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Octreotide - The Lymphatic Stimulator?

Presented By:

T. Holm-Weber, F. Skov, L. Thorup, S. Mohanakumar, T. Riis, P. Jensen, M. Christensen, D. Sonne, D. Briggs, V. Hjortdal.

Rigshospitalet

thomas.holm-weber@regionh.dk

Overview:

Objective: Chylothorax is a troublesome condition. Octreotide is used off-label to facilitate chylothorax resolution in pediatric and adult patients. The mode of action to alleviate chylothorax for octreotide is unclear: lowered lymph production is speculated to be involved. In this study we explore whether octreotide has a direct pharmacodynamic effect upon human lymphatic vessels in a pre-clinical and in a clinical setup.

Methods:
Pre-clinical: human lymphatic vessels were mounted in a myograph. The effect of octreotide on force generation was assessed during acute and prolonged drug incubation.

Clinical: Double-blinded, randomised cross-over study. Participants were intravenously infused with octreotide or saline. During infusion, Near-Infrared Fluorescence Imaging was used to examine the effect of octreotide on lymph rate and pressure. Plethysmography was performed to extract capillary filtration rate, capillary filtration coefficient and isovolumetric pressures. 

Results:
Pre-clinical: Human thoracic duct (n = 27) smooth muscle cell contraction rate was stimulated during acute and prolonged exposure to octreotide in a dose dependent way with a maximum effect at 10 and 100 nmol/L.

Clinical: Healthy adults (n = 16) displayed no changes in lymph rate (p = 0.37) nor lymph pressure between the study dates (p-value = 0.36). Plethysmography revealed similar capillary filtration coefficients (p = 0.06) but almost doubling of the isovolumetric pressures (p = 0.0045). 

Conclusion: Octreotide increased lymphatic contractility in the pre-clinical setup but had no effect on lymphatic rate or pressure. Plethysmography revealed an increase in lymphatic drainage at higher afterload. Our study suggests that octreotide increases the lymphatic capacity.