title: A selective beta2-adrenergic agonist, terbutaline, improves sepsis-induced diaphragmatic dysfunction in the rat.
abstract: BACKGROUND
  Sepsis causes diaphragmatic dysfunction, which can lead to the development of respiratory failure. We previously reported that isoproterenol, non-selective beta-adrenergic agonist, improved contractility of the diaphragm in a septic rat model. Since beta(2)-adrenoceptor agonists are widely used in the treatment of chronic respiratory disease, we investigated the effect of terbutaline, a selective beta(2)-adrenergic agonist, on contractility of the septic rat diaphragm and the contribution of intracellular Ca(2+) to the effect of terbutaline in vitro.
  
  
  METHODS
  Forty-eight rats were divided into a sham group (in which sham laparotomy was performed) and a CLP group (in which peritonitis was induced by cecal ligation and perforation). The left hemidiaphragm was removed at 16 h after the operation. The effect of terbutaline (10(-)(6) M) on contractility of the diaphragm was assessed by twitch characteristics (twitch tension, contraction time and contraction velocity) and force-frequency relationship. In addition, to investigate the role of calcium ions in the effect of terbutaline on contractility of the diaphragm, contractility of the diaphragm was assessed after the pre-incubation of the diaphragm with methoxy-verapamil (10(-)(5) M), Ca(2+)-free Krebs-Ringer's solution buffered with 2 mM of ethylene glycol tetra-acetic acid (EGTA), and ryanodine (10(-)(6) M).
  
  
  RESULTS
  Terbutaline significantly improved twitch characteristics and force-frequency relationship of the diaphragm in the CLP group (P<0.01). Incubation with methoxy-verapamil or calcium-free solution with EGTA did not show any changes in the inotropic effect of terbutaline in the CLP group. However, incubation with ryanodine completely abolished the inotropic effect of terbutaline in the CLP group.
  
  
  CONCLUSIONS
  The present study demonstrated that terbutaline increased contractility of the diaphragm in the septic rats. Since this inotropic effect was abolished by ryanodine administration, calcium release from the sarcoplasmic reticulum may contribute to the terbutaline-induced improvement in dysfunction of the septic diaphragm.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan. tetsu@sapmed.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ito
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Fujimura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Omote
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Namiki
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002432:Cecum / Q000502:physiology; D003964:Diaphragm / Q000503:physiopathology*; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007416:Intestinal Perforation / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D013726:Terbutaline / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D014665:Vasodilator Agents; D012433:Ryanodine; D005711:Gallopamil; D004533:Egtazic Acid; D013726:Terbutaline; D002118:Calcium