title: Pulmonary vasodilator response to adenosine triphosphate-sensitive potassium channel activation is attenuated during desflurane but preserved during sevoflurane anesthesia compared with the conscious state.
abstract: BACKGROUND
  The objective of this study was to investigate the effects of sevoflurane and desflurane anesthesia on the pulmonary vasodilator response to the adenosine triphosphate-sensitive potassium channel agonist, lemakalim, compared with the response measured in the conscious state. In addition, the authors assessed the extent to which sympathetic alpha1-adrenoreceptor inhibition and cyclooxygenase pathway inhibition modulate the vasodilator response to lemakalim.
  
  
  METHODS
  Twenty-four conditioned male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. After preconstriction with the thromboxane analogue, U46619, dose-response relationships to lemakalim were assessed on separate days in the conscious state and during sevoflurane (approximately 3.5% end-tidal) and desflurane (approximately 10.5% end-tidal) anesthesia (approximately 1.5 minimum alveolar concentration for each anesthetic agent). The effects of sympathetic alpha1-adrenoreceptor inhibition (prazosin) and cyclooxygenase inhibition (indomethacin) on the pulmonary vasodilator response to lemakalim also were assessed in the conscious and desflurane-anesthetized states.
  
  
  RESULTS
  Neither sevoflurane nor desflurane had a net effect on the baseline left pulmonary vascular pressure-flow relationship compared with the conscious state. The magnitude of the pulmonary vasodilator response to lemakalim was preserved during sevoflurane anesthesia but was attenuated (P < 0.05) during desflurane anesthesia compared with the conscious state. The attenuated lemakalim-induced vasodilator response during desflurane anesthesia was partially reversed (P < 0.05) by pretreatment with prazosin but not indomethacin.
  
  
  CONCLUSIONS
  These results indicate that adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation is preserved during sevoflurane anesthesia but is attenuated during desflurane anesthesia. The attenuated response to adenosine triphosphate-sensitive potassium channel activation during desflurane anesthesia is partially mediated by reflex sympathetic alpha1-adrenoreceptor vasoconstriction.
authors.affiliation: Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: U
authors.initials: U
authors.lastname: Kondo
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
mesh_terms: D000255:Adenosine Triphosphate; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D016292:Procedural Sedation; D019806:Cromakalim / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D000077335:Desflurane; D004285:Dogs; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists; D011651:Pulmonary Artery / Q000187:drug effects; D000077149:Sevoflurane; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D016861:Cyclooxygenase Inhibitors; D008738:Methyl Ethers; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D000077335:Desflurane; D007530:Isoflurane; D007213:Indomethacin