Background— Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. Methods and Results— Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals ( P <0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine ( P =0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks ( P =0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine ( P =0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment ( P =0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine ( P =0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF ( P =0.002), peNOS (ser1177) ( P =0.04), NFkB ( P =0.004), and pAkt (thr308) ( P =0.001). Conclusions— Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.

This study demonstrates that infusion of H2S is superior to a bolus alone in reducing myocardial necrosis after IR injury, even though some markers of apoptosis and autophagy were affected in both H2S-treated groups. Thus, the current results indicate that infusion of H2S throughout IR may offer better myocardial protection from IR injury.

Background-Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR).We investigate the impact of dietary-induced hypercholesterolemia on the myocardium in the setting of acute IR. Methods and Results-In normocholesterolemic (NC, nϭ7) and hypercholesterolemic (HC, nϭ7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 minutes, followed by reperfusion for 120 minutes. Hemodynamic values were recorded, and TTC staining was used to assess necrosis. Oxidative stress was measured. Specific cell death and survival signaling pathways were assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC versus NC (42% versus 61%, PϽ0.05), whereas the area at risk (AAR) was similar in both groups (Pϭ0.61). Whereas global LV function (ϩdP/dt, PϽ0.05) was higher during entire period of IR in HC versus NC, regional function deteriorated more following reperfusion in HC (PϽ0.05). Ischemia increased indices of myocardial oxidative stress such as protein oxidation (PϽ0.05), lipid peroxidation (PϽ0.05), and nitrotyrosylation in HC versus NC, as well as the expression of phospho-eNOS (PϽ0.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was higher in HC versus NC (all PϽ05). Ischemia caused higher expression of the proapoptotic protein PARP (PϽ0.05), and lower expression of the prosurvival proteins Bcl2 (PϽ0.05), phospho-Akt, (PϽ0.05), and phospho-PKC (PϽ0.05) in the HC versus NC. TUNEL-positive cell count was 3.8-fold (PϽ0.05) higher in the AAR of HC versus NC. Conclusions-This study demonstrates that experimental hypercholesterolemia is associated with increased myocardial oxidative stress and inflammation, attenuation of cell survival pathways, and induction of apoptosis in the ischemic territory, which together may account for the expansion of myocardial necrosis in the setting of acute IR. Key Words: apoptosis Ⅲ hypercholesterolemia Ⅲ ischemia Ⅲ myocardial infarction Ⅲ risk factors C oronary artery disease (CAD) and acute myocardial infarction (AMI) are the largest cause of death in the world today. Prompt reperfusion via angioplasty, thrombolytic therapy, or coronary artery bypass surgery to salvage the ischemic myocardium is considered the optimal management for AMI. 1 In recent years many studies have shown that hypercholesterolemia is not only detrimental for CAD progression but is also a risk factor for higher mortality and poor left ventricular systolic function in patients after AMI. 2,3 This suggests that hypercholesterolemia may adversely influence the evolution of AMI even after patency of an occluded coronary artery is successfully reestablished. However, the mechanisms responsible for enhanced cardiomyocyte injury after ischemia-reperfusion (IR) in patients with hypercholesterolemia are poorly understood.To date, myocardial IR injury studies conducted in hypercholesterolemic animals (rabbits and rodents) have yielded varied and controversial findings. Although some researchers reported that diet-...