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Leukotrienes, thromboxane A2, and prostaglandins during systemic anaphylaxis in sheep
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 1991-09, Vol.261 (3), p.H782-H792
Ort / Verlag
United States
Erscheinungsjahr
1991
Quelle
MEDLINE
Beschreibungen/Notizen
D. R. Morel, M. Skoskiewicz, D. R. Robinson, K. J. Bloch, D. C. Hoaglin and W. M. Zapol
Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
We investigated the roles of eicosanoid mediators in acute systemic
anaphylaxis in anesthetized sheep. Sheep were sensitized with
dinitrophenylated Ascaris suum extract and were challenged with an
intravenous injection of dinitrophenylated bovine serum albumin. During
anaphylaxis, cyclooxygenase inhibitors eliminated the elevation of arterial
plasma levels of thromboxane B2 and 6-ketoprostaglandin F 1 alpha but
markedly elevated the levels of leukotriene E4 in lung lymph without
significantly eliminating elevation of plasma levels of histamine. Most of
the measured physiological abnormalities accompanying anaphylaxis were
aggravated by cyclooxygenase blockade. Enhancement of this anaphylactic
mediator response was associated with an accentuated and prolonged increase
of airway pressure (P less than 0.05, compared with sensitized,
antigen-challenged but otherwise untreated sheep), a more intense hypoxemia
(P less than 0.0001), and leukopenia (P less than 0.001), changes that were
largely eliminated by pretreating with the sulfidopeptide leukotriene
(SPLT) antagonist FPL 55712, suggesting that the SPLTs were important
mediators of these responses. In contrast, the prolonged, but less severe,
systemic vascular collapse and the reduced pulmonary hypertension induced
by cyclooxygenase inhibitors were not influenced by the SPLT antagonist.
These results demonstrate that in sheep cyclooxygenase metabolites are
mainly involved in the acute, but transient, systemic and pulmonary
vascular response of systemic anaphylaxis, whereas SPLTs are primarily
implicated in the airway and secondary cardiovascular response. SPLT may
act either directly or by potentiating the release of and reactivity to
histamine and other mediators. Our data therefore suggest that a
combination of cyclooxygenase and lipoxygenase inhibition will be necessary
to more effectively protect against the consequences of an anaphylactic
reaction.