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Scintigraphic In Vivo Assessment of the Development of Pulmonary Intravascular Macrophages in Liver Disease^*

Experimental Study in Rats With Biliary Cirrhosis

^* From INSERM U484 (Dr. Miot-Noirault), Clermont-Ferrand Cédex; INSERM U316/EMI U0010 (Drs. Montharu and Le Pape), Tours; and MDS Pharma Services Europe (Drs. Faure and Guichard), Lyon, France.

Correspondence to: Elisabeth Miot-Noirault, PhD, INSERM U484, BP 184, Rue Montalembert, 63005 Clermont Ferrand Cédex, France; e-mail: noirault{at}inserm484.u-clermont1.fr

Study objectives: In regard to nuclear medicine literature reporting lung uptake of colloidal radiopharmaceuticals in patients with liver diseases, it has been hypothesized that liver abnormalities could trigger induction of pulmonary intravascular macrophages (PIMs) in humans normally lacking them. Recently, experimental induction of PIMs in rats in which they are not normally prevalent has been demonstrated to be at the origin of pulmonary hemodynamic alterations with an increased susceptibility to ARDS. If such induction may occur in humans, the risk of pulmonary hemodynamic alterations has to be considered and detected. This study demonstrates in a rodent model of biliary cirrhosis that scintigraphy of phagocytic function as commonly used for liver exploration is a suitable strategy for staging PIM development.

Design: Sixty rats were randomized as follows: bile duct section (n = 40), sham operation (n = 10), and no operation (n = 10). The rats were submitted to scintigraphy of phagocytic function every 5 days over 35 days for the assessment of radiocolloid uptake within lung and liver. At day 35, radioactivity of blood was counted and immunohistochemistry was performed on lung specimens.

Results: As disease progressed, radiopharmaceutical uptake decreased within the liver, while increasing considerably in the lung. At day 35, lung uptake averaged about 66% as compared to 3% before surgery. Lung histologic findings revealed numerous intravascular mononuclear cells closely related to the monocyte-macrophage lineage.

Conclusion: Scintigraphy of phagocytic function commonly used for liver scanning could be a suitable strategy for the diagnosis of the induction of PIMs under pathologic situations.

Key Words: biliary cirrhosis • pulmonary intravascular macrophages • pulmonary phagocytosis • rat • scintigraphy

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