title: Low-Dose Sodium Nitrite Fluid Resuscitation Prevents Lethality From Crush Syndrome by Improving Nitric Oxide Consumption and Preventing Myoglobin Cytotoxicity in Kidney in A Rat Model.
abstract: Crush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from pressure. CS has a high mortality, even when patients receive fluid therapy. We examined whether administration of NaNO2-containing fluid can improve survival in a rat model of CS.
  
  
  
  The CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into six groups: sham; CS with no treatment; CS with normal saline treatment; CS with normal saline + 25 mEq/L bicarbonate treatment; and CS with normal saline + 200 or 500 μmol/kg NaNO2.
  
  
  
  Blood and tissue samples were collected for histological and biochemical analyses at predetermined time points before and after reperfusion. Ischemic compression of rat hind limbs reduced nitrite content in the crushed muscle, and subsequent reperfusion resulted in reactive oxygen species-induced circulatory dysfunction and systemic inflammation. Rats treated with 200 μmol/kg NaNO2 showed increased nitric oxide (NO) levels, blood circulation, and neoangiogenesis, decreased generation of reactive oxygen species, and suppression of the inflammatory response, leading to complete recovery.
  
  
  
  Treatment with 200 μmol/kg NaNO2 prevents muscle damage induced by ischemia reperfusion via the protective effects of NO and suppression of systemic inflammation, thereby increasing survival rates in CS.
authors.affiliation: *Laboratory of Drug Safety Management, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan †Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Murata
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyake
authors.forename: Naomi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Ryuta
authors.initials: R
authors.lastname: Suzuki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Inoue
authors.forename: Jun
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kanamoto
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D015153:Blotting, Western; D003444:Crush Syndrome / Q000378:metabolism* / Q000628:therapy*; D005440:Fluid Therapy / Q000379:methods*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009211:Myoglobin / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D009211:Myoglobin; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D012977:Sodium Nitrite