Ann Thorac Surg 2005;80:2234
© 2005 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Jun Feng, MD, PhD,
Frank W. Sellke, MD
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA02215
(Email: jfeng{at}caregroup.harvard.edu; fsellke{at}caregroup.harvard.edu).
Apoptosis or program cell death has been previously reported to occur during cardioplegic arrest and cardiopulmonary bypass (CPB), suggesting that apoptosis may, at least in part, contribute to myocardial stunning. Vähäsilta and colleagues [1] confirmed these previous findings in their in-vivo pig model and further tested the hypothesis that differences from retrograde and antegrade cardioplegia might translate into differences in appearance of apoptosis. In this interesting and important study, the authors found that retrograde cardioplegia induced higher amount of apoptosis cardiomyocyte death than antegrade cardioplegia. We believe that this is the first report to show that retrograde cardioplegia is inferior to antegrade cardioplegia in inhibiting myocardial apoptosis in both the right and left ventricles. This finding has very important clinical implications because retrograde cardioplegia has been commonly used in the aortic root and aortic valve surgery. These data may partially explain why retrograde cardioplegia is often associated with incomplete perfusion, depressed functional recovery, and impaired preservation of energy metabolism in the right ventricle.
However, there are still several limitations in this study. First, the authors used a relatively short period (30 minutes) of ischemic arrest induced by cold cardioplegia (10°C). They did not measure the myocardial temperature during the 30-minute ischemic arrest. Apoptosis is not only an ischemia-reperfusion event, but also time and temperature dependent. It has been demonstrated that mild or moderate hypothermia protects myocardium against myocardial dysfunction, necrosis, apoptosis, and apoptosis-related gene expression. Second, the authors used cold crystalloid cardioplegia with normothermic (36°C) CPB. In clinical practice, cold crystalloid cardioplegia is often combined with hypothermic CPB to protect ischemic myocardium. Third, the authors used only two histochemical markers to measure apoptosis. TUNEL staining is known to be nonspecific, which has been recently commented by several authors in this journal and others. Measurement of activated caspase-3 with immunohistochemistry was very helpful in this study, but the authors used an unusual and complicated method to quantify activated caspase-3. Western blots for capase-3 cleavage, a pre-requirement for caspase-3 enzymatic activity, poly-(adenosine diphosphate-ribose) polymerase degradation, a major substrate for activated caspase-3, and cytoplasmic cytochrome c releases are excellent methods for detecting myocytes apoptosis. Because different phases of apoptosis may present different "faces of apoptosis," multiple approaches will be very helpful to identify real apoptotic cells.
Irrespective of these limitations, this is an important and relevant study because the changes in apoptosis may not only contribute to short-term functional deterioration, but more important may also contribute to the long-term beneficial effects. Thus, this may affect clinical practice, mainly by the prevention of myocardial apoptosis.
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References
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- Vähäsilta T, Saraste A, Kytö V, et al. Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia Ann Thorac Surg 2005;80:2229-2234.[Abstract/Free Full Text]
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