Intravenous injection of Albunex^R 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.

Liquid ventilation with perfluorocarbons facilitates resumption of spontaneous circulation in a swine cardiac arrest model

“…The same process may be occurring in the swine when exposed to PFC resulting in an inflammatory response in the microvasculature resulting in acute lung injury. [22][23][24] Recent preliminary experiments in our laboratory have utilized another PFC (Perflutel RM 101, Miteni, Milan, Italy). This PFC is compatible with biologic use and was utilized in small animal models (rabbits) of TLV by Tissier et al 8 where it did not cause lung toxicity.…”

SURF imaging: In vivo demonstration of an ultrasound contrast agent detection technique

“…Sonovue (Bracco, Milan, Italy) was injected as a 1-mL bolus via a peripheral vein in the left ear. To prevent the pigs from experiencing thromboxanemediated pulmonary hypertension, they were treated with indomethacin as described by Østensen et al [19].…”

Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: A feasibility study in pigs

“…Østensen et al [33] also reported the accumulation of intravenously injected particulate material in the lungs of pigs, leading to acute pulmonary hypertension and systemic hypotension. This was not observed following intravenous injection in rabbits, monkeys or man, and was presumed to be a species specific effect.…”