Role of apoptosis in myocardial stunning after open heart surgery

Background. Myocardial preservation during open heart surgery is a subject of intense investigation. A prerequisite for further improvement is a better understanding of the underlying pathophysiologic mechanisms responsible for postoperative myocardial stunning. In this report, we analyzed the role of apoptosis in myocardial stunning. Methods. Myocardial samples were obtained from 11 patients undergoing elective coronary artery bypass grafting before (control) and after cardioplegic arrest and reperfusion. Specimens were examined for apoptosis by electron microscopy, in situ end-labeling of DNA fragments, and biochemically for mitochondrial cytochrome c release. Results. Electron microscopy revealed condensation and margination of nuclear chromatin after surgery, as well as swelling and membrane rupture in mitochondria of single myocytes surrounded by healthy cells. TUNEL-positive cells were also found. Cytochrome c release, an initial step in apoptosis, revealed a 3.4 +/- 0.4-fold increase during surgery (p < 0.0001). Furthermore, cytochrome c release from otherwise intact mitochondria showed a negative correlation with left ventricular function and a positive correlation with the duration of cardioplegic arrest and reperfusion (p < 0.05). Conclusions. Our data demonstrate that programmed cell death is evident early after open heart surgery and correlates with declining cardiac contractility. We conclude that apoptosis may be an important mechanism in postoperative myocardial stunning.