Octreotide improves human lymphatic fluid transport a translational trial

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OBJECTIVES
Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage.

METHODS
Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg.

RESULTS
Pre-clinical: human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion.

CONCLUSIONS
Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.
OriginalsprogEngelsk
Artikelnummer380
TidsskriftEuropean Journal of Cardio-Thoracic Surgery
Vol/bind65
Udgave nummer1
Antal sider9
ISSN1010-7940
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The pre-clinical aspect of this study was funded by grants to DBB from the Aarhus University Research Foundation (AUFF-E-2015-FLS-8-68) and the Danish Research Council (DFF-4183-00333). The clinical aspect of this study was funded by a grant Novo Nordic Foundation (NNF17OC0029854).

Publisher Copyright:
# The Author(s) 2023.

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