title: The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest.
abstract: OBJECTIVE
  Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction.
  
  
  METHODS
  Pigs were randomized to: (1) sham (n=7), (2) cardiac arrest (CA; n=16), or 3) cardiac arrest+adenocaine (CA+AL; n=12). After 7 min of electrically induced ventricular fibrillation, start of CPR was followed by infusion of saline (CA) or adenocaine (CA+AL) for 6 min. Haemodynamics, cardiodynamics (pressure-volume loops) and leucocyte superoxide anion generation were assessed. Neurological function was evaluated after 24h by histology and neurological deficit score (0=normal; 500=brain dead).
  
  
  RESULTS
  Rate of ROSC was comparable between groups: CA group 11/16 and CA+AL group 7/12 p=0.57). Cardiac index transiently increased after ROSC in both groups. Left ventricular dysfunction demonstrated by a rightward shift of the intercept of end-systolic pressure-volume relations in CA was avoided in the CA+AL group. Leucocyte superoxide anion generation 2h after ROSC was significantly attenuated in the CA+AL group compared to the CA group. Neurological deficit scores [CA: median: 17.5(IQR:0-75) and CA+AL: 35(IQR:15-150)] and histopathological damage were comparable in both groups (p=0.37).
  
  
  CONCLUSIONS
  Infusion of adenocaine during early resuscitation from CA significantly improved early post-resuscitation cardiac function and attenuated leucocyte superoxide anion generation, without a change in post-ROSC neurological function. (IACUC protocol number 023-2009).
authors.affiliation: Department of Anesthesiology, Aarhus University Hospital NBG, Aarhus, Denmark; Department of Internal Medicine, Regional Hospital of Randers, Randers, Denmark. Electronic address: granfeldt@gmail.com.
authors.forename: Asger
authors.initials: A
authors.lastname: Granfeldt
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shi
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schmarkey
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: C Collin
authors.initials: CC
authors.lastname: Bone
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
authors.forename: Lise
authors.initials: L
authors.lastname: Wogensen
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Dobson
authors.forename: Else
authors.initials: E
authors.lastname: Tønnesen
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001926:Brain Death; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D017023:Coronary Angiography; D004195:Disease Models, Animal; D004338:Drug Combinations; D006323:Heart Arrest / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics; D008012:Lidocaine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control*; D015996:Survival Rate; D013552:Swine
chemical_list: D002317:Cardiovascular Agents; D004338:Drug Combinations; C572495:adenocaine; D008012:Lidocaine; D000241:Adenosine; D010100:Oxygen
keywords: Adenosine; Cardiac arrest; Lidocaine; Myocardial dysfunction; Pig; Resuscitation