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Ann Thorac Surg 2002;74:299
© 2002 The Society of Thoracic Surgeons

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Correspondence

Reply

^a Toronto General Hospital, CCRW 1-815, 200 Elizabeth St., Toronto, Ontario M5G 2C4, Canada

e-mail: renkeli{at}uhnres.utoronto.ca

To the Editor

In their letter, Borenstein and coauthors suggest that cell transplantation may represent a novel treatment to improve cardiac function in patients with a dilated cardiomyopathy. However, their results also raise a legitimate concern about cardiac arrhythmias, which can be associated with cell transplantation.

In two previous studies, we [1, 2] implanted 4 x 10⁶ heart cells or smooth muscle cells into the hearts of hamsters with an inherited dilated cardiomyopathy (delta-sarcoglycan gene deficiency). The transplanted cells survived in the diseased myocardium, formed muscle tissue, and prevented or delayed ventricular dilatation compared with medium-injected controls. Scorsin and colleagues [3] demonstrated that transplanted skeletal muscle cells (1 x 10⁶ cells) improved heart function in rats with a doxorubicin-induced dilated cardiomyopathy. In their study, Borenstein and co-workers implanted 50 x 10⁶ satellite cells into the myocardium of dogs with a dilated cardiomyopathy. Although 3 of the 5 animals died early after transplantation, the heart function of the surviving animals improved. The results in both small and large animal models of dilated cardiomyopathy indicate that cell transplantation can prevent or delay ventricular dilatation and improve global heart function for patients with dilated cardiomyopathy.

The mechanism by which implanted cells improve heart function remains controversial. We believe at least three factors directly or indirectly contribute to the structural and functional benefits afforded by muscle cell transplantation. Muscle cell engraftment increases regional elasticity, alters the extracellular matrix to prevent ventricular remodeling, and induces angiogenesis in the failing myocardium.

Borenstein and associates observed intractable tachyarrhythmias in 2 of the 5 dogs. However, no medium-injected control animals were studied. Therefore, it is difficult to know if the arrhythmias were specific to cell transplantation or simply the result of advanced heart failure. The engraftment of muscle cells in an infarcted region could provide a focus for tachyarrhythmia. We have performed heart cell transplantation in a porcine myocardial infarction model and monitored for arrhythmias by cardiac telemetry for 24 hours. We did not identify any arrhythmias up to 4 weeks after transplantation.

Arrhythmia could be dependent on the technique, time, and cell type used. Electrophysiological studies will be required to determine the arrhythmogenic potential of cell transplantation as well as the type and the duration of the arrhythmias, if they occur. Transplant cell-induced arrhythmias are a potential concern for the clinical application of cell transplantation that requires further investigation.

Footnotes

Drs Li, Mickle, and Weisel disclose that they have a financial relationship with Genzyme Corporation.

References

1. Yoo K.J., Li R.-K., Weisel R.D., et al. Heart cell transplantation improves heart function in dilated cardiomyopathic hamsters. Circulation 2000;102(Suppl 3):204-209.
2. Yoo K.-J., Li R.-K., Weisel R.D., Mickle D.A.G., Li G., Yau T.M. Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy. Ann Thorac Surg 2000;70:859-865.[Abstract/Full Text]
3. Scorsin M., Hagege A.A., Dolizy I., et al. Can cellular transplantation improve function in doxorubicin-induced heart failure?. Circulation 1998;98(Suppl 2):151-155.

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Richard D. Weisel Paul W.M. Fedak Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, R.-K. Articles by Mickle, D. A.G. Search for Related Content PubMed PubMed Citation Articles by Li, R.-K. Articles by Mickle, D. A.G. Related Collections Related Articles