Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction

J Am Coll Cardiol. 2003 Jul 2;42(1):165-72. doi: 10.1016/s0735-1097(03)00509-6.

Abstract

Objectives: The aim of the present study was to determine whether streptozotocin (STZ)-induced hyperglycemia exacerbates progressive left ventricular (LV) dilation and dysfunction after myocardial infarction (MI).

Background: Diabetes mellitus (DM) adversely affects the outcomes in patients with MI. However, it is unknown whether DM can directly affect the development of post-MI LV remodeling and failure.

Methods: Male mice were injected intraperitoneally with STZ (200 mg/kg; DM group) or vehicle only. At two weeks, MI was created in the STZ-injected (DM+MI group) or vehicle-injected mice (MI group) by left coronary artery ligation, and they were followed up for another four weeks.

Results: Survival during six weeks was significantly lower in the DM+MI versus MI group (25% vs. 71%; p < 0.01), despite a similar infarct size (60 +/- 2% vs. 61 +/- 2%; p = NS). Echocardiography after two weeks of ligation showed LV dilation and dysfunction with MI, both of which were exaggerated in the DM+MI group. Likewise, LV end-diastolic pressure and lung weight were increased in mice with MI, and this increase was enhanced in the DM+MI group. The myocyte cross-sectional area in the non-infarcted LV increased to a similar degree in the DM+MI and MI groups, whereas the collagen volume fraction was greater in the DM+MI group. Deoxyribonucleic acid laddering was greater in the DM+MI group.

Conclusions: Hyperglycemia decreased survival and exaggerated LV remodeling and failure after MI by increasing interstitial fibrosis and myocyte apoptosis. Diabetes mellitus could be a risk factor for heart failure, independent of coronary artery lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Hemodynamics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Muscle Cells / pathology
  • Myocardial Contraction / physiology
  • Organ Size
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Remodeling*