Article

Reactive oxygen metabolites inhibit spontaneous lymphatic contraction

Microcirculation Research Institute, College of Medicine, Texas A&M University, College Station 77843-1114.
The American journal of physiology (Impact Factor: 3.28). 07/1991; 260(6 Pt 2):H1935-43.
Source: PubMed

ABSTRACT

The effects of oxygen-derived free radicals on the contractile activity of the mesenteric collecting lymphatics were evaluated in the anesthetized rat. Lymphatic contractions were monitored before, during and after the application of oxyradicals. Contraction frequency (F), stroke volume (SV), ejection fraction (EF), contraction propagation (PC), and lymph pump flow (LPF) were determined from the lymphatic diameter tracings. Oxyradicals were generated using hypoxanthine and xanthine oxidase. Exposure to oxyradicals inhibited the lymphatic pumping mechanism: 1) F fell from 15.5 +/- 0.8 to 0.8 +/- 0.7 beats/min; 2) EF went from 0.44 +/- 0.02 to 0.08 +/- 0.04; 3) PC dropped from 92 +/- 2 to 56 +/- 8%; and 4) LPF fell precipitously from 41.0 +/- 5.2 to 0.7 +/- 0.4 nl/min. The effects of the oxyradicals were attenuated by superoxide dismutase, implicating superoxide anion as one of the predominant causative agents. We conclude that oxyradicals significantly inhibit the lymph pump and that this inhibition could be a factor contributing to the formation of interstitial edema during inflammation.

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Available from: David Carl Zawieja
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    • "To measure the diameter of the lymphatic vessel under investigation, the vessel walls were tracked throughout the recording using a customdesigned automated, correlation-based algorithm similar to that described in details in (Dixon et al., 2006; Akl et al., 2011; Davis et al., 2011). We used the continuous diameter tracings to define systole and diastole in reference to the lymphatic contractile cycle (Zawieja et al., 1991; Gashev et al., 2004). The end-diastolic and end-systolic points in the diameter tracings were recorded. "
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    ABSTRACT: The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Full-text · Article · Dec 2014 · Aging Cell
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    • "We used cardiac pump analogies to define systolic and diastolic lymphatic diameters in reference to the lymphatic contractile cycle (Granger et al. 1977; Benoit et al. 1989; Zawieja et al. 1991; Gashev et al. 2004) and the end-diastolic and end-systolic points in the diameter tracings were recorded for each 5 min interval for each set of pressures and imposed flow with or without drugs used. From the lymphatic end-diastolic and end-systolic diameters (EDD and ESD), the following lymph pump parameters were calculated: lymphatic tone index (the difference between the passive lymphatic diameter in calcium-free APSS and EDD, expressed as a percentage of the passive lymphatic diameter in calcium-free APSS), contraction amplitude (the difference between EDD and ESD), contraction frequency, ejection fraction [EF, the fraction of end-diastolic volume ejected during the single lymphatic contraction, calculated using formula EF = "
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    • "basal lymphatic parameters and allows for a more sensitive investigation of the controlled parameters by preventing the observed changes in lymphatic function from being superimposed on normal random variations in vessel sizes between normal animals. Normalizations of a similar nature are commonly used in lymphatic studies (Zawieja et al. 1991; von der Weid et al. 1996; von der Weid & Van Helden, 1996; Hollywood et al. 1997; Mizuno et al. 1998; von der Weid, 1998; Koller et al. 1999; Mizuno et al. 1999; Shirasawa et al. 2000; von der Weid et al. 2001; Gashev, 2002; Gashev et al. 2002, 2004) and other microcirculatory studies (Kuo et al. 1988, 1990a,b; Meininger et al. 1991; Hill & Gould, 1997; Hiramatsu et al. 1998; Guibert & Beech, 1999). "
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    Full-text · Article · Oct 2006 · The Journal of Physiology
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