RESUMO
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.
Assuntos
Quilotórax , Vasos Linfáticos , Adulto , Humanos , Octreotida/farmacologia , Octreotida/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Estudos Cross-OverRESUMO
Protein-losing enteropathy (PLE) is a severe Fontan complication. This is a case report of the first hybrid treatment of PLE in Denmark of an 11-year-old Fontan patient with severe symptoms (diarrhoea, fatigue and swelling) and low albumin level. Diagnostics included intranodal and intrahepatic dynamic contrast magnetic resonance lymphangiography. The hybrid intervention consisted of selective lymphatic duct embolisation and innominate vein turn-down to treat PLE. The interventions went well, and two months after discharge the patient was relieved from PLE symptoms, the albumin level was normalised, and the patient felt more energetic.
Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Enteropatias Perdedoras de Proteínas , Albuminas , Criança , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/complicações , Humanos , Complicações Pós-Operatórias/etiologia , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/etiologia , Enteropatias Perdedoras de Proteínas/terapiaRESUMO
The lymphatic system is compromised in different groups of patients. To recognize pathology, we must know what is healthy. We use Near-Infrared Fluorescence (NIRF) to assess peripheral lymphatic function in humans. We have shown that external factors such as exercise, hyperthermia, and pharmacological mediators influence the function of peripheral lymphatic vessels. In this study, we explored the impact on lymphatic vessels by the ever-present external factor-gravity. We used NIRF imaging to investigate the lymphatic changes to gravity. Gravity was assessed by changing body position from supine to standing. We extracted following lymphatic functional parameters: lymphatic packet propulsion frequency (contractions/min), velocity (cm/s), and pressure (mmHg). Raw data analysis was performed using a custom-written Labview program. All sequences were analyzed by two observers and interclass correlation scores were calculated. All statistical analysis was performed using RStudio Team (2021). RStudio: Integrated Development Environment for R. RStudio, PBC. Healthy participants (n = 17, 11 males, age 28.1 ± 2.6 years) were included. The lymphatic packet propulsion frequency at baseline was 0.5 ± 0.2 contractions/min and rose within 3 min significantly to a maximum of 1.2 ± 0.5 contractions/min during upright posture and remained significantly higher than the baseline lymphatic packet propulsion frequency after lying down again for up to 6 min. The lymph velocity was 1.5 ± 0.4 cm/s at baseline and changed in both directions and without a specific pattern at different points in time during standing. Lymph pressure was significantly higher while standing (mean increase 9 mmHg, CI: 2-15 mmHg). The ICC scores were 89.8% (85.9%-92.7%), 59.3% (46.6%-69.6%) and 89.4% (79.0%-94.8%) in lymphatic packet propulsion frequency (130 observations), velocity (125 observations), and pressure (30 observations), respectively. The lymphatic system responds within few minutes to gravitational changes by increasing lymphatic packet propulsion frequency and pressure.