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J Thorac Cardiovasc Surg. 2012 May;143(5):1167-75. doi: 10.1016/j.jtcvs.2011.06.045. Epub 2011 Nov 12.

The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components.

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Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Emory University, 550 Peachtree Street NE, Atlanta, GA 30308-2225, USA.



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.


Superoxide anion (O(2)(-)) generation: Isolated porcine PMNs were primed with cytochalasin B (5 μg/mL) and activated by N-formylmethionyl-leucyl-phenylalanine (100 nM). O(2)(-) release was quantified using lucigenin-enhanced chemiluminescence. Data were expressed as percent of stimulated control.


Both adenosine and lidocaine alone inhibited O(2)(-) 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 O(2)(-) generation in a synergistic manner. In addition, adenosine alone (0.1-10 μmol/L) inhibited O(2)(-) generation in primed but not activated PMNs, whereas lidocaine alone (1-100 μmol/L) inhibited O(2)(-) release in both primed and activated PMNs. Adenocaine further reduced O(2)(-) 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%).


Adenocaine suppresses multiple PMN functions including O(2)(-) 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.

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