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European Journal of Heart Failure 2008 10(1):14-21; doi:10.1016/j.ejheart.2007.11.007
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© 2008 European Society of Cardiology

Preservation of heart function in diabetic rats by the combined effects of muscle cell implantation and insulin therapy

Byung-Ok Kim, Subodh Verma, Richard D. Weisel, Shafie Fazel, Zhi-Qiang Jia, Tomohiro Mizuno and Ren-Ke Li*

Toronto General Research Institute, Division of Cardiovascular Surgery Toronto, Ontario, Canada
Toronto General Hospital, Division of Cardiac Surgery Toronto, Ontario, Canada
University of Toronto Ontario, Canada

* Corresponding author. Toronto General Hospital, MaRS Centre, Toronto Medical Discovery Tower, Room 3-702, 101 College Street, Toronto, ON, Canada M5G 1L7. Tel.: +1 416 581 7492; fax: +1 416 581 7493. E-mail address: renkeli{at}uhnres.utoronto.ca


   Abstract

Background: Diabetic cardiomyopathy is a common cause of heart failure in diabetic patients, but current treatments do not directly improve ventricular function. Cell transplantation can prevent cardiac dilatation after injury, and may also prevent congestive heart failure in diabetic cardiomyopathy.

Aim: This study evaluated the functional effects of smooth muscle cells (SMCs) implanted into the myocardium of insulin- and non insulin-treated diabetic rats.

Methods: Four weeks after streptozotocin infusion, adult Wistar rats were implanted with BrdU-labelled SMCs or culture media (N=12/group). Six rats in each group were also treated with insulin. Echocardiograms were performed at 0, 4 and 8 weeks after streptozotocin injection, and histology and heart function were evaluated at 4 weeks after implantation.

Results: Blood glucose levels decreased after insulin treatment. Among cell-injected rats, histology indicated that those that did not receive insulin retained fewer surviving BrdU+ SMCs, and a smaller volume of myocardial tissue positive for {alpha}smooth muscle actin. Cardiac function was preserved in the insulin-treated groups relative to those that did not receive insulin. Among insulin-treated rats, the cell-injected group functioned better than the media-injected group.

Conclusions: Diabetic cardiomyopathy is partially treatable with insulin; however, a combination of SMC transplantation and insulin treatment produced the best functional result. Cell transplantation may prevent the progression of diabetic cardiomyopathy in patients whose glucose levels are controlled with insulin.

Key Words: Heart failure • Diabetic cardiomyopathy • Heart function • Cell transplantation • Diabetes

Received April 3, 2007; Revised October 12, 2007; Accepted November 6, 2007


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