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Updated: Aug 29, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Modified two-step model for studying the inflammatory response during myocardial ischemia and reperfusion in mice
Willeke M C Jong1, Pieter H Reitsma, Hugo ten Cate
1Department of Cardiology, Cardiovascular Research Institute Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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.
Insights
This study introduces a less invasive mouse model for myocardial ischemia-reperfusion (MI-R) using lateral thoracotomy. The new model offers stable hemodynamics and allows for studying inflammation without surgical interference.
Area of Science:
- Cardiovascular Research
- Surgical Innovation
- Inflammation and Immunity
Background:
- Myocardial ischemia-reperfusion (MI-R) studies require models that isolate surgical effects from injury.
- Existing closed-thorax models with median thoracotomy can introduce confounding surgical inflammatory factors.
- A less invasive approach is needed to accurately study MI-R and associated inflammatory responses.
Purpose of the Study:
- To develop a minimally invasive mouse model for studying myocardial ischemia-reperfusion (MI-R).
- To enable the investigation of coagulation, inflammation, and reperfusion injury interactions.
- To establish a model with stable hemodynamics and minimal procedure-related confounding factors.
Main Methods:
- Reversible ligation of the left interventricular branch artery (LIB) in mice.
- Replacement of median thoracotomy with lateral thoracotomy for LIB access.
- Monitoring of body weight, cytokine levels, mean arterial pressure (MAP), and electrocardiography (ECG).
- Assessment of infarct size using Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining.
Main Results:
- Lateral thoracotomy allowed for rapid body weight regain and return of cytokine levels to baseline.
- Stable mean arterial pressure (MAP) during ischemia (78 mmHg) and reperfusion (67 mmHg) was observed.
- Transient ST elevation on ECG confirmed reversible transmural ischemia and reperfusion.
- Procedure-related mortality was 13%, comparable to existing methods.
Conclusions:
- The novel lateral thoracotomy model provides stable, near-physiologic hemodynamics for MI-R studies.
- This minimally invasive approach effectively separates surgical effects from MI-R-induced inflammation.
- The model facilitates the study of inflammatory responses in myocardial ischemia-reperfusion with reduced surgical artifact.
