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The function of the mural components involved in vascular exchange (pinocytotic vesicles, fenestrations, intercellular junctions, and the basal lamina) was assessed by intravascular injection of tracers (carbon, carbon plus histamine, ferritin, hemoglobin, and myoglobin) on separate gestational days in fetal and neonatal rat intestinal capillaries. The continuous capillaries present through day 17 of gestation were impermeable, even at junctions, to all the tracers within the maximum circulation time studied (3 minutes). Most of the luminal pinocytotic vesicles were labeled within 3 minutes with myoglobin (3.3-nm diameter) or hemoglobin (5.5-nm diameter), while only occasional vesicles contained ferritin (11-nm diameter) and none contained carbon (25-50nm diameter). Even though luminal pinocytotic vesicles contained the smaller tracers, no vesicular transport and discharge were ever seen. The fenestrated vessels present from day 18 of gestation allowed a rapid extravasation of ferritin and hemoglobin via diaphragmed fenestrations. At no time period did extravasation of carbon take place, nor did the carbon plus histamine solution induce vascular leakage. Once a tracer gained access to the extravascular space, the developing basal lamina did not seem to retard its movement.
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Since various macromolecules have experimentally been demonstrated to be taken up by the motor end-plates and subsequently transported through retrograde axoplasmic flow, noxious substances may gain entrance to the lower motorneurons through the same route. Consequently, the function of the capillary barrier in skeletal muscle is of interest in diseases of the lower motorneurons. The transcapillary escape of 125I-albumin was determined in six ALS patients. The values fell within the range earlier reported for normals.
This brief paper reviewed some of the most currently used mathematical models in the field of transcapillary exchange. Mathematical formalism was reduced to its simplest expression and a special emphasis was given to the principles and simplifying hypotheses of each kind of model. We described the simplified formulation of capillary-tissue exchange used for the multiple indicator methods and its generalization using the equations derived from thermodynamics. "Black box" models taking into account the complexity of microcirculatory hemodynamics were also presented. We stressed the importance of interactions between adjacent portions of tissue and the potential influence of tissue-lymphatic exchange in the transcapillary exchange phenomenon.
OBJECTIVE: To investigate the correlation between microalbuminuria and extravascular lung water in patients in septic shock who require mechanical ventilation for severe respiratory failure. DESIGN AND SETTING: Prospective, observational, clinical study in the 20-bed intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 25 consecutive patients in septic shock and also in severe respiratory failure requiring mechanical ventilation. INTERVENTIONS: Hemodynamic parameters and extravascular lung water were determined by single arterial thermodilution. Together with each hemodynamic measurement the PaO(2)/FIO(2) ratio and urinary microalbumin to creatinine ratio (M:Cr) was measured. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were also determined daily. MEASUREMENTS AND RESULTS: The EVLW index was significantly higher than normal throughout the study. Microalbuminuria was in the normal range on entry and remained so for the rest of the study period. Serum PCT and CRP levels were significantly higher than normal at every assessment points. No significant correlation was found between M:Cr and either EVLW or PaO(2)/FIO(2). CONCLUSIONS: In this study patients in septic shock with significantly elevated EVLW had normal urinary M:Cr, and there was no correlation between M:Cr and EWLV, and PaO(2)/FIO(2). Therefore based on the current results routine measurements of microalbuminuria to determine endothelial permeability cannot be recommended in critically ill patients.
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The review provides an update and overview of the role of exchange microvessels in the transfer of materials between circulating blood and metabolizing tissues. Following a presentation of the basic mechanisms governing transvascular movement of water and solutes, both active and passive modulation of vascular permeability are discussed. Some of the issues under current study are highlighted and a few of the questions awaiting answers are raised.
OBJECTIVE: We tested the hypothesis that there is significant solute loss to the superfusate during microvessel solute permeability measurement in frog mesentery which leads to underestimation of permeability coefficient. This is the first application of laser-scanning confocal microscopy to measure microvessel permeability. METHODS: Microvessel permeability to sodium fluorescein (0.5 mg/ml, MW 376) was measured in the presence of bovine serum albumin (10 mg/ml) in Ringer's solution. Every 11-12s an optical section transverse to the vessel axis (x-z section) was collected. The images were corrected for fluorescence attenuation in the z direction and nonuniformity of light collection (shading) in the x direction by comparison to a fluorescent standard. Extravascular fluorescence, which increased linearly with time, and the step increase in fluorescence intensity of the vessel lumen were used to calculate an apparent permeability. Measurements were made first with the tissue superfused with Ringer and second after changing the superfusate to mineral oil in order to retain solute potentially lost to Ringer superfusate. RESULTS: The permeability to fluorescein measured with Ringer superfusate (5.0 +/- SD 2.6 x 10(-5) cm/s; n = 3) was not different from that measured with mineral oil covering the upper mesothelial surface (4.5 +/- 1.9). CONCLUSIONS: Therefore, the loss of sodium fluorescein through the upper mesothelium does not significantly alter permeability under these conditions. These techniques enable detailed analysis of solute concentration gradients surrounding microvessels.
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By using a quantitative Evans blue technique, vascular permeability of Walker carcinosarcomas implanted in the liver was compared with that of the host liver tissue. Rats were sacrificed at intervals from one minute to 96 hours after the intravenous injection of the dye. Permeability activity curves were significantly different for tumors and normal liver. Permeability activity was lower in the tumor at one and five minutes, approximately the same in the tumor and liver from 15 minutes to one hour but, from two hours to 48 hours, the permeability activity was significantly higher in the tumor. The peak tumor-liver permeability activity ratio of 1.87 occurred at six hours, and the highest tumor permeability activity values were seen at 18 hours. Liver permeability activity, in contrast, increased gradually after dye injection, reading peak levels at 24 to 72 hours. At 96 hours, both tumor and liver permeability activity were lower and equal. The differences in permeability activity may be explainable on the basis of structural differences in normal and tumor vessels or may be due to chemical substances released as a result of the presence of the tumor. The differences in permeability activity of tumors and normal tissues may be an important factor in determining the effectiveness of diagnostic and therapeutic techniques.
In an earlier study, plasma was observed to counteract the permeability-increasing effects of blood-free perfusion when papaverine was present in the perfusate. To determine if this plasma effect was still present in the absence of papaverine, cat hindlimbs were perfused with a blood-free albumin-electrolyte solution, and capillary filtration coefficient (CFC) was measured. These data were compared with CFC values obtained when blood, plasma, or isoproterenol were present in the albumin perfusate. In separate groups of animals, CFC was observed to be 0.017 +/- 0.006 (SD, n = 26) ml X min-1 X mmHg-1 X 100 g muscle-1 during blood-free albumin perfusion, 0.012 +/- 0.002 (n = 24) when blood was present, 0.014 +/- 0.003 when isoproterenol was present, and 0.010 +/- 0.002 (n = 33) when both blood and isoproterenol were present. In a separate study, it was observed that 1) isoproterenol could reduce CFC by 11% when added to blood-free perfusate, 2) plasma had a similar but smaller and more variable effect than isoproterenol, 3) plasma had no consistent effect on CFC when added to a blood-free albumin perfusate containing isoproterenol, and 4) blood could reduce CFC significantly (P less than 0.005), from 0.014 +/- 0.003 to 0.0094 +/- 0.002 (n = 7), when added to a blood-free albumin perfusate containing isoproterenol. It was concluded that, in the absence of papaverine, the principal CFC-reducing effect of blood lay in the cell fraction and that isoproterenol had a small CFC-reducing effect under blood-free conditions. This result contrasts with the plasma effect reported earlier.
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