Abstract 11735: The Hyperglycemic Exacerbation of Myocardial Infarct Size in Mice is Mediated by Splenocytes
Background: Acute hyperglycemia (HG) potentiates systemic inflammatory responses and exacerbates myocardial infarct (MI) size in both pre-clinical and clinical studies. As an important immune organ, accumulating evidence now shows that the spleen plays critical roles during myocardial infarction and subsequent healing. The current study was designed to determine whether splenocytes mediate the detrimental myocardial infarct exacerbation of ischemia/reperfusion injury caused by HG.
Methods and Results: C57BL6 (B6) mice underwent 30 min of LAD occlusion followed by 60 min of reperfusion. Acute HG was induced by injection of 20% Dextrose (2 g/kg, ip) 30 min before LAD occlusion. MI size (IF) and risk region (RR) were determined by TTC and Phthalo blue staining, respectively. HG significantly increased MI size by 41% in mice (p<0.01). Splenectomy (SPLX) performed 30 min before ischemia abolished the infarct exacerbating effect of HG. Acute adoptive transfer of splenocytes (SPAT) from B6 mice performed 25 min before ischemia effectively restored the effects of HG on MI in SPLX mice. ATL146e, an adenosine A2A receptor (A2AR) agonist, injected 5 min before reperfusion at 10μg/kg (iv) significantly reduced MI size in both HG (p<0.01) and SPLX+SPAT(B6)+HG groups (p<0.01). Interestingly, ATL146e failed to protect splenectomized HG mice after the adoptive transfer of splenocytes from A2AR knock-out mice (the SPLX+SPAT(A2AR KO)+HG group).
Conclusions: Splenocytes mediate the infarct exacerbating effect of acute HG. Adenosine2A receptors on splenocytes are responsible for mediating the vast majority of the cardioprotection afforded by A2AR agonists under HG conditions. These results may have implications for glycemic control during revascularization procedures and cardiac transplantation. Further studies are warranted to investigate the precise mechanisms of how HG activates splenocytes and which cell types are involved in this phenomenon.
Author Disclosures: Y. Tian: None. L. Chen: None. I.L. Kron: None. B.A. French: None. Z. Yang: None.
- © 2014 by American Heart Association, Inc.