Myocardial ischemia and reperfusion - a murine model .
Michael, Lloyd H., Mark L. Entman, Craig J. Hartley, Keith A. Youker,
Jessica Zhu, Stuart R. Hall, Hal K. Hawkins, Kurt Berens, and
Christie M. Ballantyne.
Sections of Cardiovascular Sciences, Leukocyte Biology and
Atherosclerosis and Lipoprotein Research, Department of Medicine and
Pediatrics, The Methodist Hospital and The DeBakey Heart Center,
Baylor College of Medicine, Houston, Texas, Department of Pathology,
The University of Texas Medical Branch, Galveston, Texas
APStracts 2:0268H, 1995.
Myocardial ischemia followed by reperfusion promotes a complex series
of inflammatory reactions as noted in a variety of studies using
large animals. With development of genetically altered mice, there is
intense interest in developing murine models to study mechanisms
operative in cardiovascular disease. This study reports development
of a mouse model to study the effects of coronary artery occlusion
and reperfusion and details the method required to perform these
studies both acutely and chronically. Using the mouse we applied a
left anterior descending coronary artery occlusion either permanently
or for 30 or 60 minutes followed by reperfusion allowing flow through
the previously occluded coronary artery bed. Reperfusion was
documented visually as well as by using Doppler ultrasound, and
histopathologic techniques. The area at risk and infarct size were
assessed by Evans blue dye and TTC staining with computerized
planimetry using an image analysis software program. The infarct as %
of the area at risk and infarct size as % of the left ventricle in 13
mice with permanent occlusion was 68.6% +/- 4.4% and 28.0% +/- 2.8%,
respectively. Reperfusion after occlusions of 60 and 30 minutes
resulted in a significant decrease in infarct size as a % of the area
at risk compared to permanent occlusion. Histologic examination of
the ischemic and reperfused myocardium shows infiltration of
leukocytes into the ischemic region as well as contraction bands
classically associated with reperfusion. This new model allows
assessment of area at risk, infarct size, cardiac function and
pathophysiology in the mouse. With the current technology to develop
genetically altered mice for over-expression or targeted mutations of
various genes, this model allows a unique approach to understand the
complex pathophysiology of ischemia and reperfusion injury.
Received 25 July 1994; accepted in final form 14 June 1995.
APS Manuscript Number H650-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.