title: Attenuated hypoxic pulmonary vasoconstriction during isoflurane anesthesia is abolished by cyclooxygenase inhibition in chronically instrumented dogs.
abstract: BACKGROUND
  Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism whereby gas exchange is improved through the diversion of blood flow away from poorly oxygenated regions of the lung. The effect of isoflurane anesthesia on HPV is unclear. Using a chronically instrumented canine model, it was hypothesized that isoflurane anesthesia would attenuate HPV compared to the response measured in the same animal in the conscious state. Moreover, because volatile anesthetics increase the production of cyclooxygenase metabolites, it was hypothesized that attenuation of HPV during isoflurane anesthesia would be abolished by cyclooxygenase inhibition.
  
  
  METHODS
  Left pulmonary vascular pressure-flow plots were generated in chronically instrumented dose by measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during inflation of a hydraulic occluder implanted around the right main pulmonary artery. In protocol 1 (n - 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (systemic arterial PO2 approximately 50 mmHg) in the conscious and isoflurane-anesthetized states. In protocol 2 (n = 7), left pulmonary vascular pressure-flow plots were generated during normoxia and hypoxia (1) in the conscious state, (2) in the conscious state after inhibition of the cyclooxygenase pathway with indomethacin, and (3) during isoflurane anesthesia after cyclooxygenase inhibition.
  
  
  RESULTS
  In both the conscious and isoflurane-anesthetized states, the magnitude of HPV was dependent on the level of left pulmonary blood flow. Compared to the response measured in the conscious state, the magnitude of HPV was attenuated during isoflurane anesthesia over the empirically measured range of left pulmonary blood flow. Cyclooxygenase inhibition abolished the isoflurane-induced attenuation of HPV.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that isoflurane anesthesia attenuates the magnitude of HPV compared to the response measured in the same animal in the conscious state. Cyclooxygenase inhibition potentiated the magnitude of HPV in both the conscious and isoflurane-anesthetized states, which indicates that vasodilator metabolites of the cyclooxygenase pathways modulate HPV under these conditions. Importantly, the finding that the magnitude of HPV is flow-dependent in both the conscious and isoflurane-anesthetized states may explain conflicting reports in the literature concerning the effects of isoflurane anesthesia on the HPV response.
authors.affiliation: Department of Anesthesiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Lennon
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007530:Isoflurane / Q000633:toxicity*; D008168:Lung / Q000098:blood supply*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D016861:Cyclooxygenase Inhibitors; D007530:Isoflurane; D007213:Indomethacin