Abstract 5867: Reduced Myocardial Infarct Size in Interferon-Gamma Knock-out Mice Implicates CD4+ T Cells in Reperfusion Injury
Introduction: Recent studies show that CD4+ T lymphocytes upregulate innate immune responses largely through the release of IFN-γ, suggesting the hypothesis that IFN-γ may contribute to the pro-inflammatory component of reperfusion injury during myocardial infarction (MI).
Methods: Wild-type (WT) mice (C57BL/6J) and congenic IFN-γ knock out (KO) mice underwent 45 min of LAD occlusion and 24 hours of reperfusion. Mice from both strains were treated either with vehicle or a selective adenosine 2A receptor (A2AR) agonist (ATL146e) at a dose of 10 μg/kg IP injected 2 min before initiating reperfusion. Twenty-four hours later, infarct size and risk region were evaluated by TTC and Phthalo blue staining, respectively.
Results: Risk region (RR) as % of LV mass ranged from 33–50% and was not statistically different between the four groups. Mean infarct size in vehicle-treated WT mice (n = 9) was 61±2% of RR. Consistent with previous studies, transient A2AR activation reduced infarct size by 30% (n = 8, p<0.05 vs. vehicle-treated WT). In IFN-γ KO mice (n=9), infarct size was significantly smaller than that found in WT mice (p<0.05) and was comparable to that found in WT mice treated with the A2AR agonist (47±3 vs. 43±4%, p<NS). A2AR activation caused no further reduction of infarct size in IFN-γ KO mice (n=5, p=NS vs. IFN-γ KO).
Conclusions: The results indicate that IFN-γ plays an important role in mediating myocardial reperfusion injury. The fact that A2A receptor activation fails to provide any additional cardioprotection in IFN-γ KO mice suggests a mechanism whereby the infarct size reduction attributable to selective A2AR activation involves IFN-γ signaling, probably through CD4+ T cells.