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The novel non‐depolarizing, normokalemic cardioplegia formulation based on the combination of adenosine‐lidocaine (Adenocaine™) exerts superior anti‐neutrophil effects by synergistic actions of its components
Author(s) -
SHI WEIWEI,
JIANG RONG,
Dobson Geoffrey P,
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.lb548
Subject(s) - adenosine , lidocaine , cytochalasin b , superoxide , chemistry , pharmacology , cytochalasin , adenosine receptor , superoxide dismutase , medicine , in vitro , anesthesia , biochemistry , receptor , oxidative stress , agonist , cell , enzyme , cytoskeleton
Objectives We tested the hypothesis that the combination of adenosine and lidocaine (AL) synergistically attenuates neutrophil (PMN) functions. Methods 1. Superoxide anion (O2‐) generation, 2. PMN adherence, 3. Transmigration. Group differences (one‐way ANOVA) were accepted at P value<0.05. Results The isolated porcine PMNs released superoxide dismutase (0.1mg/ml)‐sensitive O2‐ in a burst pattern upon activation. Both adenosine and lidocaine alone inhibited O2‐ production in a dose‐dependent pattern. AL further inhibited O2‐ generation in a synergistic manner. In addition, adenosine (0.1–10 μM) inhibited O2‐ generation by cytochalasin B (priming), whereas lidocaine (1–100 μM) inhibited O2‐ release stimulated by both cytochalasin B and fMLP (activation). Both adenosine and lidocaine alone inhibited PAF‐induced PMN adherence to endothelial cells. Adenosine (50μM) and lidocaine (100 μM) decreased adherence to 71.6±5.4% (n=8, P<0.05) and 73.2±8.1% (n=7, P<0.05) of stimulated control, respectively. AL further suppressed adherence to 47.2±4.3% (n=7, P<0.05). Adenosine (100μM) reduced PMN transendothelial migration to 80.1±6.7% of control (n=6, P<0.05), whereas lidocaine (100μM) showed no significant inhibition. AL did not further decrease transmigration. Conclusions AL suppresses PMN O2‐ generation and adherence in a synergistic manner relative to adenosine or lidocaine alone.