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Ann Thorac Surg 1999;67:1689-1695
© 1999 The Society of Thoracic Surgeons
a Departments of Department of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
b Department of Hematology/Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
c Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
Accepted for publication December 18, 1998.
Address reprint requests to Dr Vinten-Johansen, Division of Cardiothoracic Surgery, Department of Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 550 Peachtree St NE, Atlanta, GA 30365-2225
Background. This study tested the hypothesis that ischemic preconditioning (IP) inhibits myocardial apoptosis after a short period of ischemia and reperfusion.
Methods. In 9 anesthetized dogs, the left anterior descending (LAD) coronary artery was occluded for 30 min and reperfused for 3 h (control), while in 9 others, LAD occlusion was preceded by 5 min of occlusion and 5 min of reperfusion (IP). DNA from frozen myocardial tissue samples was extracted, and apoptosis were identified as "ladders" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end-labeling (TUNEL) assay. Neutrophil accumulation was detected by measuring cardiac myeloperoxidase activity.
Results. Thirty minutes of LAD occlusion caused a significant decrease in blood flow (colored microspheres), which was comparable between groups. In the control group, DNA ladders occurred in the area at risk (AAR) in six out nine experiments. In contrast, DNA laddering in the AAR was not observed in any of the IP group. AAR in the control group showed a greater percentage of apoptotic cells than IP (6.7 ± 0.9% vs 1.2 ± 0.2%; p < 0.01). Cardiac myeloperoxidase activity (U/g tissue) was significantly reduced from 0.07 ± 0.004 in control to 0.04 ± 0.01 in IP group (p < 0.05).
Conclusions. We conclude that ischemic preconditioning attenuates apoptosis and neutrophil accumulation in the AAR in a model of nonlethal acute ischemia and reperfusion.
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