Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis.
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.
Wang
N P
NP
Department of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia 30365-2225, USA.
Bufkin
B L
BL
Nakamura
M
M
Zhao
Z Q
ZQ
Wilcox
J N
JN
Hewan-Lowe
K O
KO
Guyton
R A
RA
Vinten-Johansen
J
J
D000818:Animals; D017209:Apoptosis; D004285:Dogs; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D020287:In Situ Nick-End Labeling; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism
D009195:Peroxidase