The involvement of prostaglandins and thromboxanes in the response to pulmonary embolism in anaesthetized rabbits and isolated perfused lungs.
Embolisation of blood clots produced an increased pulmonary artery pressure in vitro and systemic hypotension in vivo. In control anaesthetized animals, systemic blood pressure fell by 44.9 +/- 28.0 mm Hg following embolisation and 40% of the animals died within 5 minutes of embolisation. Plasma concentrations of thromboxane B2 (TXB222222 2) and 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) were increased by 0.54 +/- 0.13 ng/ml and 0.41 +/- 0.25 ng/ml, respectively. Pretreatment of animals with aspirin (ASA), 5 mg/kg or 250 mg/kg, reduced the hypotensive response and the TXB 2 and 6-keto-PGF 1 alpha release. Embolisation of isolated lungs perfused with blood-free medium induced an increase in pulmonary artery pressure of 32.7 +/- 21.0 mm Hg and significantly increased the content of TXB 2 and 6-keto-PGF 1 alpha in the perfusate. Pretreatment of lungs with indomethacin, 10 micrograms/ml, reduced the mean pulmonary pressure response to embolisation to 10.6 +/- 4.9 mm Hg and blocked the appearance of TXB 2 in the perfusate. Embolisation with an agarose clot induced only a 2.58 +/- 0.8 mm Hg increase in pressure and no detectable TXB 2 release. These results indicate that embolisation of lungs with a blood clot induces the release of TXB 2 and 6-keto-PGF 1 alpha. The release of these mediators, the hemodynamic responses and mortality were blocked by ASA pretreatment.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000768:Anesthesia, General; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D007022:Hypotension / Q000209:etiology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011312:Pressure; D011651:Pulmonary Artery; D011655:Pulmonary Embolism / Q000150:complications / Q000378:metabolism*; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin; D007213:Indomethacin