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Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest
Published on: August 6, 2015
Role of apoptosis in myocardial stunning after open heart surgery
Joachim P Schmitt1, Josef Schröder, Heribert Schunkert
1Department of Thoracic and Cardiovascular Surgery, University Medical School, Regensburg, Germany. jschmitt@genetics.med.harvard.edu
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.
Insights
Programmed cell death, or apoptosis, is evident after open heart surgery and linked to reduced cardiac function. This study suggests apoptosis plays a key role in myocardial stunning post-surgery.
Area of Science:
- Cardiology
- Cell Biology
- Surgical Research
Background:
- Myocardial preservation during open heart surgery requires understanding postoperative myocardial stunning.
- Investigating the pathophysiologic mechanisms of myocardial stunning is crucial for improving surgical outcomes.
Purpose of the Study:
- To analyze the role of apoptosis in myocardial stunning following open heart surgery.
Main Methods:
- Myocardial samples were collected from 11 patients undergoing coronary artery bypass grafting before and after surgery.
- Apoptosis was assessed using electron microscopy, in situ end-labeling of DNA fragments, and biochemical analysis of mitochondrial cytochrome c release.
Main Results:
- Electron microscopy showed nuclear chromatin condensation and mitochondrial damage in myocytes.
- Increased cytochrome c release (3.4-fold) was observed post-surgery, indicating apoptosis.
- Cytochrome c release correlated negatively with left ventricular function and positively with cardioplegic arrest/reperfusion duration.
Conclusions:
- Programmed cell death (apoptosis) is detectable early after open heart surgery.
- Apoptosis correlates with decreased cardiac contractility.
- Apoptosis is implicated as a significant mechanism in postoperative myocardial stunning.

