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

Tetsuya Shiomi, Hiroyuki Tsutsui, Masaki Ikeuchi, Hidenori Matsusaka, Shunji Hayashidani, Nobuhiro Suematsu, Jing Wen, Toru Kubota, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalJournal of the American College of Cardiology
Volume42
Issue number1
DOIs
Publication statusPublished - Jul 2 2003

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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