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J Thorac Cardiovasc Surg 2007;134:1096
© 2007 The American Association for Thoracic Surgery

Letter to the Editor

Reply to the Editor

Department of Surgery and Clinical Science, Yamaguchi University, Graduate School of Medicine, Ube, Yamaguchi, Japan

We greatly appreciate the letter from Stamm and colleagues with its well-directed comments on our article. As they suggest, we need to clarify many problems about hemodynamic unloading for myocardial repair, including "regeneration versus rescue," "acute versus chronic," and "clinical patient versus experimental model."

First, rescue and regeneration are very different biologic processes. The former involves time-limited work to rescue the surviving myocardium soon after damage, whereas the latter is a slow and long-term process of regenerating new myocardium for repairing the injured heart. We recognize that the regenerative potency of the injured heart is poor because of the very limited proliferating potency of cardiomyocytes.¹ Inasmuch as we removed hemodynamic loading soon after infarction in this study, it is possible that hemodynamic unloading rescued much of the surviving myocardium within the injured heart and contributed to the dramatic improvement in the infarcted area and the left ventricular wall thickness, as shown in Figure 1 of our article.² However, the increased number of Ki-67–positive cells indicated an accelerated biologic process of regeneration in the unloading infarcted heart. Furthermore, although we did not follow their fate, the increased number of stem cells in the unloading infarcted heart also played a role in myocardial repair. On the basis of this evidence, we concluded that the reduced hemodynamic loading assists self-regeneration of the injured heart.

Second, compared with the acute phase, the chronically injured heart was characterized by compensatory hypertrophy of the surviving myocardium, the senescence of cardiac stem cells,³ and many other neurohormonal changes. Thus, it is worth investigating whether hemodynamic unloading would assist the regeneration of a chronically injured heart and the capacity and speed of this regeneration.

The final problem relates to the self-regenerative capacity of the injured heart in both patients and experimental animals. In contrast to healthy young animals, many of the patients with heart failure were older and had coexisting systemic diseases, such as diabetes, hyperlipidemia, and hypertension, which contributed to the senescence of stem cells. Naturally, the proliferating potency of cardiomyocytes and the number of cardiac stem cells in older patients with heart failure would be much weaker than those in healthy young animals.⁴

In all, the functional recovery of the failing heart achieved by left ventricular assist device support involves complex mechanisms, which will be affected by many factors.⁵ Although our experimental data suggest that hemodynamic unloading assists self-regeneration of the injured heart, further study is warranted to estimate the functional contribution of myocardial regeneration in patients subjected to left ventricular assist device support.

References

1. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750-1757.[Medline]
   
2. Suzuki R, Li TS, Mikamo A, Takahashi M, Ohshima M, Kubo M, et al. The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment. J Thorac Cardiovasc Surg 2007;133:1051-1058.[Abstract/Free Full Text]
   
3. Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 2005;102:8692-8697.[Abstract/Free Full Text]
   
4. von Harsdorf R, Poole-Wilson PA, Dietz R. Regenerative capacity of the myocardium: implications for treatment of heart failure. Lancet 2004;363:1306-1313.[Medline]
   
5. Wohlschlaeger J, Schmitz KJ, Schmid C, Schmid KW, Keul P, Takeda A, et al. Reverse remodeling following insertion of left ventricular assist devices (LVAD): a review of the morphological and molecular changes. Cardiovasc Res 2005;68:376-386.[Abstract/Free Full Text]
   

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 Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Ryo Suzuki Kimikazu Hamano Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, T.-S. Articles by Hamano, K. Search for Related Content PubMed Articles by Li, T.-S. Articles by Hamano, K. Related Collections Related Article