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Ann Thorac Surg 2004;77:382
© 2004 The Society of Thoracic Surgeons


Correspondence

Reply

Joachim P. Schmitt, MDa

a Department of Genetics, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA

Hermann Aebert, MDb

b Department of Surgery, Division of Thoracic and Cardiovascular Surgery, Eberhard-Karls-Universität, Tübingen, Germany

e-mail: jschmitt{at}genetics.med.harvard.edu

To the Editor:

Two modes of morphological change have been proposed to describe cell death, from apoptosis to necrosis and from oncosis to necrosis [1]. Whereas apoptosis is associated with nuclear changes such as chromatin condensation and DNA (deoxyribonucleic acid) fragmentation and with the formation of apoptotic bodies, characteristic features of oncosis are disruption of the plasma membrane and cell swelling [1]. These morphological stigmas of oncosis were not observed in our electron microscopy studies of human heart tissue after cardioplegia and reperfusion [2]. To delineate the different pathways of myocyte death, we performed histochemical and biochemical analyses in addition to the histological examinations. The morphological findings in single myocytes surrounded by healthy-appearing cells in concert with positive TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling of fragmented DNA [deoxyribonucleic acid]) staining and characteristic cytochrome c release clearly pointed to early phases of apoptosis rather than oncosis [3].

As discussed in our report [2], the observed citrate synthase release suggests that nonapoptotic cell death also occurred, most likely necrosis after apoptosis. Although our investigations did not show evidence of it, we cannot rule out a contribution of oncosis or necrosis after oncosis. To normalize for this nonapoptotic myocyte death, we calculated the ratio of cytochrome c release and citrate synthase release. This ratio correlated well with the extent of postoperative cardiac dysfunction, a finding suggesting that apoptosis was the major contributor to myocardial stunning.

It is crucial for the clinician to identify and prevent the initiating events that underlie postoperative myocardial stunning, thus improving myocardial protection. According to our data, apoptosis is a major contributor to myocardial stunning early after open heart surgical procedures. It therefore may provide a novel and promising target for therapeutic interventions in the future. The Drs Gorman [4] supported and emphasized our results and conclusions in their invited commentary on our study.

References

  1. Majno G., Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 1995;146:3-15.[Abstract]
  2. Schmitt J.P., Schröder J., Schunkert H., Birnbaum D.E., Aebert H. Role of apoptosis in myocardial stunning after open heart surgery. Ann Thorac Surg 2002;73:1229-1235.[Abstract/Free Full Text]
  3. Green D.R., Reed J.C. Mitochondria and apoptosis. Science 1998;281:1309-1312.[Abstract/Free Full Text]
  4. Gorman R.C., Gorman J.H. Role of apoptosis in myocardial stunning after open heart surgery[]. Ann Thorac Surg 2002;73:1235.[Free Full Text]




This Article
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