Persistency and pathway of isoflurane-induced inhibition of superoxide production by neutrophils.
BACKGROUND
Our previous work has demonstrated that treatment with isoflurane has a preconditioning-like inhibitory effect on superoxide production (SOP) by polymorphonuclear neutrophils. The current objectives were to determine persistency of this effect and to clarify where in the signalling pathway this inhibition of SOP occurred. The latter was accomplished using two receptor-dependent neutrophil agonists, platelet activating factor (PAF) and formyl-methionyl-leucyl-phenylalanine (fMLP), and two receptor-independent neutrophil stimuli, the protein-kinase C stimulator, phorbol myristate acetate (PMA), and the calcium ionophore, A23187.


METHODS
Arterial blood samples were obtained from eight dogs under baseline condition (conscious state), during isoflurane (1 MAC) administration, and 24 and 48 hr post-isoflurane (also in conscious state). Neutrophils were isolated and stimulated with 1 muM concentrations of PAF, fMLP, PMA, and A23187. SOP was measured spectrophotometrically.


RESULTS
Isoflurane administration caused (1) an approximate 50% decrease in SOP during PAF or fMLP (P < 0.01 vs baseline), which remained evident from 24 to 48 hr following isoflurane; (2) an initial 29% decrease in SOP during PMA (P < 0.05 vs baseline), which returned to baseline by 24 hr following isoflurane; and (3) no change in SOP during A23187 (P > 0.05 vs baseline).


CONCLUSIONS
Isoflurane administration caused prolonged (from 24 to 48 hr) decreases in agonist-induced SOP by neutrophils. This effect involved inhibition at site(s) in the signalling pathway upstream from protein kinase C. The current findings suggest that the intraoperative use of isoflurane may result in an extended impairment to the antibacterial host defense mechanism and that neutrophil inhibition may play a role in the delayed tissue protection afforded by treatment with volatile anesthetics.
Saad
Maged M
MM
Section of Cardiology, Advocate Illinois Masonic Medical Center, Chicago, IL, USA.
Eom
Woosik
W
Hu
Guochang
G
Kim
Song-Jung
SJ
Crystal
George J
GJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004285:Dogs; D007530:Isoflurane / Q000494:pharmacology* / Q000633:toxicity; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013053:Spectrophotometry; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D018685:Anesthetics, Inhalation; D010972:Platelet Activating Factor; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007530:Isoflurane; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate