The in vivo pH of the extravascular space of the lung

Effros, Richard M.; Chinard, Francis P.

doi:10.1172/jci106164

Cited by 75 publications

(54 citation statements)

References 20 publications

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“…In a healthy human being pH e values come to about pH 7.1 in liver, less than pH 6.9 in active muscle, and only pH 6.7 in the pulmonary extracellular space (67). The in vitro experiments of the present study show that regarding cell motility ( Fig.…”

Section: The Ecm Composition Arranges Motility and Invasionsupporting

confidence: 45%

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Vahle

Domikowsky

Schwöppe

et al. 2013

International Journal of Oncology

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Abstract. The activity of the Na + /H + exchanger NHE1 is required for human melanoma cell adhesion and migration. The goal of the present study was to suppress mouse melanoma (B16V) cell invasion in vivo by inhibiting NHE1. Intravital observations in mobilized left liver lobes of laparotomized male Sprague-Dawley rats disclosed that five minutes after intra-arterial administration of the B16V cell suspension, cells adhered to the endothelia of liver sinusoidal capillaries and started to migrate into the surrounding liver tissue. In the presence of the NHE1-specific inhibitor cariporide, migration/invasion was reduced by about 50% while adhesion was not lowered. Time-lapse video microscopy and adhesion/invasion assays revealed that in vitro, blockade of NHE1 by cariporide i) significantly decreased the migratory speed of the cells and ii) completely inhibited the invasive behavior of both an artificial, basement membrane-like and a dermis-like matrix. Cells were more motile on the basement membrane and more invasive on the dermis-like matrix. Small-animal PET (positron-emission tomography) analyses of B16V metastasis in female C57BL/6 mice showed that, although NHE1 inhibition hardly affected the percentage of animals developing metastases or relapses, metastases seem to get directed to the lungs in cariporide-treated animals while animals feeding on the standard diet show metastases spread all over the body. We conclude that i) B16V cells prefer to invade a dermis-like rather than a basement membranelike matrix; ii) the extracellular matrix (ECM) composition strongly impacts on NHE1-dependent in vitro cell motility and invasion; and iii) the lungs are metastasis-prone and impair the efficiency of cariporide due to their ECM composition and the pulmonary interstitial (extravascular) pH.

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Section: The Ecm Composition Arranges Motility and Invasionsupporting

confidence: 45%

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Vahle

Domikowsky

Schwöppe

et al. 2013

International Journal of Oncology

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“…This effect of increasing the relative pH of the extravascular space has been observed in indicator dilution studies of the lungs and myocardium (16,18,19). Since no significant changes in mean extravascular pH were detected in this preparation with transient studies using the pH indicator, ["4C]DMO, this hypothesis seems unlikely.…”

Section: Resultssupporting

confidence: 61%

Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

Effros¹,

Nioka²

1983

J. Clin. Invest.

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A B ST R A CT The transit of '4C02 and H'4CO3 through the renal vasculature was studied in rabbit kidneys perfused without erythrocytes and in an in vivo preparation in which erythrocytes were present. In the absence of erythrocytes, the transit of 14CO2 from the renal artery to renal vein was much more rapid than that of H'4CO3. This suggests that (a) there is insufficient carbonic anhydrase (c.a.) in the vasculature between the renal artery and the exchange vessels of the kidney to ensure equilibration between CO2 and HCO3 and (b) CO2 can diffuse directly between arterial and venous vessels in the kidney. Following infusions of carbonic anhydrase, the renal venous outflow patterns of '4CO2 and H'4CO3 became the same in the perfused kidneys. Although the initial recovery of 14CO2 remained greater than that of H'4CO3 after infusions of acetazolamide (a c.a. inhibitor), arteriovenous diffusion of "4CO2 was diminished by this agent. This is attributed to inhibition of renal tubular c.a.

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“…The fractions of the injected reference tracer, h R (t), and test tracer, h(t), appearing in the venous outflow per second, were calculated by using the equation (8) In this relationship, h(t) or h R (t) is the fraction of the injected dose of the test or reference tracer per second appearing in the outflow from the femoral vein, F v , in milliliters per second; I is the total injected dose expressed as counts per minute; and C(t) is the concentration of tracer in the femoral venous blood in counts per minute sat time t. If the concentration of albumin (the reference tracer) is zero in the femoral vein at three minutes, it can be assumed that all of the albumin is out of the bone and that the area under the curve for the reference tracer is unity. Hence (9) The instantaneous extraction E(t) can then be calculated from the formula (10) The maximum instantaneous extraction, E max , was taken to be the best indicator of unidirectional transcapillary extraction before back-diffusion became appreciable 3 .…”

Section: Extraction Of Mineralmentioning

confidence: 99%

Extraction of minerals after experimental fractures of the tibia in dogs.

Hughes

Lemon

Davies

et al. 1979

The Journal of Bone & Joint Surgery

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In a study of a standardized fracture of the tibia in dogs, we examined the relationship between extraction of strontium-85, as measured by a multiple indicator-dilution technique, and blood flow, as determined by an iodoantipyrine-washout technique. Although the blood flow at the fracture site increased from a control value of 1.5 milliliters per 100 grams of bone per minute to a value of 6.65 milliliters per 100 grams of bone per minute at two weeks, the maximum instantaneous extraction of 85 Sr by the fractured tibiae did not change from a value of about 0.77 of the amount injected. These results suggest that the increase in blood flow is accomplished by recruitment of capillaries, that the permeabilities of the capillary beds in the fractured tibia and in the normal tibia are similar, and that the pattern of flow in the fractured tibia remains non-uniform. The increased capillary surface area available for exchange is suggested as the reason that strontium extraction was unchanged despite the increased flow.Clinical Relevance-This study has shown that calcium is only moderately rapidly exchangeable across the capillary membrane and made available for uptake by osteoblasts and deposition in callus at the fracture site. Because calcium delivery via capillary is essential, and because capillary surface area is ordinarily increased in the region of a healing fracture, we can now see clearly that clinical treatment, in particular manipulative intervention, should be carried out in a fashion that minimizes damage to the capillary bed. The exchange processes described in this study are the same as those involved in the deposition of agents used for bone-scanning, and thus this information provides a basis for the timing of scanning studies and for their interpretation.The use of tracer kinetics provides an important technique for the study of the metabolic activity of tissues. Tracers that concentrate in bone, such as the isotopes 85 Sr and 47 Ca, have been helpful in examining exchange between circulating blood and bone. The quantity of tracer that enters bone must be related to the blood flow -that is, to the amount of tracer delivered to the bone -and to the diffusion of tracer through the capillary wall of the capillary tube. If bone is like other tissues, the flux of ions and solutes across the capillary wall is related to the flow of the fluid carrying the ions and solutes, to the extraction of ions in the tissue, to the permeability of the capillary wall, and to the surface area of the capillaries.The quantity of tracer that enters bone can be expressed most simply as deposition for a given period of time. For example, if the period is ten minutes, deposition can be expressed by the formula: Dividing deposition by the time of the experiment, ten minutes, gives clearance, which has the units milliliters per gram of bone per minute, the same units as those for blood flow in bone. However, clearance may also be viewed as the minimum volume of blood entering an organ per unit of time which is capable ...

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The in vivo pH of the extravascular space of the lung

Cited by 75 publications

References 20 publications

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Deficiency of carbonic anhydrase in the vasculature of rabbit kidneys.

Extraction of minerals after experimental fractures of the tibia in dogs.

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