Acidosis inhibits rhythmic contractions of human thoracic ducts
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Acidosis inhibits rhythmic contractions of human thoracic ducts. / Møller, Anders L.; Hjortdal, Vibeke E; Boedtkjer, Donna M B; Boedtkjer, Ebbe.
I: Physiological Reports, Bind 7, Nr. 8, e14074, 2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Acidosis inhibits rhythmic contractions of human thoracic ducts
AU - Møller, Anders L.
AU - Hjortdal, Vibeke E
AU - Boedtkjer, Donna M B
AU - Boedtkjer, Ebbe
N1 - © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
PY - 2019
Y1 - 2019
N2 - Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid-base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery. Human thoracic ducts produce complex contractile patterns consisting of tonic rises in tension (isometric myography) or decreases in diameter (isobaric myography) with superimposed phasic contractions. Active tone development decreases substantially (~90% at 30 vs. 7 mmHg) at elevated transmural pressure. Acidosis inhibits spontaneous as well as noradrenaline- and serotonin-induced phasic contractions of human thoracic ducts by 70-90% at extracellular pH 6.8 compared to 7.4 with less pronounced effects observed at pH 7.1. Mean tension responses to noradrenaline and serotonin - averaged over the entire period of agonist exposure - decrease by ~50% at extracellular pH 6.8. Elevating extracellular [K+ ] from the normal resting level around 4 mmol/L increases overall tension development but reduces phasic activity to a level that is no different between human thoracic duct segments investigated at normal and low extracellular pH. In conclusion, we show that extracellular acidosis inhibits human thoracic duct contractions with more pronounced effects on phasic than tonic contractions. We propose that reduced phasic activity of lymph vessels at low pH attenuates lymph propulsion and increases the risk of edema formation.
AB - Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid-base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery. Human thoracic ducts produce complex contractile patterns consisting of tonic rises in tension (isometric myography) or decreases in diameter (isobaric myography) with superimposed phasic contractions. Active tone development decreases substantially (~90% at 30 vs. 7 mmHg) at elevated transmural pressure. Acidosis inhibits spontaneous as well as noradrenaline- and serotonin-induced phasic contractions of human thoracic ducts by 70-90% at extracellular pH 6.8 compared to 7.4 with less pronounced effects observed at pH 7.1. Mean tension responses to noradrenaline and serotonin - averaged over the entire period of agonist exposure - decrease by ~50% at extracellular pH 6.8. Elevating extracellular [K+ ] from the normal resting level around 4 mmol/L increases overall tension development but reduces phasic activity to a level that is no different between human thoracic duct segments investigated at normal and low extracellular pH. In conclusion, we show that extracellular acidosis inhibits human thoracic duct contractions with more pronounced effects on phasic than tonic contractions. We propose that reduced phasic activity of lymph vessels at low pH attenuates lymph propulsion and increases the risk of edema formation.
KW - Acidosis/physiopathology
KW - Adrenergic Agonists/pharmacology
KW - Aged
KW - Edema/physiopathology
KW - Epinephrine/pharmacology
KW - Female
KW - Humans
KW - Lymphatic Vessels/drug effects
KW - Male
KW - Middle Aged
KW - Muscle Contraction
KW - Muscle Tonus
KW - Muscle, Smooth/drug effects
KW - Periodicity
KW - Serotonin/pharmacology
KW - Serotonin Receptor Agonists/pharmacology
KW - Thorax/pathology
U2 - 10.14814/phy2.14074
DO - 10.14814/phy2.14074
M3 - Journal article
C2 - 31025551
VL - 7
JO - Physiological Reports
JF - Physiological Reports
SN - 2051-817X
IS - 8
M1 - e14074
ER -
ID: 241756051