BASIC SCIENCE
Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction
Tetsuya Shiomi, MD*,
Hiroyuki Tsutsui, MD*,*,
Masaki Ikeuchi, MD*,
Hidenori Matsusaka, MD*,
Shunji Hayashidani, MD*,
Nobuhiro Suematsu, MD*,
Jing Wen, MD*,
Toru Kubota, MD* and
Akira Takeshita, MD*
* Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Manuscript received November 11, 2002;
revised manuscript received March 7, 2003,
accepted March 27, 2003.
* Reprint requests and correspondence: Dr. Hiroyuki Tsutsui, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan.
prehiro{at}cardiol.med.kyushu-u.ac.jp
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.
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Abbreviations and Acronyms
| | ACE | | angiotensin-converting enzyme | | CAD | | coronary artery disease | | DM | | diabetes mellitus | | DMTU | | dimethylthiourea | | dP/dt | | rate of rise in left ventricular pressure | | HF | | heart failure | | LV | | left ventricle/ventricular | | MCP | | monocyte chemoattractant protein | | MI | | myocardial infarction | | ROS | | reactive oxygen species | | STZ | | streptozotocin | | TGF | | transforming growth factor | | TNF | | tumor necrosis factor |
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