Effects of a selective
thromboxane synthetase inhibitor, (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic
acid hydrochloride monohydrate (OKY-046), were studied hemorheologically in
endotoxin shocked-rabbits. The animals were intravenously administrated with 0.1 mg of
endotoxin 3 times at intervals of 3 days. At 7 days after the last
endotoxin injection,
endotoxin (0.2 mg.kg(-1)) was intravenously administrated to induce a
shock.
OKY-046 (30 mg.kg(-1)) was administrated after
hypotension was developed by the
endotoxin treatment and, then, it was continuously injected at 0.03 mg.kg(-1).min(-1). Blood pressure remained unchanged and hypotensive was maintained during the treatment with
OKY-046. Blood was sampled from the femoral artery 15 (before the administration of
OKY-046), 45, and 120 minutes after the final administration of
endotoxin. Pa(O)(2) increased, and Pa(CO)(2), arterial pH, and base excess (BE) decreased during the
endotoxin shock. The decrease of pH and BE was prevented by the administration of
OKY-046. In the
endotoxin-shocked animals, hematocrit, whole blood viscosity, erythrocyte deformability, plasma fluidity, and the ratio of hematocrit to whole blood viscosity showed no significant differences between the
OKY-046 treated animals and non-treated ones. These data show that a selective
thromboxane synthetase inhibitor (OKY-046) does not improve the blood rheology during
endotoxin shock, although it seems to prevent the
acidosis in some extent.