TY - JOUR

T1 - Octreotide improves human lymphatic fluid transport a translational trial

AU - Holm-Weber, Thomas

AU - Skov, Frederik

AU - Mohanakumar, Sheyanth

AU - Thorup, Lene

AU - Riis, Troels

AU - Christensen, Mikkel Bring

AU - Sonne, David Peick

AU - Jensen, Per Bo

AU - Bødtkjer, Donna Briggs

AU - Hjortdal, Vibeke Elisabeth

N1 - Publisher Copyright: # The Author(s) 2023.

PY - 2024

Y1 - 2024

N2 - 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 ¼ 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 ¼ 0.36). Plethysmography revealed similar capillary filtration coefficients (P ¼ 0.057), but almost a doubling of the isovolumetric pressures (P ¼ 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.

AB - 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 ¼ 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 ¼ 0.36). Plethysmography revealed similar capillary filtration coefficients (P ¼ 0.057), but almost a doubling of the isovolumetric pressures (P ¼ 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.

KW - Chylothorax

KW - Clinical study

KW - Lymphatic

KW - Near-infrared fluorescence imaging

KW - Octreotide

KW - Randomized cross-over study

U2 - 10.1093/ejcts/ezad380

DO - 10.1093/ejcts/ezad380

M3 - Journal article

C2 - 37951584

AN - SCOPUS:85183994184

VL - 65

JO - European Journal of Cardio-thoracic Surgery

JF - European Journal of Cardio-thoracic Surgery

SN - 1010-7940

IS - 1

M1 - 380

ER -