Abstract 14337: Adenosine-lidocaine (Adenocaine™) Exerts Superior Anti-Neutrophil Effects by Synergistic Actions of its Components
Background: The combination of adenosine and lidocaine (adenocaine) exerts cardioprotection when used as a cardioplegia formulation. In addition, adenocaine decreases mortality and increases post-resuscitation hemodynamics after cardiac arrest. Both adenosine and lidocaine independently inhibit neutrophil (PMN) activity. However, the anti-inflammatory effects of adenocaine are unknown. We tested the hypothesis that adenocaine synergistically attenuates PMN activation and functions.
Methods and results: Isolated porcine PMNs were primed with 5µg/ml cytochalasin B (Cyto B), and activated by 100nM fMLP. Activated PMNs released O2− in a burst pattern [chemiluminescence, relative light units (RLU)/106 PMNs] to a peak of 207±54, which was inhibited by both adenosine (54±12) and lidocaine (58±19) alone in a dose-dependent manner. Adenocaine further inhibited O2− generation in a synergistic manner (18±2). Pro-inflammatory cytokines (PAF, IL-8, etc.) stimulate PMN adherence and transmigration during resuscitation. PAF (100nM)-induced CD11 b/c surface expression on PMNs (flow cytometry) was inhibited to 59.0±8.2% by 50µM adenosine (n=7, P <0.05), and 71.4±6.3% by 100µM lidocaine (n=7, P <0.05). Similarly, adenosine and lidocaine reduced the CD18 expression to 69.5±9.4% and 81.0±8.6% (n=7, P <0.05) vs Controls (100%), respectively. Adenocaine further decreased CD11b/c and CD18 expression to 48.2±10.3% (n=7, P <0.05) and 47.4±9.7% (n=7, P <0.05) of Controls (100%), respectively. Adenosine and lidocaine suppressed PMN adherence to cultured coronary endothelial cells by 29% and 27% respectively, while adenocaine further inhibited PMN adherence by 53% of control. PMN transendothelial migration induced by 10nM IL-8 (PMNs/well) was reduced by 20% of controls by 50µM adenosine whereas lidocaine (100µM) showed no significant effect; adenocaine did not further decrease PMN transmigration.
Conclusions: Adenocaine suppresses PMN functions by reducing O2− generation, adhesive molecule expression, and PMN adherence. The better physiological outcomes observed with adenocaine after resuscitation may be due to inhibition of PMN-mediated inflammation.
- © 2010 by American Heart Association, Inc.