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Physiology in Press

First published online on May 6, 2004.
Experimental Physiology (2004)
DOI: 10.1113/expphysiol.2004.027276
© The Physiological Society 2004

A more recent version of this article appeared on July 1, 2004
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Received January 16, 2004
Revised March 1, 2004
Accepted after revision May 6, 2004


Heart/cardiac muscle

Critical appraisal of the mouse model of myocardial infarction

Naomi M Degabriele 1, Uta Griesenbach 1*, Kaori Sato 2, Mark J Post 3, Jie Zhu 1, John Williams 1, Peter K Jeffery 1, Duncan M Geddes 1, Eric W. F. W Alton 1

1 Imperial College London Faculty of Medicine,
2 Boston University School of Medicine
3 Maastricht University

* To whom correspondence should be addressed. E-mail: u.griesenbach{at}imperial.ac.uk.


   Abstract
In order to critically evaluate the utility of a mouse model of myocardial infarction (MI) for therapeutic studies, we investigated survival, hemodynamic measurements and histopathology in mice with an occluding suture placed at one of three distinct sites along the left anterior descending coronary artery. The suture was placed at the atrio-ventricular juncture (High), or at two sites more distally towards the base (Middle and Low). In the High group, only 33% of animals survived seven days after MI (p<0.05 compared to all other groups). Only the Middle group had significantly reduced hemodynamics compared to sham animals (maximum left ventricular pressure: 55.9 +/- 3.5 vs 80.8 +/-5.1 mm Hg, maximum dP/dT: 2003 +/- 172 vs 4402 +/-491, p<0.01). Histological examination showed morphological changes in all MI groups. The Middle group had larger lesions than the Low group (p<0.05). Lesions in the anterior and lateral walls correlated, albeit weakly, with cardiac function. Power calculations indicated that, despite a certain amount of intra-group variation, the Middle Suture model may be useful for therapeutic studies assessing the effects of treatment on cardiac function and overall lesion size.

Key Words: Angiogenesis, Heart, Myocardium







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