title: Adenosine, lidocaine and Mg2+ improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model.
abstract: BACKGROUND
  The combination of Adenosine (A), lidocaine (L) and Mg(2+) (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model.
  
  
  METHODS
  Pigs (37 to 42 kg) were randomized into: 1) Control (n = 8) or 2) ALM (n = 8) followed by lipopolysaccharide infusion (1 μg ∙ kg(-1) ∙ h(-1)) for five hours. ALM treatment consisted of 1) a high dose bolus (A (0.82 mg/kg), L (1.76 mg/kg), M (0.92 mg/kg)), 2) one hour continuous infusion (A (300 μg ∙ kg(-1) ∙ min(-1)), L (600 μg ∙ kg(-1) ∙ min(-1)), M (336 μg ∙ kg(-1) ∙ min(-1))) and three hours at a lower dose (A (240 ∙ kg(-1) ∙ min(-1)), L (480 μg ∙ kg(-1) ∙ min(-1)), M (268 μg ∙ kg(-1) ∙ min(-1))); controls received normal saline. Hemodynamic, cardiac, pulmonary, metabolic and renal functions were evaluated.
  
  
  RESULTS
  ALM lowered mean arterial pressure (Mean value during infusion period: ALM: 47 (95% confidence interval (CI): 44 to 50) mmHg versus control: 79 (95% CI: 75 to 85) mmHg, P < 0.0001). After cessation of ALM, mean arterial pressure immediately increased (end of study: ALM: 88 (95% CI: 81 to 96) mmHg versus control: 86 (95% CI: 79 to 94) mmHg, P = 0.72). Whole body oxygen consumption was significantly reduced during ALM infusion (ALM: 205 (95% CI: 192 to 217) ml oxygen/min versus control: 231 (95% CI: 219 to 243) ml oxygen/min, P = 0.016). ALM treatment reduced pulmonary injury evaluated by PaO2/FiO2 ratio (ALM: 388 (95% CI: 349 to 427) versus control: 260 (95% CI: 221 to 299), P = 0.0005). ALM infusion led to an increase in heart rate while preserving preload recruitable stroke work. Creatinine clearance was significantly lower during ALM infusion but reversed after cessation of infusion. ALM reduced tumor necrosis factor-α peak levels (ALM 7121 (95% CI: 5069 to 10004) pg/ml versus control 11596 (95% CI: 9083 to 14805) pg/ml, P = 0.02).
  
  
  CONCLUSIONS
  ALM infusion induces a reversible hypotensive and hypometabolic state, attenuates tumor necrosis factor-α levels and improves cardiac and pulmonary function, and led to a transient drop in renal function that was reversed after the treatment was stopped.
authors.affiliation: Department of Anesthesiology, Aarhus University Hospital, Nørrebrogade 44 building 21 1st floor 8000, Aarhus, Denmark. granfeldt@gmail.com.|Department of Anesthesiology, Regional Hospital of Randers, Skovlyvej 1, 8930, Randers, Denmark. granfeldt@gmail.com.
authors.forename: Asger
authors.initials: A
authors.lastname: Granfeldt
authors.affiliation: Heart, Trauma & Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, School of Medicine and Dentistry, James Cook University, Pharmacy and Medical Research Building 47, Rm 113B, Townsville, Queensland, Australia. hayley.letson@jcu.edu.au.
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Letson
authors.affiliation: Heart, Trauma & Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, School of Medicine and Dentistry, James Cook University, Pharmacy and Medical Research Building 47, Rm 113B, Townsville, Queensland, Australia. geoffrey.dobson@jcu.edu.au.
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Dobson
authors.affiliation: The Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Emory University School of Medicine, 387 Technology Circle Suite 180, Atlanta, Georgia 30313, USA. weiweishimd@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: The Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Emory University School of Medicine, 387 Technology Circle Suite 180, Atlanta, Georgia 30313, USA. jvinten@emory.edu.
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
authors.affiliation: Department of Anesthesiology, Aarhus University Hospital, Nørrebrogade 44 building 21 1st floor 8000, Aarhus, Denmark. else.toennesen@aarhus.rm.dk.
authors.forename: Else
authors.initials: E
authors.lastname: Tønnesen
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008012:Lidocaine / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000008:administration & dosage*; D011897:Random Allocation; D012129:Respiratory Function Tests / Q000379:methods; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008012:Lidocaine; D008274:Magnesium; D000241:Adenosine