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A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery
Published on: April 10, 2014
A Novel Mouse Model of Liver Ischemic/Reperfusion Injury and its Differences to the Existing Model
Jianjian Zhang1, Ming Zhang1, Jianjun Zhang1
1a Department of Transplantation and Hepatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China.
Background:
Ischemia of the cephalad lobes (70% of liver mass) is a frequently employed mouse hepatic ischemia/reperfusion (I/R) model that does not involve outflow occlusion. This model produces results with relatively large variances.
Materials And Methods:
A novel model of ischemia of the left lateral lobe (35% of liver mass) that involves temporarily occluding the blood supply to the cephalad lobes to expel blood followed by occlusion of both the inflow and outflow of the left lateral lobe, was developed. Mice in the 35% (novel) and 70% (existing) model groups were subjected to I/R injury, and biochemical and histological analyses of blood and liver samples were performed. Tissue oxygen partial pressure (tPO2) measurements in the ischemic lobes were also performed to determine whether the hepatic tissue was in a stable hypoxic state. Statistical analyses of the biochemical results, histological scores, and tPO2 levels were performed from which coefficients of variation (CV) were calculated.
Results:
The CVs of the aminotransferase activities, histological scores, and tPO2 levels were much lower in the 35% group than those in the 70% group. The tPO2 measurements demonstrated that inflow occlusion in the 70% model did not result in a stable hypoxic state, even after the portal triads were ligated and severed, indicating that there was blood reflux from the vena cava, which would be responsible for the variations in results with the 70% I/R model.
Conclusions:
The new 35% I/R model leads to reproducible results because both inflow and outflow of the ischemic lobe are occluded.
Insights
A new 35% liver ischemia/reperfusion (I/R) model offers improved reproducibility over the existing 70% model. This novel approach ensures stable hypoxia for more reliable experimental outcomes in hepatic I/R studies.
Area of Science:
- Hepatology
- Surgical Innovation
- Experimental Models
Background:
- The established 70% mouse hepatic ischemia/reperfusion (I/R) model, involving cephalad lobe ischemia without outflow occlusion, exhibits significant result variability.
- This variability is attributed to incomplete blood expulsion and potential vena cava reflux, hindering stable hypoxic conditions.
Purpose of the Study:
- To develop and validate a novel, more reproducible mouse model for hepatic ischemia/reperfusion (I/R) injury.
- To compare the reproducibility and stability of a new 35% liver mass I/R model against the existing 70% model.
Main Methods:
- A novel 35% liver mass I/R model was created by occluding inflow and outflow to the left lateral lobe.
- The existing 70% model (cephalad lobe ischemia) was used for comparison.
- Biochemical, histological, and tissue oxygen partial pressure (tPO2) analyses were conducted on both models.
Main Results:
- The 35% I/R model demonstrated significantly lower coefficients of variation (CV) in aminotransferase activities, histological scores, and tPO2 levels compared to the 70% model.
- tPO2 measurements confirmed that the 70% model failed to achieve stable hypoxia due to blood reflux, unlike the 35% model.
Conclusions:
- The novel 35% hepatic I/R model provides more reproducible results due to complete occlusion of both inflow and outflow.
- This enhanced model facilitates stable hypoxic conditions, reducing experimental variance in hepatic I/R research.

