Apoptosis in ischemic and reperfused rat myocardium.
Apoptosis has been observed previously in hearts subjected to either continuous ischemia or ischemia followed by reperfusion. The purpose of this study was to compare the timing and extent of apoptosis in both continuously ischemic and reperfused myocardium. We show that rats subjected to continuous coronary artery occlusion display characteristic signs of apoptosis solely in the ischemic myocardium after only 2.25 hours of ischemia, as illustrated by positive in situ end labeling (ISEL) of apoptotic cardiomyocyte nuclei in tissue sections and/or the presence of DNA "ladders" in agarose gels. In contrast, reperfusion after a 45-minute occlusion accelerated the process, with apoptosis becoming evident solely in the reperfused myocardium after only 1 hour of reperfusion. ISEL and DNA ladder intensity increased with duration of ischemia or reperfusion. The volume of myocardium in which ISEL was observed was smaller in the reperfused hearts, and the ISEL-stained nuclei represented 23% and 33% of the total nuclei in the reperfused and permanently occluded myocardium, respectively. Therefore, the data suggest that reperfusion lowers the extent of apoptosis in ischemic myocardium but, paradoxically, accelerates the residual apoptosis, possibly because of reperfusion injury. A large accumulation of neutrophils was observed in both the permanently occluded and reperfused myocardium, suggesting that the inflammatory response may have contributed to apoptosis in both settings. This study therefore confirms that both ischemic and reperfused rat myocardium can undergo apoptotic cell death. However, the data suggest that although reperfusion lowers the number of myocytes undergoing apoptosis, it accelerates apoptosis in the nonsalvageable cells.
Fliss
H
H
Department of Physiology, Faculty of Medicine, University of Ottawa (Canada). hfliss@labsun1.med.uottawa.ca
Gattinger
D
D
D000818:Animals; D017209:Apoptosis; D003327:Coronary Disease / Q000473:pathology; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005821:Genetic Techniques; D007958:Leukocyte Count; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004247:DNA