Inhibition of thromboxane synthesis reduces endotoxin-induced right ventricular failure in sheep.
METHODS
There is a marked decrease of the right ventricular ejection fraction after the administration of a bolus of endotoxin to sheep. This hemodynamic response may be the result of thromboxane-mediated pulmonary hypertension. Right ventricular function was studied in an ovine model after the administration of endotoxin (1 microgram/kg Escherichia coli) with and without pretreatment with OKY-046, a selective thromboxane synthetase inhibitor.


RESULTS
OKY-046 attenuated the endotoxin-induced increase in pulmonary arterial pressure and prevented the early decreases in right ventricular ejection fraction and cardiac output. However, thromboxane synthetase inhibition failed to prevent endotoxin-induced hypoxemia. The marked increase in plasma thromboxane concentrations, which is usually seen after the administration of endotoxin, was prevented by pretreating the animals with OKY-046. On the other hand, increased plasma prostacyclin concentrations were observed in sheep treated with the thromboxane synthetase inhibitor.


CONCLUSIONS
This series of experiments shows that the early endotoxin-induced decrease in right ventricular ejection fraction can be alleviated by the application of OKY-046.
Redl
G
G
Department of Anesthesiology, University of Texas Medical Branch, Galveston.
Abdi
S
S
Traber
L D
LD
Nichols
R J
RJ
Flynn
J T
JT
Herndon
D N
DN
Traber
D L
DL
D000818:Animals; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004926:Escherichia coli; D006333:Heart Failure / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects*; D008689:Methacrylates / Q000494:pharmacology*; D010101:Oxygen Consumption; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004731:Endotoxins; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel