Author + information
- Received October 7, 2008
- Revision received January 9, 2009
- Accepted January 19, 2009
- Published online April 21, 2009.
- Raffaele Marfella, MD, PhD*,* (, )
- Clara Di Filippo, PhD†,
- Michele Portoghese, MD§,
- Franca Ferraraccio, MD‡,
- Maria Rosaria Rizzo, MD, PhD*,
- Mario Siniscalchi, MD, PhD∥,
- Emilio Musacchio, MD¶,
- Michele D'Amico, PhD†,
- Francesco Rossi, MD, PhD† and
- Giuseppe Paolisso, MD, PhD*
- ↵*Reprint requests and correspondence:
Dr. Raffaele Marfella, Piazza Miraglia 2, 80138 Napoli, Italy
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 [O2–] production, inducible nitric oxide synthase [iNOS]), inflammation (nuclear factor kappa B [NFκB], tumor necrosis factor [TNF]-α, 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 O2−production, more macrophages, T-lymphocytes, and HLA-DR (Dako, Milan, Italy) cells, and more NFκB-activity, TNF-α, 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.
This study was supported by grants from Second University of Naples.
- Received October 7, 2008.
- Revision received January 9, 2009.
- Accepted January 19, 2009.
- American College of Cardiology Foundation