Modified Two-Step Model for Studying the Inflammatory Response during Myocardial Ischemia and Reperfusion in Mice
Abstract:Studies of myocardial ischemia-reperfusion (MI-R) in the mouse can be accomplished by use of reversible ligation of the left interventricular branch artery (LIB). To study interactions of coagulation, inflammation, and reperfusion injury, the model should not be influenced by effects of the surgery. In existing closed-thorax mouse models, the release of inflammatory factors attributable to surgical intervention could be separated from the release resulting from induction of MI-R. In these models, the final myocardial injury was induced by reversible closure of the LIB several days after preparative surgery that included median thoracotomy.
In an attempt to develop a less invasive procedure to approach the LIB, we replaced median thoracotomy with lateral thoracotomy. After this procedure, body weight was regained within four days, and on days 9 to 11 after the preparative surgery, cytokine values were back to baseline. During one hour of ischemia, mean arterial pressure (MAP) remained at 78 ± 2 mmHg. After induction of reperfusion, MAP was 67 ± 4 mmHg, indicating better perfusion pressure of myocardial tissue at the microcirculatory level than that in simple open-thorax models.
Electrocardiographic recording revealed transient ST elevation indicating reversible transmural ischemia and reperfusion. Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining visualized the extent of area of infarction (AOI) and area at risk (AAR). The procedure-related mortality was 13%, which compared well with published data from median thoracotomy studies.
We conclude that our new model provides stable near-physiologic hemodynamics and allows study of the inflammatory response resulting from MI-R, with low procedure-related mortality.
Document Type: Research Article
Affiliations: 1: Laboratory for Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 2: Department of Internal Medicine and Department of Biochemistry, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, Maastricht, The Netherlands 3: Department of Cardiology, Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Publication date: October 1, 2003
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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