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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/H1825    most recent 495.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Rork, T. H. Articles by Linden, J. PubMed PubMed Citation Articles by Rork, T. H. Articles by Linden, J.

Adenosine A_2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation

¹Robert M. Berne Cardiovascular Research Center and ²Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia

Submitted 12 May 2008 ; accepted in final form 22 August 2008

Mast cells are found in the heart and contribute to reperfusion injury following myocardial ischemia. Since the activation of A_2A adenosine receptors (A_2AARs) inhibits reperfusion injury, we hypothesized that ATL146e (a selective A_2AAR agonist) might protect hearts in part by reducing cardiac mast cell degranulation. Hearts were isolated from five groups of congenic mice: A_2AAR^+/+ mice, A_2AAR^–/– mice, mast cell-deficient (Kit^W-sh/W-sh) mice, and chimeric mice prepared by transplanting bone marrow from A_2AAR^–/– or A_2AAR^+/+ mice to radiation-ablated A_2AAR^+/+ mice. Six weeks after bone marrow transplantation, cardiac mast cells were repopulated with >90% donor cells. In isolated, perfused hearts subjected to ischemia-reperfusion injury, ATL146e or CGS-21680 (100 nmol/l) decreased infarct size (IS; percent area at risk) from 38 ± 2% to 24 ± 2% and 22 ± 2% in ATL146e- and CGS-21680-treated hearts, respectively (P < 0.05) and significantly reduced mast cell degranulation, measured as tryptase release into reperfusion buffer. These changes were absent in A_2AAR^–/– hearts and in hearts from chimeric mice with A_2AAR^–/– bone marrow. Vehicle-treated Kit^W-sh/W-sh mice had lower IS (11 ± 3%) than WT mice, and ATL146e had no significant protective effect (16 ± 3%). These data suggest that in ex vivo, buffer-perfused hearts, mast cell degranulation contributes to ischemia-reperfusion injury. In addition, our data suggest that A_2AAR activation is cardioprotective in the isolated heart, at least in part by attenuating resident mast cell degranulation.

Langendorff; tryptase; ATL146e; CGS-21680; bone marrow chimera