Premium
Resident cardiac mast cells contribute to ischemia‐reperfusion injury in the isolated, perfused mouse heart
Author(s) -
Rork Tyler Habkirk,
Wallace Kori L,
Kennedy Dylan P,
Marshall Melissa A,
Lankford Amy R,
Linden Joel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.47
Subject(s) - degranulation , medicine , agonist , tryptase , ischemia , reperfusion injury , adenosine , adenosine receptor , pharmacology , cardiology , endocrinology , anesthesia , receptor , mast cell , immunology
Studies show that resident cardiac mast cells (MCs) play an injurious role in various cardiac pathologies. We hypothesize that MC degranulation contributes to ischemia‐reperfusion (I/R) injury, and that an adenosine A 2A receptor (A 2A AR) agonist would limit infarct size (IS) by inhibiting MC degranulation. Isolated mouse hearts were subjected to 30 minutes ischemia and 30 minutes reperfusion. Either vehicle or 100 nM ATL146e (a specific A 2A AR agonist; gift from Jayson Rieger, Adenosine Therapeutics, LLC) was infused throughout reperfusion. Coronary effluent was assayed for tryptase activity and hearts were TTC stained to determine IS. Vehicle‐treated hearts had an average IS of 38±2 % area at risk whereas ATL146e treatment decreased IS to 24±2% (P<0.05). Also, tryptase release was significantly less in ATL146e‐ versus vehicle‐treated hearts at several time points during reperfusion. Studies were repeated in A 2A AR KO mice and ATL146e had no effect on IS or tryptase release. Mice with genetic MC deficiency were protected in the vehicle‐treated state (16±3% IS), and ATL146e treatment provided no additional benefit (11±3% IS). These findings support the hypothesis that degranulation of MCs contributes to I/R‐mediated cardiac damage and cardiac MC degranulation can be inhibited by A 2A AR activation and attenuate I/R injury. Support provided by NIH grant R01‐HL37942. THR is an AHA postdoctoral fellow (0725488U).