title: Early potassium channel blockade improves sepsis-induced organ damage and cardiovascular dysfunction.
abstract: OBJECTIVE
  There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with potassium channels on development of sepsis.
  
  
  METHODS
  Sepsis was induced by caecal ligation and puncture (CLP) or sham surgery in Wistar rats. Four hours after surgery, animals received tetraethylammonium (TEA; a non-selective potassium channel blocker) or glibenclamide (a selective ATP-sensitive potassium channel blocker). Twenty-four hours after surgery, inflammatory, biochemical, haemodynamic parameters and survival were evaluated.
  
  
  RESULTS
  Sepsis significantly increased plasma NO(x) levels, expression of inducible nitric oxide synthase (NOS-2) protein in lung and thigh skeletal muscle, lung myeloperoxidase, urea, creatinine and lactate levels, TNF-α and IL-1β, hypotension and hyporesponsiveness to phenylephrine and hyperglycemia followed by hypoglycemia. TEA injected 4 h after surgery attenuated the increased NOS-2 expression, reduced plasma NO(x) , lung myeloperoxidase activity, levels of TNF-α and IL-1β, urea, creatinine and lactate levels, prevented development of hypotension and hyporesponsiveness to phenylephrine, the alterations in plasma glucose and reduced late mortality by 50%. Glibenclamide did not improve any of the measured parameters and increased mortality rate, probably due to worsening the hypoglycemic phase of sepsis.
  
  
  CONCLUSIONS
  Early blockade of TEA-sensitive (but not the ATP-sensitive subtype) potassium channels reduced organ damage and mortality in experimental sepsis. This beneficial effect seems to be, at least in part, due to reduction in NOS-2 expression.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, SC, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Sordi
authors.forename: D
authors.initials: D
authors.lastname: Fernandes
authors.forename: B T
authors.initials: BT
authors.lastname: Heckert
authors.forename: J
authors.initials: J
authors.lastname: Assreuy
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005905:Glyburide / Q000627:therapeutic use*; D006339:Heart Rate; D008136:Longevity; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*; D019789:Tetraethylammonium / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D019789:Tetraethylammonium; D052247:Nitric Oxide Synthase Type II; D005905:Glyburide