Turnover of hyaluronan in the rabbit pleural space

Allen, Steve; Fraser, Russell; Laurent, Ulla B.G.; Reed, Rolf K.; Laurent, Torvard C.

doi:10.1152/jappl.1992.73.4.1457

Cited by 15 publications

(10 citation statements)

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“…Pleural glucose and lactic dehydrogenase concentrations are similar, or slightly smaller than in serum (Sahn & Light 1989); in inflammation, their increase provides, together with a low pH, the most important clinical indicator to distinguish between transudative or exudative pleural disease (Sahn & Light 1989, Joseph et al 2001. Normal pleural fluid HA content is~0.7 lg mL À1 (Allen et al 1992); however, it dramatically increases in malignant pleural effusion (Thylen et al 2001), providing a significant prognostic value for malignant mesothelioma.…”

Section: Pleural Fluid Compositionmentioning

confidence: 99%

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Pleural function and lymphatics

Negrini

Moriondo

2012

Acta Physiologica

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The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies.

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Section: Pleural Fluid Compositionmentioning

confidence: 99%

“…Normal pleural fluid HA content is ~0.7 μg mL −1 (Allen et al . ); however, it dramatically increases in malignant pleural effusion (Thylen et al . ), providing a significant prognostic value for malignant mesothelioma.…”

Section: Pleural Fluid Origin Volume and Compositionmentioning

confidence: 99%

Pleural function and lymphatics

Negrini

Moriondo

2012

Acta Physiologica

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“…Based on the minute quantities of pleural liquid hyaluronan detected in normal control rabbits, Allen et al [5] concluded that the pleural liquid hyaluronan would have a negligible effect on pleural liquid viscosity and thus would not function as an effective hydrodynamic lubricant (whose properties depend on pleural liquid viscous forces). Moreover, the increase in hyaluronan concentration caused by the increased ventilation in rabbits breathing 3% CO 2 is likely to cause only a slight increase in pleural liquid viscosity.…”

Section: Factors Affecting Pleural Liquid Hyaluronan Concentrationmentioning

confidence: 99%

Effects of Ventilation on Hyaluronan and Protein Concentration in Pleural Liquid of Anesthetized and Conscious Rabbits

Wang

Lai-Fook

1998

Lung

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The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.

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“…The liver specifically eliminates endogenous HA, therefore rapid and continuous elimination of HA from the circulation by the liver was expected. 13,15,19 The kidneys had lower levels than the liver but more than the heart, spleen, and bladder, suggesting that urinary excretion may be another potential route for eliminating the small amounts of HA absorbed systemically from the lung. 12–14 HA content in the bladder tissue was low at all time points.…”

Section: Discussionmentioning

confidence: 99%

“…7–13 Thus, HA serves as an interesting polymer to carry drugs. Absorption of HA after subcutaneous, 14–18 intraperitoneal, 19 oral, 20,21 and intravenous injection 22–24 has been reported, but the fate of HA after pulmonary administration is not well understood. Recent work suggesting that HA may be useful for inhaled drug delivery motivates a better understanding of HA fate after pulmonary administration.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation

et al. 2016

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Hyaluronic acid (HA) has emerged as a versatile polymer for drug delivery. Multiple commercial products utilize HA, it can be obtained in a variety of molecular weights, and it offers chemical handles for cross-linkers, drugs, or imaging agents. Previous studies have investigated multiple administration routes, but the absorption, biodistribution, and pharmacokinetics of HA after delivery to the lung is relatively unknown. Here, pharmacokinetic parameters were investigated by delivering different molecular weights of HA (between 7 and 741 kDa) to the lungs of mice. HA was labeled with either a near-infrared dye or with iodine-125 conjugated to HA using a tyrosine linker. In initial studies, dye-labeled HA was instilled into the lungs and fluorescent images of organs were collected at 1, 8, and 24 h post administration. Data suggested longer lung persistence of higher molecular weight HA, but signal diminished for all molecular weights at 8 h. To better quantitate pharmacokinetic parameters, different molecular weights of iodine-125 labeled HA were instilled and organ radioactivity was determined after 1, 2, 4, 6, and 8 h. The data showed that, after instillation, the lungs contained the highest levels of HA, as expected, followed by the gastrointestinal tract. Smaller molecular weights of HA showed more rapid systemic distribution, while 67 and 215 kDa HA showed longer persistence in the lungs. Lung exposure appeared to be optimum in this size range due to the rapid absorption of <67 kDa HA and the poor lung penetration and mucociliary clearance of viscous solutions of HA > 215 kDa. The versatility of HA molecular weight and conjugation chemistries may, therefore, provide new opportunities to extend pulmonary drug exposure and potentially facilitate access to lymph nodes draining the pulmonary bed.

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Turnover of hyaluronan in the rabbit pleural space

Cited by 15 publications

References 0 publications

Pleural function and lymphatics

Pleural function and lymphatics

Effects of Ventilation on Hyaluronan and Protein Concentration in Pleural Liquid of Anesthetized and Conscious Rabbits

Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation

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