title: Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure.
abstract: Diabetic patients manifest an increased incidence of heart failure (HF) after myocardial infarction (MI), which presages an increase in morbidity and mortality. Although oxidative stress has been implicated in diabetic complications, oxidative stress status associated with comorbid conditions that frequently accompany diabetes remains unknown. Therefore, we examined antioxidants and oxidative stress in the surviving myocardium in relation to ventricular function during diabetic HF following MI. MI was produced in diabetic and nondiabetic rats by ligation of the left coronary artery. At 4 weeks post-MI, LV systolic pressure (LVSP), rate of pressure rise (+dP/dt), and rate of pressure decay (-dP/dt) were depressed to a significantly greater extent in diabetic compared to nondiabetic MI animals. Higher levels of myocardial 8-isoprostane (8-iso PGF(2alpha)), oxidized glutathione (GSSG), as well as greater upregulation of superoxide dismutase (SOD) and catalase (CAT) protein expression paralleled by increases in enzymatic activity was observed in the diabetic MI animals, indicating higher oxidative stress. These data demonstrate a greater derangement of oxidative stress in the surviving tissues of diabetic post-MI rat hearts concomitant with an increased functional severity of HF, and suggest that chronic antioxidant therapy may be useful for the prophylaxis of subsequent HF after MI associated with diabetes.
authors.affiliation: Department of Biomedical Sciences, Division of Cardiovascular Biology, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd., Nashville, TN 37208, USA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Smith
authors.forename: Milton
authors.initials: M
authors.lastname: Hamblin
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hill
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003925:Diabetic Angiopathies / Q000209:etiology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011506:Proteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D002374:Catalase; D013482:Superoxide Dismutase; D019803:Glutathione Disulfide