title: Intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction in humans.
abstract: OBJECTIVE
  Nicorandil has a hybrid property between nitrates and potassium channel openers and has been reported to cause a concentration-dependent relaxation of isolated guinea pig trachealis. Experimental asthma in a guinea pig model was also inhibited by nicorandil. However, no clinical data on the bronchorelaxant effects of this drug have been published. The aim of this study was to investigate whether intravenous nicorandil prevents thiamylal-fentanyl-induced bronchoconstriction.
  
  
  METHODS
  Double-blind, prospective, placebo-controlled, randomized study.
  
  
  METHODS
  A total of 36 patients were randomly allocated to two groups: a control group (n = 18) and a nicorandil group (n = 18).
  
  
  METHODS
  Intravenous administration of nicorandil or a placebo (normal saline).
  
  
  RESULTS
  Anesthesia was induced with 5 mg/kg thiamylal and 0.3 mg/kg vecuronium. A continuous infusion of 15 mg x kg(-1) x hr(-1) thiamylal was then used to maintain the anesthesia. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. At 20 mins after the induction of anesthesia, the control group patients were given a 6 mL/hr continuous infusion of normal saline and the nicorandil group patients were given a 6 mg x hr(-1) (6 mL/hr) continuous infusion of nicorandil for 60 mins. At 30 mins after the start of the study, both groups received a 5-microg/kg dose of fentanyl. Systolic and diastolic arterial pressure, heart rate, mean airway resistance, expiratory airway resistance, and dynamic lung compliance were measured for the baseline condition, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after the fentanyl injection (T36, T42, and T48) and 30 mins after the fentanyl injection (T60). Both groups had comparable baseline values for mean airway resistance, expiratory airway resistance, and dynamic lung compliance. In the control group, both mean airway resistance and expiratory airway resistance increased significantly at T36-60, compared with the baseline values, and dynamic lung compliance decreased significantly at T36-60, compared with the baseline value. In the nicorandil group, no changes in mean airway resistance, expiratory airway resistance, or dynamic lung compliance occurred at T36-60.
  
  
  CONCLUSIONS
  Our observations suggest that the intravenous administration of nicorandil has a bronchodilator effect in humans.
authors.affiliation: Department of Anesthesia, Chiba Hokusoh Hospital, Nippon Medical School, Inba-gun, Japan. HFB01245@nifty.com
authors.forename: Zen'ichiro
authors.initials: Z
authors.lastname: Wajima
authors.forename: Tatsusuke
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ogura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Imanaga
authors.forename: Toshiya
authors.initials: T
authors.lastname: Shiga
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Inoue
authors.forename: Ryo
authors.initials: R
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000037:antagonists & inhibitors*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020108:Nicorandil / Q000008:administration & dosage*; D011446:Prospective Studies; D013840:Thiamylal / Q000037:antagonists & inhibitors*
chemical_list: D018686:Anesthetics, Intravenous; D001993:Bronchodilator Agents; D013840:Thiamylal; D020108:Nicorandil; D005283:Fentanyl