Resveratrol regulates autophagy signaling in chronically ischemic myocardium

ObjectiveAutophagy is a cellular process by which damaged components are removed. Although autophagy can result in cell death, when optimally regulated, it might be cardioprotective. Resveratrol is a naturally occurring polyphenol also believed to be cardioprotective. Using a clinically relevant swine model of metabolic syndrome, we investigated the effects of resveratrol on autophagy in the chronically ischemic myocardium.MethodsYorkshire swine were fed a regular diet (n = 7), a high cholesterol diet (n = 7), or a high cholesterol diet with supplemental resveratrol (n = 6). After 4 weeks, an ameroid constrictor was surgically placed on the left circumflex artery to induce chronic myocardial ischemia. The diets were continued another 7 weeks, and then the ischemic and nonischemic myocardium were harvested for protein analysis.ResultsIn the ischemic myocardium, a high cholesterol diet partly attenuated the autophagy, as determined by an increase in phosphorylated mammalian target of rapamycin (p-mTOR) and a decrease in p70 S6 kinase (P70S6K), lysosome-associated membrane protein (LAMP)-2, and autophagy-related gene 12-5 conjugate (ATG 12-5; P < .05). The addition of resveratrol blunted many of these changes, because the p-mTOR, P70S6K, and LAMP-2 levels were not significantly altered from those of the pigs fed a regular diet. Other autophagy markers were increased with a high cholesterol diet, including light chain 3A-II and beclin 1 (P < .05). In the nonischemic myocardium, beclin 1 was decreased in the high cholesterol-fed pigs (P < .05); otherwise no significant changes in protein expression were noted among the 3 groups.ConclusionsIn the chronically ischemic myocardium, resveratrol partly reversed the effects of a high cholesterol diet on autophagy. This might be a mechanism by which resveratrol exerts its cardioprotective effects

Effects of gender and ethnicity on outcomes after aortic valve replacement

ObjectiveTo evaluate the clinical outcomes after aortic valve replacement or aortic valve replacement and coronary artery bypass grafting in a large contemporary population, and to determine if outcomes are associated with patient ethnicity and gender status.MethodsUsing the Massachusetts Cardiac Surgery Database, we identified 6809 adults aged 18 years or older who had undergone isolated aortic valve replacement or aortic valve replacement and coronary artery bypass grafting in all non-federal acute-care Massachusetts hospitals from 2002 to 2008. Univariate and multivariate logistic regression analyses were used to identify differences in patient characteristics, major morbidity, and 30-day and 1-year mortality between men (n = 4043) and women (n = 2766) and between whites (n = 6481) and nonwhites (n = 328).ResultsThe unadjusted 30-day mortality rate was 2.6% for the men and 3.1% for the women (P = .296) and 2.8% for whites and 3.7% for nonwhites (P = .342). In adjusted logistic regression models, the 30-day mortality was not different between the female and male patients (odds ratio, 0.88; 95% confidence interval, 0.26–3.02, P = .84) nor between the nonwhites and whites (odds ratio, 1.57; 95% confidence interval, 0.45–5.44; P = .48). The incidence of postoperative stroke was greater in women (3.0% women and 2.2% men, P = .031), and the incidence of postoperative myocardial infarction (10.9% women and 13.6% men; P = .001) and septicemia (1.2% women and 2.0% men; P = .009) was greater in men.ConclusionsEthnicity and gender were not associated with greater 30-day and 1-year mortality after aortic valve replacement or aortic valve replacement and coronary artery bypass grafting. Differences in postoperative outcomes were not observed between ethnic groups

Hypercholesterolemia and chronic ischemia alter myocardial responses to selective cyclooxygenase-2 inhibition

ObjectiveCyclooxygenase-2 inhibitors have been implicated in adverse cardiac events. We hypothesize that hypercholesterolemia and ischemia may alter the myocardial response to the cyclooxygenase-2 inhibitor celecoxib.MethodsYorkshire swine fed normal chow (CX, n = 6) or high-cholesterol diet (HCX, n = 6) underwent placement of an Ameroid constrictor on the left circumflex artery and were started on celecoxib (200 mg/day). After 7 weeks, ischemic and nonischemic myocardium was analyzed for thrombogenic ratio (thromboxane content divided by prostacyclin content), total protein oxidative stress, and expression of prostacyclin synthase, thromboxane synthase, myeloperoxidase, and superoxide dismutase. Cardiac function, tissue perfusion, and vessel density were measured.ResultsHCX animals were significantly hypercholesterolemic compared with CX animals. Thrombogenic ratio was significantly higher in the HCX group than in the CX group, but prostacyclin and thromboxane synthase expression was similar in all tissues. Myocardial perfusion was decreased in the HCX group compared with the CX group. Total oxidative stress, myeloperoxidase, and superoxide dismutase were increased in ischemic tissue compared with nonischemic tissues, but there was no diet-induced difference between groups. There was no difference in capillary or arteriolar density between groups. Left ventricular contractility was greater in the HCX group than in the CX group, but there was no significant difference in heart rate, mean arterial pressure, or left ventricular pressure.ConclusionsHypercholesterolemic patients using celecoxib may be at higher risk for thrombotic events than those with normal cholesterol, but the relationship between dyslipidemia, ischemia, and cyclooxygenase-2 inhibition is likely much more complicated than originally thought

Potential of vascular endothelial growth factor as a biomarker of coronary artery disease in subjects undergoing CABG surgery

Introduction: • Coronary artery disease (CAD) causes local hypoxia due to reduced blood flow • Hypoxic conditions are known to induce vascular endothelial growth factor (VEGF) production, a key contributor to angiogenesis • The purpose of this study was to determine the potential of VEGF as a marker of myocardial stress in subjects with CAD undergoing coronary artery bypass grafting (CABG) surger