type 4 pathway mediates cardioprotection against ischemia/reperfusion injury under hyperglycemic and diabetic conditions in rats

Introduction: The comorbidities of ischemic heart disease (IHD) and diabetes mellitus (DM) compromise the protection of the diabetic heart from ischemia/reperfusion (I/R) injury. We hypothesized that manipulation of reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways might protect the diabetic heart, and intervention of these pathways could be a new avenue for potentially protecting the diabetic heart. Methods: All hearts were subjected to 30 min ischemia and 30 min reperfusion. During reperfusion, hearts were exposed to molecules proven to protect the heart from I/R injury. The hemodynamic data were collected using suitable software. The infarct size, troponin T levels, and protein levels in hearts were evaluated. Results: Both cyclosporine-A and nitric oxide donor (SNAP) infusion at reperfusion protected four-week diabetic hearts from I/R injury. However, six-week diabetic hearts were protected only by SNAP, but not cyclosporin-A. These treatments significantly (P<0.05) improved cardiac hemodynamics and decreased infarct size. Conclusions: The administration of SNAP to diabetic hearts protected both four- and six-week diabetic hearts; however, cyclosporine-A protected only the four-week diabetic hearts. The eNOS/GLUT-4 pathway executed the SNAP-mediated cardioprotection.