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10.1128/CVI.00390-16

http://scihub22266oqcxt.onion/10.1128/CVI.00390-16
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suck abstract from ncbi


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pmid27581435
      Clin+Vaccine+Immunol 2016 ; 23 (11 ): 863-872
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  • Small-Volume Adenosine, Lidocaine, and Mg2+ 4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics #MMPMID27581435
  • Griffin MJ ; Letson HL ; Dobson GP
  • Clin Vaccine Immunol 2016[Nov]; 23 (11 ): 863-872 PMID27581435 show ga
  • Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg(2+) (ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1?, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1?, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.
  • |Acidosis/etiology/immunology/microbiology [MESH]
  • |Adenosine/*administration & dosage/therapeutic use [MESH]
  • |Animals [MESH]
  • |Anti-Bacterial Agents/administration & dosage/therapeutic use [MESH]
  • |C-Reactive Protein/analysis [MESH]
  • |Cytokines/biosynthesis/immunology [MESH]
  • |Disease Models, Animal [MESH]
  • |Drug Therapy, Combination [MESH]
  • |Edema/immunology/microbiology [MESH]
  • |Hyperkalemia/etiology/immunology/microbiology [MESH]
  • |Infusions, Intravenous [MESH]
  • |Interleukin-1beta/blood [MESH]
  • |Interleukin-6/blood [MESH]
  • |Lidocaine/*administration & dosage/therapeutic use [MESH]
  • |Magnesium Sulfate/*administration & dosage/therapeutic use [MESH]
  • |Male [MESH]
  • |Rats [MESH]


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