CLINICAL RESEARCH: CORONARY ARTERY DISEASE
Tight Glycemic Control Reduces Heart Inflammation and Remodeling During Acute Myocardial Infarction in Hyperglycemic Patients
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*
* Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy
Department of Experimental Medicine, Second University of Naples, Naples, Italy
Department of Clinical, Public, and Preventive Medicine, Second University of Naples, Naples, Italy
Cardiovascular Surgery Unit, Sassari Hospital, Sassari, Italy
|| Intensive Coronary Unit, Hospital Agropoli, Agropoli, Italy
¶ Intensive Coronary Unit, Hospital Cardarelli, Campobasso, Italy
Manuscript received October 7, 2008;
revised manuscript received January 9, 2009,
accepted January 19, 2009.
* Reprint requests and correspondence: Dr. Raffaele Marfella, Piazza Miraglia 2, 80138 Napoli, Italy (Email: raffaele.marfella{at}unina2.it).
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 [NF B], tumor necrosis factor [TNF]- , 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 NFB-activity, TNF-, 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.
Key Words: apoptosis • glycemic control • inflammation • myocardial infarction • remodeling
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Abbreviations and Acronyms
| | AMI = acute myocardial infarction | | CABG = coronary artery bypass graft surgery | | CGC = conventional glucose control | | ET = ejection time | | IGC = intensive glucose control | | iNOS = inducible nitric oxide synthase | | IRT = isovolumetric relaxation time | | MPI = myocardial performance index | | NFB = nuclear factor kappa B | | NSTEMI = non–ST-segment elevation myocardial infarction | | O2
–
= superoxide anion | | STEMI = ST-segment elevation myocardial infarction | | TNF = tumor necrosis factor |
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