Introduction Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. Methods The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p < 0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p < 0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.
ObjectivePericardiectomy is associated with a high prevalence of morbidity and mortality. We evaluated the predictors of in-hospital complications and outcome for pericardiectomy procedure for patients with constrictive pericarditis (CP) in a single-center in China.MethodsOne-hundred sixty-five patients who underwent pericardiectomy for CP between January 1990 and December 2012 at our hospital were evaluated.ResultsThe mean age of the study cohort was 36.79 ± 18.52 years. The approach was through a median sternotomy in 91.5% of patients. Cardiopulmonary bypass was used in 14.5% (24/165 patients). Unadjusted rates of mortality and complication were approximately 5.4% and 23%, respectively. The main cause of death was severe low cardiac output syndrome. Major complications were postoperative low cardiac output syndrome, reoperation for bleeding, pneumonia, mediastinitis, chylothorax and cerebral infarction. One-year survival was 92%. One-year follow-up revealed that New York Heart Association functional class III or IV, age, intraoperative use of cardiac pulmonary bypass and hemodialysis were associated with increased mortality and morbidity.ConclusionsTotal pericardiectomy is associated with lower perioperative and late mortality, and the extent of pericardial resection should be decided according to individual conditions. Perioperative management and complete release of the thickened pericardium of the left ventricle should prevent postoperative complications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.