Abstract 19578: Title: Natural Killer T cells Play a More Critical Role in Reperfusion Injury Than in the Hyperglycemic Exacerbation of Infarct Size
Introduction: Invariant Natural Killer T (iNKT) cells express a T cell receptor encoded by the Jalpha18 gene that recognizes glycolipid antigens presented by CD1d. These same iNKT cells have recently been implicated in the hyperglycemic exacerbation of lung ischemia/reperfusion injury. Thus, we hypothesized that Jalpha18-/- mice, which lack iNKT cells, would similarly be protected against the hyperglycemic exacerbation of cardiac injury in the mouse model of reperfused myocardial infarction (MI).
Methods: Reperfused MI was performed in euglycemic (n=8) and hyperglycemic (n=7) C57Bl/6 wild-type (WT) mice, as well as in congenic euglycemic (n=11) and hyperglycemic (n=8) Jalpha18-/- mice. MI consisted of 30 min coronary occlusions followed by 2 h reperfusion. Infarct size was determined by digital planimetry after TTC and Phthalo blue staining, and was reported as infarct size as percent area-at-risk (%A@R).
Results: Infarct size was reduced by 56% in euglycemic Jalpha18-/- mice compared to euglycemic WT mice (18±3% vs. 41±5%, mean±SEM, p<0.05). Infarct size was also reduced in hyperglycemic Jalpha18-/- mice compared to hyperglycemic WT mice, albeit to a much lesser extent (52±3% vs. 63±3%, p<0.05). Further, the areas at risk as percent of the left ventricular (LV) mass were similar for all groups (p=NS).
Conclusions: With regard to mechanism, these results clearly demonstrate that iNKT cells and innate immune responses contribute importantly to reperfusion injury. From a translational perspective, the results predict that interventions focused on suppressing the innate immune response during reperfusion will be significantly more effective in euglycemic patients than in those suffering from stress hyperglycemia.
- © 2012 by American Heart Association, Inc.