Lymphedema, a disfiguring condition characterized by an asymmetrical swelling of the limbs, is suspected to be caused by dysfunctions in the lymphatic system. A possible source of lymphatic dysfunction is the reduced mechanosensitivity of lymphangions, the spontaneously contracting units of the lymphatic system. In this study, the entrainment of lymphangions to an oscillatory wall shear stress (OWSS) is characterized in rat thoracic ducts in relation to their shear sensitivity. The critical shear stress above which the thoracic ducts show a substantial inhibition of contraction was found to be significantly negatively correlated to the diameter of the lymphangion. The entrainment of the lymphangion to an applied OWSS was found to be significantly dependent on the difference between the applied frequency and the intrinsic frequency of contraction of the lymphangion. The strength of the entrainment was also positively correlated to the applied shear stress when the applied shear was less than the critical shear stress of the vessel. The ejection fraction and fractional pump flow were also affected by the difference between the frequency of the applied OWSS and the vessel's intrinsic contraction frequency. The results suggest an adaptation of the lymphangion contractility to the existing oscillatory shear stress as a function of its intrinsic contractility and shear sensitivity. These adaptations might be crucial to ensure synchronized contraction of lymphangions through mechanosensitive means and might help explain the lymphatic dysfunctions that result from impaired mechanosensitivity.
We present the first Lymphatic injury can alter collecting lymphatic contractility, but not much is known about how its mechanosensitivity to external pressure is affected, which is crucial given the current pressure application methods for treating lymphoedema. We show that oscillatory pressure waves (OPW), akin to intermittent pneumatic compression (IPC) therapy, optimally entrain lymphatic contractility and modulate function depending on the frequency and propagation speed of the OPW. We show that the OPW‐induced entrainment and contractile function in the intact collecting lymphatics are enhanced 28 days after a contralateral lymphatic ligation surgery. The results show that IPC efficacy can be improved through proper selection of OPW parameters, and that collecting lymphatics adapt their function and mechanosensitivity after a contralateral injury, switching their behaviour to a pump‐like configuration that may be more suited to the altered microenvironment.
We present the first
Lymphatic injury can alter collecting lymphatic contractility, but not much is known about how its mechanosensitivity to external pressure is affected, which is crucial given the current pressure application methods for treating lymphoedema.
We show that oscillatory pressure waves (OPW), akin to intermittent pneumatic compression (IPC) therapy, optimally entrain lymphatic contractility and modulate function depending on the frequency and propagation speed of the OPW.
We show that the OPW‐induced entrainment and contractile function in the intact collecting lymphatics are enhanced 28 days after a contralateral lymphatic ligation surgery.
The results show that IPC efficacy can be improved through proper selection of OPW parameters, and that collecting lymphatics adapt their function and mechanosensitivity after a contralateral injury, switching their behaviour to a pump‐like configuration that may be more suited to the altered microenvironment.
Intermittent pneumatic compression (IPC) is commonly used to control the swelling due to lymphoedema, possibly modulating the collecting lymphatic function. Lymphoedema causes lymphatic contractile dysfunction, but the consequent alterations in the mechanosensitivity of lymphatics to IPC is not known. In the present work, the spatiotemporally varying oscillatory pressure waves (OPW) generated during IPC were simulated to study the modulation of lymphatic function by OPW under physiological and pathological conditions. OPW with three temporal frequencies and three propagation speeds were applied to rat tail collecting lymphatics. The entrainment of the lymphatics to OPW was significantly higher at a frequency of 0.05 Hz compared with 0.1 Hz and 0.2 Hz (
- NSF-PAR ID:
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- Date Published:
- Journal Name:
- The Journal of Physiology
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- p. 2699-2721
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Skeletal muscle's isometric contractile properties represent one of the classic structure–function relationships in all of biology and allow scaling single fibre mechanical properties to whole muscle properties based on the muscle's architecture.
This physiological relationship has only been validated in small animals but is often extrapolated to human muscles, which are orders of magnitude larger.
We leverage a unique surgical technique in which a human gracilis muscle is transplanted from the thigh to the arm to restore elbow flexion after brachial plexus injury, aiming to directly measure muscles properties
in situand test directly the architectural scaling predictions.
Using these direct measurements, we establish human muscle fibre‐specific tension of ∼170 kPa.
Furthermore, we show that the gracilis muscle actually functions as a muscle with relatively short fibres acting in parallel
vs. long fibres as previously assumed based on traditional anatomical models.
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We used rat models of HFpEF and HFrEF to reveal distinct differences in intracellular calcium regulation and excitation‐contraction (EC) coupling.
While HFrEF is characterized by defective EC coupling at baseline, HFpEF exhibits enhanced coupling fidelity, further aggravated by a reduction in β‐adrenergic sensitivity.
These differences in EC coupling and β‐adrenergic sensitivity may help explain why therapies that work in HFrEF are ineffective in HFpEF.
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We identified that lipin1 mRNA expression levels are significantly reduced in skeletal muscles of Duchenne muscular dystrophy patients and mdx mice.
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New Findings What is the central question of this study?
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What is the main finding and its importance?
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