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J Appl Physiol (March 8, 2007). doi:10.1152/japplphysiol.00033.2007
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Submitted on January 8, 2007
Accepted on March 2, 2007

Myocardial Infarct Size Measurement in the Mouse Chronic Infarction Model: Comparison of Area- and Length-Based Approaches

Junya Takagawa1, Yan Zhang1, Maelene L Wong1, Rich E Sievers1, Neel K Kapasi1, Yan Wang2, Yerem Yeghiazarians1, Randall J Lee1, William Grossman1, and Matthew L. Springer1*

1 Medicine, Cardiology Division, University of California, San Francisco, San Francisco, California, United States
2 FivePrime Therapeutics, inc., San Francisco, United States

* To whom correspondence should be addressed. E-mail: matt.springer{at}medicine.ucsf.edu.

Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, measurement of the infarcted area in tissue sections of the left ventricle (LV) is a standard approach to determine infarct size. This approach has also been used in the chronic infarct setting to measure infarct area several weeks post-MI. We tested the hypothesis that due to wall thinning that is known to occur in the chronic setting, the area measurement approach would be less appropriate. We compared infarct measurements in tissue sections based on (1) infarct area, (2) epicardial and endocardial infarct arc lengths, and (3) midline infarct arc length. Infarct size from all three measurement approaches correlated significantly with LV ejection fraction (LVEF) and wall motion abnormality. However, the infarct size values derived from area measurement were significantly smaller than those from the other measurements, and the range of values obtained was compressed 0.4-fold. The midline method was able to detect the expected size differences between infarcts of variable severity resulting from proximal vs. distal ligation of the coronary artery. Segmental infarct size was correlated with segmental wall motion abnormality. We conclude that both area- and length-based measurements can determine relative infarct size over a wide range of severity but the area-based measurements are substantially more compressed due to wall thinning, and that the estimation of infarct midlines is a simple, reliable approach to infarct size assessment.




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