The myocardial depressant effect of volatile anesthetics does not involve arachidonic acid metabolites or pertussis toxin-sensitive G proteins.
The involvement of the phospholipid-arachidonic acid pathway and of a pertussis toxin-sensitive G protein in the myocardial depressant effect of volatile anesthetics was examined in the rat heart left papillary muscle and atria. Neither phospholipase A2, cyclooxygenase or lipoxygenase antagonists altered the potency or the efficacy of clinically used concentrations of halothane and isoflurane in decreasing the contractile force of the muscles. Pretreatment of rats with pertussis toxin (50 micrograms/kg i.v., 72 h before sacrifice), which abolished the myocardial depressant effect of muscarinic agonists, did not prevent the decrease in contractile force induced by the anesthetics. The results of this study indicate that the cellular mechanism of the myocardial depressant effect of volatile anesthetics does not involve a metabolite of the phospholipid-arachidonic acid pathway, does not require a functional pertussis toxin-sensitive G protein, and differs from that of muscarinic agonists.
Vulliemoz
Y
Y
Department of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000777:Anesthetics; D000889:Anti-Arrhythmia Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D002217:Carbachol; D007530:Isoflurane; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D006221:Halothane