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Ann Thorac Surg 2003;76:2061
© 2003 The Society of Thoracic Surgeons

Invited commentary

Department of Congenital Heart Disease/Pediatric Cardiology, Albert Ludwings University of Freiburg, Mathildenstrasse 1, D-79106 Freiburg, Germany

e-mail: dittrich{at}kikli.ukl.uni-freiburg.de

Doctor Yarbrough and colleagues address the point of intracellular calcium overload as one possible explanation for the deleterious effects of reperfusion. While MCC-135 has been shown to enhance calcium reuptake into and to reduce calcium leakage from the sarcoplasmatic reticulum in isolated fibers of failing diabetic rat hearts, the new information from its use in the acute ischemic porcine model is improved regional wall motion and relaxation in the reperfused area, associated with a decreased heart rate.

Their experiment in this paper can certainly broaden our knowledge in two directions: (1) by deepening our understanding of the pathophysiology involved in acute ischemic/reperfusion damage, and (2) it proposes a therapeutic means of lessening reperfusion damage. However, there is still a great deal of further investigation necessary to answer the many questions arising from this study. The molecular mechanism that leads to decreased sarcoplasmatic reticulum calcium uptake in failing hearts is not completely understood. That raises the question: in which cells within the postischemic area, and with which molecular mechanisms is the positive MCC-135 effect developed? Their study provides a very clear indication that the timing of pharmacological intervention is crucial. But how is the calcium reuptake induced, and during which harmful stage do myocytes profit from it? Is the reduced heart rate observed in his model really indicative of lowered cardiac oxygen demand? The primary therapeutic goal after an ischemic event is the survival of as many cells with borderline damage as possible. This is an important study, but concerning the question if the use of MCC-135 reduces the rate of apoptosis and cell degeneration in ischemic border areas, the authors have shown a tendency to extrapolate perhaps a bit too far, given the evidence they provide with the observations of various CK-MB and troponin-I profiles.

Many questions remain on the therapeutic front as well, concerning the relationship between MCC-135's dosage and effect, and its side effects regarding the sinus node and vascular system in particular. This is of special importance, as the authors have emphasized their model's potential within the clinical setting. However, this study has not demonstrated that the improvement of regional wall motion leads to better global function. Further investigations of the authors' hypotheses originating from this study will clarify the significance of calcium metabolism, and promise new horizons in the understanding and treatment of myocardial ischemia/reperfusion injury.

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 Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dittrich, S. Search for Related Content PubMed Articles by Dittrich, S. Related Collections Myocardial protection