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PAR1 inhibition does not enhance the cardioprotective effect of postconditioning
Author(s) -
Jiang Rong,
Rutledge Caleb,
Shi Weiwei,
Guyton Robert A,
VintenJohansen Jakob
Publication year - 2010
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.24.1_supplement.601.8
Subject(s) - cardioprotection , medicine , antagonist , pharmacology , in vivo , ischemia , myocardial infarction , saline , reperfusion injury , anesthesia , cardiology , receptor , biology , microbiology and biotechnology
Postconditioning (postcon) protects the heart from ischemia reperfusion (IR) injury. Protease activated receptor1 (PAR1) inhibition has protective effects after IR. Therefore, we hypothesize that if postcon and pharmacological PAR1 inhibition target the same pathway, and the combination of postcon and PAR1 inhibition may not have additive protective effect. Methods In anesthetized open‐chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 hours. Rats were randomly assigned to1) Control: saline; 2) PAR1 antagonist (BMS 226001) 1mg/Kg was administered 5 min before R; 3) Postcon with 3 cycles of 10 s R and 10 s re‐occlusion and 4) BMS 1 mg/Kg plus postcon. Results Area at risk (36%–39%) was comparable among 4 groups. Compared to control, infarct size (TTC staining) was significantly less in BMS, postcon and the combination groups. The combination of BMS and postcon did not further significantly reduce infarct size compared to either intervention alone. Conclusions Inhibition of PAR1 and postcon alone at reperfusion are cardioprotective in vivo; however, concomitant PAR1 inhibition does not enhance the cardioprotection of postcon.Group N AAR/LV (%) An/AAR (%)Control 7 37.9 ± 2.4 57.0 ± 2.1 BMS 8 38.1 ± 2.5 42.5 ± 2.5 * Postcon 7 39.3 ± 2.1 39.1 ± 2.3 * BMS + Postcon 7 35.6 ± 1.4 39.9 ± 3.0 *Values are expressed as mean ± S.E.M. * P < 0.05 vs. values in control.