Splanchnic artery occlusion (SAO) followed by release of the occlusive clamps produces circulatory
shock characterized by an abrupt
hypotension, cardiac depression and high lethality. We studied the effects of the
thromboxane receptor antagonist,
BM-13505, in rats during SAO
shock. Anesthetized rats subjected to total occlusion of the celiac and superior mesenteric arteries for 40 minutes developed a severe
shock state following reperfusion, usually resulting in death within 90-120 minutes of release of the occlusion.
BM-13505 was started at reperfusion for 10 minutes. SAO
shock rats treated with
BM-13505 (1 mg/kg) maintained post-reperfusion mean arterial blood pressure (MABP) at significantly higher values compared to those receiving only the vehicle (
0.9% NaCl). Treatment with
BM-13505 attenuated the plasma activity of the lysosomal
protease cathepsin D (p less than 0.05 from vehicle) and the plasma accumulation of free amino-
nitrogen compounds (p less than 0.01 from vehicle). Furthermore, the plasma activity of a
myocardial depressant factor was significantly lower in
BM-13505 treated rats than in non-treated rats (p less than 0.01 from vehicle). SAO
shock rats treated with
BM-13505 also exhibited a higher survival rate than the vehicle group (75% vs. 20%). These results suggest an important role of
thromboxane A2 in the pathophysiology of SAO
shock.