Pentobarbital augments pulmonary vasoconstrictor response to cyclooxygenase inhibition.
We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of pentobarbital sodium anesthesia on regulation of the pulmonary circulation by endogenous metabolites of the cyclooxygenase pathway. Our specific objective was to characterize the effects of two chemically dissimilar inhibitors of the cyclooxygenase pathway, indomethacin and sodium meclofenamate, on the pulmonary vascular P/Q relationship measured in conscious and pentobarbital-anesthetized dogs. P/Q plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Controlled ventilation during pentobarbital anesthesia (30 mg/kg iv) allowed the matching of systemic arterial and mixed venous blood gases to conscious values. Pentobarbital had no net effect on the base-line P/Q relationship compared with that measured in conscious dogs. Cyclooxygenase pathway inhibition with either indomethacin (5 mg/kg iv) or meclofenamate (2.5 mg/kg iv) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) in both conscious and pentobarbital-anesthetized dogs. However, the magnitude of the pulmonary vasoconstrictor response to indomethacin was increased (P less than 0.05) over a broad range of Q, and the pulmonary vasoconstrictor response to meclofenamate was increased (P less than 0.05) over the entire range of Q in pentobarbital-anesthetized compared with conscious dogs. Thus regulation of the base-line pulmonary vascular P/Q relationship by endogenous metabolites of the cyclooxygenase pathway in conscious dogs is altered during pentobarbital anesthesia.
Nyhan
D P
DP
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Chen
B B
BB
Fehr
D M
DM
Goll
H M
HM
Murray
P A
PA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D008469:Meclofenamic Acid / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010424:Pentobarbital / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D062367:ortho-Aminobenzoates; D002245:Carbon Dioxide; D008469:Meclofenamic Acid; D010424:Pentobarbital; D010100:Oxygen; D007213:Indomethacin