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Updated: Mar 19, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Exogenous Administration of Recombinant MIF at Physiological Concentrations Failed to Attenuate Infarct Size in a
Xavier Rossello1, Niall Burke1, Christian Stoppe2
1The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX 2, UK.
Purpose:
Evidence suggests a two-pronged role of endogenous macrophage migration inhibitory factor (MIF) release in ischemia/reperfusion injury. We aimed to assess whether its exogenous administration confers cardioprotection.
Methods:
Male C57/BL6 mice were randomly allocated to receive recombinant mouse MIF (rMIF) at physiological (ng/mL) concentrations in a dose-response fashion before or after a protocol of 35 min of ischemia and 2 h of reperfusion in an isolated Langendorff-perfused model with infarct size as endpoint. Isolated primary cardiomyocytes were also used for cell survival studies using rMIF at a supra-physiological concentration of 1 μg/mL. Pro-survival kinase activation was also studied using Western blot analyses.
Results:
Exogenous MIF did not elicit a cardioprotective effect either when administered before the ischemic insult or when applied at reperfusion. rMIF did not confer protection when it was applied immediately before or after a hypoxia/reoxygenation insult in primary isolated cardiomyocytes. Consistently, hearts treated with MIF did not show a significant increase in phosphorylated Akt and ERK1/2.
Conclusion:
The exogenous administration of rMIF in a physiological concentration range both before ischemia and at reperfusion did not show cardioprotective effects. Although these results do not address the role of endogenous MIF after an ischemic insult followed by reperfusion, they may limit the potential translational value of rMIF.
Insights
Exogenous macrophage migration inhibitory factor (MIF) did not protect the heart from ischemia/reperfusion injury in mice or isolated cells. These findings suggest limited translational value for exogenous MIF in treating heart attacks.
Area of Science:
- Cardiovascular Research
- Cellular and Molecular Medicine
- Immunology
Background:
- Endogenous macrophage migration inhibitory factor (MIF) plays a complex role in ischemia/reperfusion (I/R) injury.
- Investigating exogenous MIF's potential cardioprotective effects is crucial for therapeutic development.
Purpose of the Study:
- To determine if exogenous administration of recombinant mouse MIF (rMIF) confers cardioprotection against I/R injury.
- To evaluate the impact of rMIF on cell survival and pro-survival kinase activation in cardiac cells.
Main Methods:
- Male C57/BL6 mice underwent a 35-min ischemia and 2-h reperfusion protocol using an isolated Langendorff-perfused model.
- Recombinant mouse MIF (rMIF) was administered at physiological concentrations before or after ischemia; infarct size was the endpoint.
- Primary cardiomyocytes were subjected to hypoxia/reoxygenation with rMIF treatment, and pro-survival kinase activation (Akt, ERK1/2) was assessed via Western blot.
Main Results:
- Exogenous rMIF did not provide cardioprotection when administered before ischemia or at reperfusion in the Langendorff model.
- rMIF failed to protect isolated cardiomyocytes against hypoxia/reoxygenation injury.
- No significant increase in phosphorylated Akt or ERK1/2 was observed in MIF-treated hearts.
Conclusions:
- Exogenous rMIF administration at physiological concentrations does not confer cardioprotection against ischemia/reperfusion injury.
- These findings may limit the translational potential of using exogenous MIF for treating cardiac I/R injury.
- Further research is needed to fully elucidate the role of endogenous MIF in cardiac I/R injury.
