Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 53, Issue 16, Pages 1425-1436Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2009.01.041
Keywords
apoptosis; glycemic control; inflammation; myocardial infarction; remodeling
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Funding
- Second University of Naples
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Objectives We analyzed the molecular mechanisms evoked by tight glycemic control during post-infarction remodeling in human hearts. Background The molecular mechanisms by which tight glycemic control improves heart remodeling during acute myocardial infarction (AMI) are still largely unknown. Methods Eighty-eight patients with first AMI undergoing coronary bypass surgery were studied: 38 normoglycemic patients served as the control group; hyperglycemic patients (glucose >= 140 mg/dl) were randomized to intensive glycemic control (IGC) (n = 25; glucose 80 to 140 mg/dl) or conventional glycemic control (CGC) (n = 25; glucose 180 to 200 mg/dl) for almost 3 days before surgery, with insulin infusion followed by subcutaneous insulin treatment. Echocardiographic parameters were investigated at admission and after treatment period. During surgery, oxidative stress (nitrotyrosine, superoxide anion [O-2(-)] production, inducible nitric oxide synthase [iNOS]), inflammation (nuclear factor kappa B [NF kappa B], tumor necrosis factor [TNF]-alpha, and apoptosis (caspase-3) were analyzed in biopsy specimens taken from the peri-infarcted area. Results Compared with normoglycemic patients, hyperglycemic patients had higher myocardial performance index (MPI) (p < 0.05), reduced ejection fraction (p < 0.05), more nitrotyrosine, iNOS, and O-2(-) production, more macrophages, T-lymphocytes, and HLA-DR (Dako, Milan, Italy) cells, and more NF kappa B-activity, TNF-alpha, and caspase-3 levels (p < 0.01) in peri-infarcted specimens. After the treatment period, plasma glucose reduction was greater in the IGC than in the CGC group (p < 0.001). Compared with IGC patients, CGC patients had higher MPI (p < 0.02), had lower ejection fraction (p < 0.05), and had more markers of oxidative stress, more inflammation and apoptosis (p < 0.01) in peri-infarcted specimens. Conclusions Tight glycemic control, by reducing oxidative stress and inflammation, might reduce apoptosis in peri-infarcted areas and remodeling in AMI patients. (J Am Coll Cardiol 2009; 53: 1425-36) (C) 2009 by the American College of Cardiology Foundation
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