title: Intravenous injection of Albunex microspheres causes thromboxane mediated pulmonary hypertension in pigs, but not in monkeys or rabbits.
abstract: Intravenous injection of the ultrasound contrast agent Albunex (manufactured by Nycomed AS, Oslo, Norway; 400 million air-filled albumin microspheres per ml, mean diameter 4 +/- 1 microns) caused a dose-dependent increase of mean pulmonary arterial pressure in nine pigs. The highest dose (0.014 +/- 0.002 ml kg-1) increased mean pulmonary arterial pressure from 17 +/- 1 mmHg to 42 +/- 3 mmHg and decreased mean systemic arterial pressure from 111 +/- 9 to 93 +/- 12 mmHg. The pressure responses began 22 +/- 1 s after particle injection, and reached maximum after 51 +/- 3 s. No changes in mean pulmonary arterial pressure or mean systemic arterial pressure were observed after Albunex injections during treatment with indomethacin (10 mg kg-1 + 5 mg kg-1 h-1 i.v., n = 6) or the thromboxane A2 receptor antagonist HN-11500 (10 mg kg-1 + 5 mg kg-1 h-1 i.v., n = 3). No Doppler enhancement could be detected in a carotid artery following injection of 0.12 ml kg-1 Albunex during indomethacin treatment. In five rabbits, Albunex caused Doppler enhancement in a carotid artery, and 0.48 ml kg-1 did not affect mean pulmonary arterial pressure or other haemodynamic parameters in five rabbits or in three cynomolgus monkeys. The pressure response in pigs may be explained by release of thromboxane A2 from the pulmonary intravascular macrophages during phagocytosis of the microspheres. This response to Albunex was totally absent in rabbits and monkeys.
authors.affiliation: Nycomed AS Research and Development, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Ostensen
authors.forename: R
authors.initials: R
authors.lastname: Hede
authors.forename: Y
authors.initials: Y
authors.lastname: Myreng
authors.forename: T
authors.initials: T
authors.lastname: Ege
authors.forename: E
authors.initials: E
authors.lastname: Holtz
mesh_terms: D000418:Albumins / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008863:Microspheres; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D013045:Species Specificity; D013552:Swine; D013928:Thromboxane A2 / Q000502:physiology
chemical_list: D000418:Albumins; C060687:Albunex; D003287:Contrast Media; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D007213:Indomethacin