A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion.
BACKGROUND
Repetitive brief myocardial ischemia has been implicated in the pathogenesis of the ventricular dysfunction associated with ischemic cardiomyopathy and myocardial hibernation. In this study we examine the effects of repetitive ischemia and reperfusion (I/R) on murine myocardium.


METHODS
C57/BL6 mice underwent daily 15 min left anterior descending coronary occlusions followed by reperfusion. After 3, 5, 7, 14, 21 and 28 days, echocardiographic studies were performed, and hearts of I/R and sham-operated animals were processed for histological examination.


RESULTS
Histological studies showed no evidence of myocardial necrosis in the ischemic region. Quantitative assessment of collagen revealed a marked persistent interstitial deposition of collagen after seven days I/R in the anterior left ventricular wall (sham 4.6 +/- 2.0 %, I/R 21.5 +/- 6.5 %, p < 0.05). Echocardiographic studies showed persistent regional anterior wall dysfunction in I/R animals. Histological evaluation showed absence of neovessel formation. After discontinuation of the I/R protocol, fibrosis and regional ventricular dysfunction decreased within 60 days.


CONCLUSIONS
Repetitive brief murine myocardial I/R induces reversible fibrotic remodeling and ventricular dysfunction, without myocardial infarction and necrosis, and may play a role in the pathogenesis of ischemic cardiomyopathy and myocardial hibernation.
Dewald
O
O
Section of Cardiovascular Sciences and DeBakey Heart Center, Baylor College of Medicine, and The Methodist Hospital, Houston, TX, USA. Oliver.Dewald@ukb.uni-bonn.de.
Frangogiannis
N G
NG
Zoerlein
M P
MP
Duerr
G D
GD
Taffet
G
G
Michael
L H
LH
Welz
A
A
Entman
M L
ML
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D015427:Reperfusion Injury / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000473:pathology