title: [Exogenous nitric oxide donor in the liver inflammatory and hemodynamic response after hemorrhagic shock].
abstract: BACKGROUND
  Hemorrhagic shock (HS) results in oxidative stress to cells and in the induction of the inflammatory response, with an increased expression of a number of proinflammatory mediators and cytokines. We tested the ability of the nitric oxide (NO) donor sodium nitroprusside (NP) to reduce tissue injury in a rodent model of uncontrolled hemorrhagic shock.
  
  
  METHODS
  Seventy two Sprague Dawley rats weighing 250-300 g were subjected to a model of uncontrolled hemorrhagic shock. Four groups of animals were included (n = 18 per group): sham/saline, sham/NP, shock/saline, shock/NP. Experimental design consisted of the development of hemorrhagic shock (3 ml/100 g) in a 15-min period, tail amputation (75%) and drug administration at 30 min, fluid resuscitation (FR) with Ringer's lactate (RL) solution to reach a mean arterial pressure (MAP) of 40 mmHg, a hospital phase of 60 min with hemostasis and FR with LR solution to reach a MAP of 70 mmHg, and a 3-day observation phase. Treatment at the beginning of resuscitation included either normal saline (groups 1, 3) or NP (0.5 mg/kg) (groups 2, 4). The following parameters were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase (MPO), liver histology, and 3-day survival.
  
  
  RESULTS
  NP significantly reduced fluid requirements for resuscitation (p = 0.0001). We also observed an improved statistically significant difference in tests demonstrating hepatic injury (p = 0.0001), neutrophil infiltration as evidences by liver MPO (p <0.05), and histology studies (p = 0.001). Survival was also increased from 40% in controls to 60% with NP treatment.
  
  
  CONCLUSIONS
  These data suggest that excess NO mediates hemorrhage-induced liver injury, and that the suppression of NO with NP may reduce the pathological consequences of severe hemorrhage, possibly by scavenging superoxide (O(2)(-)), thus limiting the production of more aggressive radicals.
authors.affiliation: Dirección de Educación e Investigación en Salud, Unidad Médica de Alta Especialidad, Hospital de Ginecoobstetricia, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco. robana@prodigy.net.mx
authors.forename: Roberto
authors.initials: R
authors.lastname: Anaya-Prado
authors.forename: Luis H
authors.initials: LH
authors.lastname: Toledo-Pereyra
authors.forename: Ren-Feng
authors.initials: RF
authors.lastname: Guo
authors.forename: Jayne
authors.initials: J
authors.lastname: Reuben
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D005440:Fluid Therapy; D006505:Hepatitis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007552:Isotonic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D009336:Necrosis; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D009599:Nitroprusside / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012151:Resuscitation; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method
chemical_list: D007552:Isotonic Solutions; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D000077325:Ringer's Lactate; D009599:Nitroprusside; D009569:Nitric Oxide; D009195:Peroxidase