J Am Coll Cardiol. 2009 Apr 21;53(16):1425-36. doi: 10.1016/j.jacc.2009.01.041.

Tight glycemic control reduces heart inflammation and remodeling during acute myocardial infarction in hyperglycemic patients.

Marfella R¹, Di Filippo C, Portoghese M, Ferraraccio F, Rizzo MR, Siniscalchi M, Musacchio E, D'Amico M, Rossi F, Paolisso G.

Author information

1: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy. raffaele.marfella@unina2.it

Abstract

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 >or=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 [NFkappaB], 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 NFkappaB-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.