Adenosine, lidocaine and Mg2+ improves cardiac and pulmonary function, induces reversible hypotension and exerts anti-inflammatory effects in an endotoxemic porcine model

• Type of Material: Article
• Authors: Asger Granfeldt, Aarhus University Hospital; Hayley L. Letson, James Cook University; Geoffrey P. Dobson, James Cook University; Weiwei Shi, Emory University; Jakob Vinten-Johansen, Emory University; Else Tonnesen, Aarhus University Hospital
• Language: English
• Date: 2014-01-01
• Publisher: Biomed Central Ltd
• Publication Version: Final Published Version
• Copyright Statement: © Granfeldt et al.; licensee BioMed Central. 2014
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13054-014-0682-y
• Title of Journal or Parent Work: Critical Care
• Volume: 18
• Issue: 6
• Start Page: 682
• End Page: 682
• Grant/Funding Information: This study was supported by The Augustinus Foundation, Copenhagen, Denmark and the Health Research Fund of Central Denmark Region, Viborg, Denmark.
• Keywords: SEVERE SEPSIS; SEPTIC SHOCK; ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; Critical Care Medicine; MILD HYPERLACTATEMIA; IN-VIVO; VOLUME 7.5-PERCENT NACL; General & Internal Medicine; Science & Technology; SEVERE HEMORRHAGIC-SHOCK; NOREPINEPHRINE RELEASE; RAT MODEL; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

INTRODUCTION: 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). CONCLUSION: 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.