Abstract
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.
Highlights
Peripheral edema – defined as tissue swelling due to interstitial fluid accumulation – is a frequent condition and significant complication of surgical interventions and commonly prescribed medications
We performed the time control experiments on matched thoracic duct segments investigated in parallel with – and experiencing similar time delays as – the segments exposed to acidosis
Metabolic acidosis was mimicked by reducing pHo and [HCO3–]o at constant pCO2, whereas respiratory acidosis was mimicked by reducing pHo and elevating pCO2 at constant [HCO3–]o
Summary
Peripheral edema – defined as tissue swelling due to interstitial fluid accumulation – is a frequent condition and significant complication of surgical interventions and commonly prescribed medications. From the lymphatic capillaries – that consist of only a single endothelial cell layer – the lymph collects in preand postnodal lymph vessels with a growing smooth muscle cell layer before it ends up in the larger lymph conduits including the thoracic duct (Margaris and Black 2012) This transport from the initial lymphatics toward the great veins typically moves the lymph against a steady-state pressure gradient and gravitational forces. Coordinated contractions and relaxations of neighboring lymphangions create the local transitory pressure differences that propel lymph from one lymphangion to the from the peripheral tissues in direction of the central inlet into the subclavian vein Consistent with this role for lymph pumping, spontaneous human thoracic duct contractions and responses to agonist stimulation are typically rhythmic and phasic more tonic contractions can occur in response to high agonist concentrations (Sjoberg and Steen 1991b; Telinius et al 2010). We propose that attenuated lymph vessel contractions during acidosis can contribute to local accumulation of interstitial fluid and manifest as edema
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