The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components
Shi, Weiwei, Jiang, Rong, Dobson, Geoffrey P., Granfeldt, Asger, and Vinten-Johansen, Jakob (2012) The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components. Journal of Thoracic and Cardiovascular Surgery, 143 (5). pp. 1167-1175.
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Objective: A new strategy of normothermic cardioplegia based on the combination of adenosine and lidocaine (adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) achieves nondepolarized arrest at normokalemia. Both adenosine and lidocaine independently inhibit neutrophil (polymorphonuclear neutrophil; PMN) activity. However, whether adenocaine exerts greater anti-inflammatory effects is not known. We tested the hypothesis that adenocaine synergistically attenuates PMN functions.
Methods: Superoxide anion (O2−) generation: Isolated porcine PMNs were primed with cytochalasin B (5 μg/mL) and activated by N-formylmethionyl-leucyl-phenylalanine (100 nM). O2− release was quantified using lucigenin-enhanced chemiluminescence. Data were expressed as percent of stimulated control.
Results: Both adenosine and lidocaine alone inhibited O2− production in a dose-dependent manner (adenosine reduced to 67% ± 8.4% and 21% ± 2.2% of maximal stimulation at 0.1 and 10 μmol/L, respectively, lidocaine reduced to 57.9% ± 18.6% and 28% ± 5% at 10 and 100 μmol/L, respectively). Adenocaine further reduced O2− generation in a synergistic manner. In addition, adenosine alone (0.1–10 μmol/L) inhibited O2− generation in primed but not activated PMNs, whereas lidocaine alone (1–100 μmol/L) inhibited O2− release in both primed and activated PMNs. Adenocaine further reduced O2− generation because of inhibition of both priming and activation stages. Both adenosine and lidocaine alone and adenocaine comparably inhibited platelet activating factor–induced CD11 b/c surface expression on PMNs (flow cytometry), but adenocaine further suppressed both CD18 expression (to 47.4% ± 9.7%) and PMN adherence (to 47.2% ± 4.3%) compared with adenosine and lidocaine alone. Transmigration of calcein-acetyoxymethyl–labeled PMNs through transwells seeded with cultured coronary artery endothelial cells was reduced comparably by adenosine (to 80.1% ± 6.7%) and adenocaine (67.3% ± 9.6%).
Conclusions: Adenocaine suppresses multiple PMN functions including O2− generation, adhesion molecule expression, PMN adherence, and transmigration. In addition to inducing nondepolarized arrest, adenocaine cardioplegia may exert cardioprotection by inhibiting PMN-mediated inflammatory responses.
|Item Type:||Article (Refereed Research - C1)|
|Date Deposited:||08 Jul 2012 23:45|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%|
|Citation Count from Web of Science||