Antioxidants reverse reduction of the human hypoxic ventilatory response by subanesthetic isoflurane.
BACKGROUND
In subanesthetic concentrations, volatile anesthetics reduce the acute hypoxic response (AHR), presumably by a direct action on the carotid bodies but by an unknown molecular mechanism. To examine a possible involvement of reactive oxygen species or changes in redox state in this inhibiting effect, the authors studied the effect of antioxidants on the isoflurane-induced reduction of the AHR in humans.


METHODS
In 10 volunteers, the authors studied the effect of antioxidants (intravenous ascorbic acid and oral alpha-tocopherol) on the reduction by isoflurane (0.12% end-tidal concentration) of the AHR on a 3-min isocapnic hypoxic stimulus (hemoglobin oxygen saturation 86 +/- 4%). All subjects participated in three separate sessions in which the effects of the antioxidants (session 1), placebo (session 2), and sham isoflurane plus antioxidants (session 3) were tested on the (sham) isoflurane-induced effect on the AHR.


RESULTS
Isoflurane reduced the acute hypoxic response from 0.82 +/- 0.41 l . min . % to 0.49 +/- 0.23 l . min . % and from 0.89 +/- 0.43 l . min . % to 0.48 +/- 0.28 l . min . % in sessions 1 and 2, respectively (mean +/- SD; P < 0.05 vs. control). This reduction of the AHR was completely reversed by antioxidants (AHR = 0.76 +/- 0.39 l . min . %; not significantly different from control, session 1) but not by placebo in session 2 (AHR = 0.50 +/- 0.30 l . min . %; P < 005 vs. control). Sham isoflurane or antioxidants per se had no effect on the hypoxic response.


CONCLUSIONS
The data indicate that isoflurane may depress the AHR by influencing the redox state of oxygen-sensing elements in the carotid bodies. This finding may have clinical implications for patients who are prone to recurrent hypoxic episodes, e.g., due to upper airway obstruction, in the postoperative period when low-dose isoflurane may persist in the body for some time.
Teppema
Luc J
LJ
Department of Anesthesiology, Leiden University Medical Center, PO Box 9604, 2300 RC Leiden, The Netherlands. l.j.s.m.teppema@;umc.nl
Romberg
Raymonda R
RR
Dahan
Albert
A
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D007275:Injections, Intravenous; D007530:Isoflurane / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D000975:Antioxidants; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D014810:Vitamin E; D007530:Isoflurane; D001205:Ascorbic Acid; D010100:Oxygen