Role of bulk fluid flow in protein permeability of the dog lung alveolar membrane

In five anesthetized, closed-thorax dogs, we measured net tracer albumin (RISA) uptake rate from an isosmotic buffer-filled lung lobe for 6 h; 3 h at each of two different alveolar RISA concentrations. We calculated the permeability coefficient assuming a two-compartment (alveolar fluid and plasma) diffusional model. In every dog the permeability coefficient decreased after the alveolar RISA concentration was increased. After freezing the lungs terminally, we found the fluid-filled lobes had extensive free interstitial fluid perivascular cuffs, indicating a third compartment filled by bulk flow. In separate experiments, we filled isolated lung lobes with buffer containing RISA and microsampled free interstitial fluid. The free interstitial fluid RISA concentration averaged 90% of airway concentration. The interstitium appears to fill by bulk flow through low-resistance channels. Tracer protein uptake from a fluid-filled lung lobe involves three fluid compartments. We postulate fluid and protein enter the interstitium by bulk flow along a hydrostatic pressure gradient, and protein then diffuses into plasma from the interstitium.

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Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

Archivos de Neurociencias ◽

10.31157/archneurosciencesmex.v21i2.116 ◽

2016 ◽

Vol 21 (2) ◽

pp. 28-37

Author(s):

Oscar Solís-Salgado ◽

José Luis López-Payares ◽

Mauricio Ayala-González

Keyword(s):

Amyloid Beta ◽

Interstitial Fluid ◽

Amyloid Β ◽

Bulk Flow ◽

Polyethylene Glycols ◽

Brain Interstitial Fluid ◽

El Sistema ◽

Arterial Pulsation ◽

The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

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Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit

AJP Renal Physiology ◽

10.1152/ajprenal.1981.240.4.f329 ◽

1981 ◽

Vol 240 (4) ◽

pp. F329-F336 ◽

Cited By ~ 31

Author(s):

M. W. Bradbury ◽

H. F. Cserr ◽

R. J. Westrop

Keyword(s):

Cerebrospinal Fluid ◽

Caudate Nucleus ◽

Subarachnoid Space ◽

Interstitial Fluid ◽

Bulk Flow ◽

Perivascular Spaces ◽

Csf Analysis ◽

Intraventricular Injections ◽

Intracerebral Microinjection ◽

Do So

Lymph from the jugular lymph trunks of anesthetized rabbits has been continuously collected and radioiodinated albumin (RISA) therein estimated after microinjection of 1 microliter of 131I-albumin into the caudate nucleus, after single intraventricular injections, and during intraventricular infusions. Comparison of lymph at 7 and 25 h after intracerebral microinjection with efflux of radioactivity from whole brain suggests that about 50% of cleared radioactivity goes through lymph. Concentrations, normalized to cerebrospinal fluid (CSF), were much higher in lymph and retropharyngeal nodes after brain injection than after CSF injection or infusion. Also after brain injection, lymph and nodes contained more activity on injected side in contrast to lack of laterality after CSF administration. Calculation suggests that less than 30% of RISA cleared from brain can do so via a pool of well-mixed CSF. Analysis of tissues is compatible with much RISA draining by bulk flow via cerebral perivascular spaces plus passage from subarachnoid space of olfactory lobes into submucous spaces of nose and thus to lymph.

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Secretion and Bulk Flow of Interstitial Fluid

Physiology and Pharmacology of the Blood-Brain Barrier - Handbook of Experimental Pharmacology ◽

10.1007/978-3-642-76894-1_9 ◽

1992 ◽

pp. 245-261 ◽

Cited By ~ 29

Author(s):

H. F. Cserr ◽

C. S. Patlak

Keyword(s):

Interstitial Fluid ◽

Bulk Flow

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High Resolution DCE-MRI Vascular Characterization of Murine Sarcoma and Human Renal Cell Carcinoma for Computational Modeling

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-193179 ◽

2008 ◽

Author(s):

Gregory L. Pishko ◽

Garrett W. Astary ◽

Thomas H. Mareci ◽

Malisa Sarntinoranont

Keyword(s):

Interstitial Fluid ◽

Tumor Tissue ◽

Fluid Motion ◽

Fluid Pressure ◽

Bulk Fluid ◽

Human Renal Cell Carcinoma ◽

Dce Mri ◽

Heterogeneous Tissue ◽

Murine Sarcoma

Non-uniform extravasation from blood vessels, elevated interstitial fluid pressure (IFP), and transport by bulk fluid motion in the extracellular space have all been determined to contribute to the non-uniform tissue distribution of systemically delivered agents in solid tumors. The aforementioned factors can lead to inadequate and uneven uptake in tumor tissue which has been shown to be a major obstacle to macromolecules in clinical cancer therapy [1]. Recently developed computational tumor models have described blood flow either in a single vessel or capillary network with variations in space and time [2]. These studies do not account for heterogeneous tissue transport properties in regions of leakier vessels [3].

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Volume shifts with partial submersion of isolated lung lobes

Journal of Applied Physiology ◽

10.1152/jappl.1979.47.6.1143 ◽

1979 ◽

Vol 47 (6) ◽

pp. 1143-1147 ◽

Cited By ~ 1

Author(s):

G. T. Ford ◽

D. Gillett ◽

N. R. Anthonisen

Keyword(s):

Airway Pressure ◽

Compressive Force ◽

Water Displacement ◽

Lung Lobe ◽

Isolated Lung ◽

Tissue Movement ◽

Volume Shift ◽

Lung Lobes

When an isolated lung lobe is partially submerged, volume moves from the submerged part to the unsubmerged part. We partially submerged isolated dog lobes of known weight and volume, and measured airway pressure and, by water displacement, the volume of the submerged part. The lobe was then air-dried and sectioned at the waterline and each part weighed. Multiplying lobar volume by the fractional weight of the submerged part yielded the volume of the submerged part before immersion, and therefore the volume shift to the unsubmerged part due to immersion. Dividing this volume shift by the immersion-induced change in airway pressure gave the compliance (Cr') of the unsubmerged part. Cr' was compared to Cr, the compliance of the unsubmerged part when it was inflated with air. Cr/Cr' was linearly related to the degree of immersion: as immersion increased Cr/Cr' fell; so when lobes were 80% immersed Cr/Cr' was 0.3--0.5, indicating that compressing the lower part of the lung made the upper easier to expand. This behavior could be explained if with immersion lung units moved from the submerged part to the unsubmerged part and this shift increased with the degree of immersion. We demonstrated that when one part of a lobe was compressed lung units moved away from the compressive force and that this movement could occur without similar movement of the pleural surace. Tissue movement probably accounted at least in part for our results.

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Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology

Neurochemistry International ◽

10.1016/j.neuint.2003.11.006 ◽

2004 ◽

Vol 45 (4) ◽

pp. 545-552 ◽

Cited By ~ 469

Author(s):

N.Joan Abbott

Keyword(s):

Interstitial Fluid ◽

Bulk Flow ◽

Brain Interstitial Fluid

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Effects of atropine on natural deflation flows and P-V curves of the isolated lung lobe

Journal of Applied Physiology ◽

10.1152/jappl.1975.38.1.46 ◽

1975 ◽

Vol 38 (1) ◽

pp. 46-51 ◽

Cited By ~ 3

Author(s):

E. Goldman ◽

R. J. Puy

Keyword(s):

Lung Volume ◽

Static Pressure ◽

Transpulmonary Pressure ◽

Significant Shift ◽

Lung Lobe ◽

Isolated Lung ◽

Before And After ◽

Proportionate Change ◽

Airway Conductance ◽

Lung Lobes

Static pressure-volume (P-V) curves and natural deflation flows (NDF) in isolated dog's lung lobes were obtained before and after atropine. Since elastic pressure was the driving force for the expiratory flow this preparation was devoid of the influence of compressive forces. A significant shift to the left of the P-V curve was observed after atropine. Mean increase in volume in the range from 30 to 2 cmH2O transpulmonary pressure (Ptp) was 0.6 ml/g (about 4% increase in percent of maximal lung volume MLV). NDF at the same Ptp (referred to as airway conductance) were significantly higher after atropine (mean increase 3 ml/s per g, about 0.15 l/s). Increase in lung volume after atropine was interpreted as evidence of relaxation of residual bronchomotor tone which in turn, by increasing airway diameters, may produce higher flows. When NDF were plotted against volume, differences between control and atropine were reduced. This was attributed to the observed leftward displacement of the P-V curve. The linear relationship found between NDF and volume in the range 2–8 cmH2O of Ptp (about 35–75% MLV) suggests a proportionate change in airway conductance with lung size. This could indicate that the lobes behaved homogeneously during passive deflation. This pattern was not modified by atropine.

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Adverse effects of prostacyclin used to perfuse isolated lung lobes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.242.5.h745 ◽

1982 ◽

Vol 242 (5) ◽

pp. H745-H750 ◽

Cited By ~ 1

Author(s):

M. M. Krausz ◽

T. Utsunomiya ◽

L. L. Levine ◽

B. Dunham ◽

D. Shepro ◽

...

Keyword(s):

Hydrolysis Product ◽

Weight Ratio ◽

Dry Weight ◽

Antiplatelet Antibody ◽

Lung Lobe ◽

Isolated Lung ◽

Stable Product ◽

Wet Weight ◽

Pulmonary Arterial ◽

Foreign Surface

To test the hypothesis that preservation of circulating platelets would prolong the function of an isolated perfused canine lung lobe, prostacyclin (PGI2) was added to the perfusate. Platelet count in heparinized controls (n = 7) fell to 44,500 platelets/mm3, lower than 136,000 platelets/mm3 seen with 1 microgram/min PGI2 (n = 7, P less than 0.005). Surprisingly, with PGI2, thromboxane B2 (TXB2) the stable product of thromboxane A2 (TXA2), rose from 0.07 to 0.25 ng/ml, a level higher than controls (P less than 0.005). PGI2, in comparison to controls, also led to higher pulmonary arterial pressure, an increase in lobe weight, an increase in wet weight-dry weight ratio, an increase in physiological shunt, and a decrease in compliance (P less than 0.005). Further, with PGI2 there was hemorrhagic edema. Infusion of the PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (n = 2) led to results similar to controls. Adverse PGI2 effects were eliminated by pretreatment with ibuprofen (12.5 mg/kg, n = 5) or an antiplatelet antibody (n = 6). Infusion of PGI2 into a lobar pulmonary artery of an intact animal was without effect on the lung (n = 2). These results show that platelets exposed to a foreign surface will aggregate and be lost from the circulation. PGI2 prevents platelet loss but not the synthesis of TXA2. This vasoconstrictor is likely to be the cause of pulmonary hypertension and hemorrhagic pulmonary edema.

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