Characterization and mechanism of side-effects of Oxygent HT (highly concentrated fluorocarbon emulsion) in swine.
Perfluorooctyl bromide is an oxygen-carrying perfluorocarbon presently under development as an artificial blood substitute (Oxygent HT). Intravenous (i.v.) Oxygent HT elicits a mild side-effect profile in man characterized by early onset headache and nausea and delayed onset fever. Early onset flushing has also been observed. Species of Artiodactyla are sensitive to particulate injections and demonstrate a transient pulmonary hypertensive response thought to be associated with the large number of pulmonary intravascular macrophages found in these species. Because of this sensitivity, we chose the swine as a model for further investigations. In anesthetized and conscious swine, i.v. Oxygent HT transiently increased mean pulmonary artery pressure (mPAP) and caused flushing. Both effects peaked at 30 min post injection and were resolved by 2 hrs. Plasma thromboxane B2 (TxB) increased in response to Oxygent HT. Oxygent HT-induced changes in mPAP, flush, and plasma TxB were blocked by aspirin and ibuprofen. Dexamethasone and SQ 29,548 (thromboxane receptor antagonist) blocked the mPAP increase. In conscious swine, Oxygent HT caused a febrile response which was blocked by ibuprofen or dexamethasone. Thus, both early- and late-onset effects of Oxygent HT in swine are blocked by interference with the arachidonic acid cascade. These findings suggest that the 2-phase "flu-like" syndrome induced by Oxygent HT is secondary to the release of products of the arachidonic acid cascade and may be effectively prophylaxed in man with corticosteroids or long plasma half-life cyclooxygenase inhibitors.
Alliance Pharmaceutical Corp., San Diego, CA 92121.
S F
SF
Flaim
D R
DR
Hazard
J
J
Hogan
R M
RM
Peters
D000818:Animals; D001802:Blood Substitutes / Q000009:adverse effects*; D003907:Dexamethasone / Q000494:pharmacology; D004655:Emulsions; D005466:Fluorocarbons / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006842:Hydrocarbons, Brominated; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects; D011749:Pyrogens / Q000037:antagonists & inhibitors; D013552:Swine
D001802:Blood Substitutes; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D011749:Pyrogens; D003907:Dexamethasone; C003072:perflubron; D007052:Ibuprofen; D007213:Indomethacin