Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction.
OBJECTIVE
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.
Shiomi
Tetsuya
T
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan.
Tsutsui
Hiroyuki
H
Ikeuchi
Masaki
M
Matsusaka
Hidenori
H
Hayashidani
Shunji
S
Suematsu
Nobuhiro
N
Wen
Jing
J
Kubota
Toru
T
Takeshita
Akira
A
D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006439:Hemodynamics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D032342:Muscle Cells / Q000473:pathology; D009200:Myocardial Contraction / Q000502:physiology; D009929:Organ Size; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*; D020257:Ventricular Remodeling