title: Guanylate cyclase inhibition by methylene blue in circulatory shock caused by acute necrotizing pancreatitis: a word of caution based on a porcine model.
abstract: OBJECTIVE
  To study the therapeutic application of guanylate cyclase inhibition by methylene blue in an experimental model of acute pancreatitis in pigs.
  
  
  METHODS
  acute necrotizing pancreatitis was induced in anesthetized pigs by the retrograde infusion of 1 ml/kg of 5% sodium taurocholate and 8 U/kg enterokinase in the pancreatic duct. Three groups were studied (n = 5): control (C), pancreatitis (AP), and MB bolus followed by pancreatitis (MB+P). The data included serum and abdominal fluid enzymes, hemodynamic variables, arterial hemogasometry, abdominal fluid volume, inflammatory markers, plasma nitrite/nitrate (NOx), plasma myeloperoxidase (MPO) and plasma malondialdehyde (MDA). One- and two-way analysis of variance (ANOVA) was performed, followed by the Bonferroni test (p < 0.05).
  
  
  RESULTS
  amylase and lipase were three and 10-fold higher in the AP group. Myeloperoxidase activity was 50% higher in the AP group. The hemodynamic data indicated early hypovolemic shock followed by cardiogenic shock. Severe fluid translocation to the peritoneal cavity was observed. Plasma NOx remained unchanged. The MB+P group had a five-fold increase in MDA compared with the C group.
  
  
  CONCLUSIONS
  preemptive application of MB in pigs with AP demonstrated no significant effects on hemodynamic and inflammatory variables. The use of MB is inadequate in cases of exponential NO release, and extreme caution must be exercised, given the increase in lipid peroxidation based on the malondialdehyde dosage.
authors.forename: Caroline Floreoto
authors.initials: CF
authors.lastname: Baldo
authors.forename: Verena Kise
authors.initials: VK
authors.lastname: Capellini
authors.forename: Andrea Carla
authors.initials: AC
authors.lastname: Celotto
authors.forename: Fabiane
authors.initials: F
authors.lastname: Sônego
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Tirapelli
authors.forename: Marcelo
authors.initials: M
authors.lastname: Batalhão
authors.forename: Evelin Capellari
authors.initials: EC
authors.lastname: Cárnio
authors.forename: José Sebastião
authors.initials: JS
authors.lastname: dos Santos
authors.forename: Paulo Roberto Barbosa
authors.initials: PR
authors.lastname: Evora
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D008751:Methylene Blue / Q000494:pharmacology / Q000627:therapeutic use*; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000201:enzymology; D012770:Shock, Cardiogenic / Q000188:drug therapy* / Q000209:etiology*; D013552:Swine
chemical_list: D006162:Guanylate Cyclase; D008751:Methylene Blue