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The assumption inherent to the single injection residue function method to determine capillary permeability have been made explicit. Furthermore, it is shown that agreement between the deduced wash-out function of the transmitted molecules of the test substances and that of reference molecules does not constitute proof of the validity of the method.
We propose a new test for measuring the "capillary permeability" with labeled albumin, with simpler methods, satisfactory results and good discrimination between normal subjects and pathological patients. In normal subjects, after the removal of the tourniquet, the radioactivity returns to former values (under 10% of this figure). In pathological patients, even after the 3 min following the removal of the tourniquet, there is no return to the former value (the retention of labeled albumin is always over 10%). It is in cyclic oedema that the test provides the most interesting results.
A case of severe hypovolaemic shock related to idiopathic oedema was observed in a 37 year old woman. Large plasma volume expansion (nearly 12 1 over 9 hours) did not change the clinical status. Haemodynamic studies showed low cardiac index (1.1 1/min/m2), decreased left ventricular stroke work index (6.7 gm/m2), and high systemic arterial resistance (52 mmHg/1/min/m2). Dopamine infusion improved the haemodynamic condition which returned to normal 30 hours after the beginning of shock. After recovery, capillary permeability measured by a modification of Landis' method was markedly increased. A study of albumin metabolism showed a normal intravascular pool and a rapid exchange compartment with a twofold increase in slow exchange compartment. Hormonal levels and complement fractions were within normal limits. Serum protein immuno-electrophoresis showed an abnormal IgG. These results clearly demonstrate that hypovolaemia is related to increased capillary permeability and leakage of albumin out of the vascular space. When large infusions fail, inotropic agents, especially Dopamine, should be used in such cases.
Measurements of filtration coefficients (Lp) and osmotic reflexion coefficients (sigma) of single capillaries in the frog mesentery suggest that fluid flows through the walls of these vessels in two types of channel. One channel type (representing about 10% of Lp) appears to be exclusively available for water whereas the other channels appear available for both water and hydrophilic solutes though they severely restrict the passage of albumin (sigma = 0.81). The effects of proteins in the perfusate upon Lp and studies on the passage of ferritin into the surface vesicles of the endothelial cells, suggest that an important component of capillary permeability may reside in an endocapillary layer.
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Electron microscopic and histochemical studies of capillary permeability in the central nervous system were carried out in experiments on albino rats during burn shock. Exogenous peroxidase marker was used for this purpose. During burn shock capillary wall in the central nervous system proved to be permeable for the substance of 40 000 mol wt, such as peroxidase.
OBJECTIVE: The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo. METHODS: Free radicals were generated by simultaneous intracoronary infusion of hypoxanthine and xanthine oxidase into normally perfused myocardium, and at reperfusion following five minutes of coronary occlusion, respectively, in 20 anaesthetised open chest dogs. Myocardial capillary extraction for 99mTc-DTPA, plasma flow rate, and the interstitial washout rate constant were measured by the single injection, residue detection method, and the capillary permeability-surface area product (PS) was calculated. The maximum plasma flow during reactive hyperaemia was measured by the local 133Xe washout method. RESULTS: Hypoxanthine and xanthine oxidase infusion into normally perfused myocardium induced a 15% decrease in capillary extraction (p = 0.05), a 24% decrease in PS (p < 0.01), and a 23% decrease in the interstitial washout rate constant (NS) two minutes after the end of the infusion. When hypoxanthine and xanthine oxidase were infused into postischaemic myocardium, 86% of animals developed sustained ventricular arrhythmias, in contrast to none in control experiments (p < 0.05). The maximum plasma flow was 363% of preocclusive values in control experiments v 268% in hypoxanthine + xanthine oxidase experiments (p < 0.05). CONCLUSIONS: In normally perfused hearts, intracoronary infusion of hypoxanthine and xanthine oxidase induce a decreased capillary extraction, suggesting a reduced capillary surface area. In postischaemic myocardium these substances cause a decreased vasodilatation in the initial phase of reactive hyperaemia, and induce ventricular arrhythmias.
1. An index of capillary permeability was obtained by measuring the ratio of the clearance rate of 77Br to that of 133Xe in the anterior tibial muscle, after a short period of maximal ischaemic exercise. 2. Seventeen control subjects and thirty-two maturity-onset, non-insulin-treated diabetic subjects, aged 60 years or less, were studied. Short glucose tolerance tests were performed in the diabetic subjects during which blood sugar and serum insulin concentrations were estimated. 3. The 77Br/133Xe clearance ratio was increased in the diabetic subjects compared with the control subjects. In the diabetic subjects, there was an inverse correlation between the insulin at 60 min after glucose and the 77Br/133Xe clearance ratio. There was also a direct correlation between the 77Br/133Xe clearance ratio and the age of the patient in the diabetic group but not in the control group. 4. The results demonstrate that a reduced insulin response to oral glucose is associated with increased capillary permability and may play a role in the development of microangiopathy.
Self-limited noncardiogenic interstitial pulmonary edema probably reflecting altered permeability of the pulmonary capillary membrane is reported in a patient being treated for severe diabetic ketoacidosis. The possible etiology, associated findings, and therapy with continuous positive airway pressure (CPAP) by facemask are discussed.
The transcapillary flux of horseradish peroxidase (HRP, mol. diam. 50--60 A) and ferritin (mol. diam. 110--120 A), microinjected interstitially into the biceps femoris muscle of rats, was analyzed in the electron microscope. From 1 min postinjection HRP was observed to occupy endothelial plasmalemmal vesicles in all positions to be expected if a vesicular transendothelial transport of material occurs in the interstitium-to-lumen direction. Permeation of HRP through the intercellular clefts of the endothelium could not be demonstrated unequivocally. The periendothelial basement membrane appeared to constitute a significant permeability barrier against ferritin. The endothelial ultrastructure in muscle capillaries was analysed morphometrically after artificial perfusions of rat hindquarters at venous outflow pressures of -4 cm H2O and +10 cm H2O. In the "high pressure" material the endothelium was thinner and the frequency of vesicles open towards the interstitium was lower than after perfusion at low outflow pressure. The findings may indicate that net transendothelial transport via vesicles varies with hemodynamics.
Sudden injections of boluses containing both 131I-albumin and 24NaCl were made into the coronary artery inflow of isolated blood-perfused dog hearts. Indicator dilution curves were recorded using gamma emissions from both the intact heart and the coronary sinus outflow, with plasma flows, Fs, ranging from 0.3 to 1.8 ml/g min-1. Three measures of sodium extraction, E, during transcapillary passage were obtained from each site by comparison of the sodium and albumin curves. The most useful estimates of E were "instantaneous extractions" obtained from the later part of the upslope and the peak of the venous dilution curves (coronary sinus) or from the corresponding early phase of washout of the externally monitored curves (intact organ). Extractions were lower at higher flows. Permeability-surface area products, PS, were computed (1) by the formula PS equals -Fsloge(1 - E), (2) by fitting the observed dilution curves with a Krogh capillary-tissue cylinder model, and (3) by the approximating formula PS equals -Fsloge (1 - 1.14E). The two latter approaches provided a correction for back diffusion of tracer from tissue to blood. For sodium, the values of PS averaged 0.88 +/- 0.36 (SD) ml/g min-1, (n equals 52). At high flows, with Fs greater than 1.0 ml/g min-1, the values of PS averaged 1.01 +/- 0.38 ml/g min-1 (N equals 11). Assuming S equals 500 cm2/g and plasma to be 93% water, our findings suggest capillary permeabilities for sodium of about 3.1 times 10(-5) cm/sec.
A high-pressure liquid chromatographic assay for metoprine levels in aqueous media, serum, and tissue extracts has been developed that can measure concentrations of the drug in the 25-100 ng range with accuracy, reproducibility, and ease. The half-time for metoprine disappearance from rat plasma and capillary permeability coefficients for metroprine in rate brain tissue determined with this method are in excellent agreement with values determined for related drugs using labeled compounds.
Measurements of transcapillary exchange of high-molecular dextrans, K+ and THO in the rete mirabile of eel (Anguilla vulgaris L.) have been made under steady-state conditions while the transcapillary pressure was varied and pharmaca added to the perfusates. Raising the transcapillary input pressure increased the exchange of dextrans and K+ but lowered that of THO. Histamine and ouabain had no effect on the transcapillary exchange of the test molecules. The highest dose (100 mug/ml) of serotonin reversibly increased the capillary permeability of D-75 000, K+ and THO while the medium dose (50 mug/ml) only raised the transcapillary exchange of K+ and THO. The lowest dose (10 mug/ml) had no permeability effect. Our main conclusion is that serotonin reversibly increases the area of the intercellular pores by affecting the capillary wall directly.
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Experiments in a number of biological models showed that the cultures of E. coli isolated from the urine of children with pyelonephritis had a varied spectrum of pathogenic properties. Histologically confirmed pyelonephritis induced by intravenous infection in CBA mice, treated with 5% glucose by the method of Montgomerie et al., correlated with the bacterial adhesiveness to the epithelium and the interference with capillary permeability, registered in experiments on the pulmonary model with Evans blue used for control. The criterion for the development of pyelonephritis in mice, which was based, in the opinion of Mintogemerie et al., on the positive results, indicating the presence of the infecting agent in the culture obtained by inoculation with the samples of urine and kidney tissue, was found to be insufficient, as only 28 out of 45 cultures of E. coli isolated from the kidneys coincided with histologically confirmed cases of pyelonephritis.
The effects of glucocorticoids on fluid uptake and myocardial performance was investigated in 14 dogs and two baboons. The animals were placed into stimulated hemorrhagic shock using a servocontrolled pump to maintain arterial pressure at desired levels. Ventricular function curves were generated by stepwise changes in afterload or by venous infusion and the resultant data were grouped by digital computer into similar preload, heart rate, and afterload groupings. Fluid uptake was monitored from the pump reservoir. Methylprednisolone was given intravenously, 30 mg/kg, approximately 3 hr after the postinfusion period. Fluid loss decreased and ventricular performance improved, as measured by maximal dp/dt, (maximal dp/dt)/developed pressure, and time to peak ventricular pressure. The improvements with steroid infusion were relatively small, however, and were not maintained for more than about 3 hr. Heart rate decreased markedly in response to the steroid, despite a general vasodilator response. The glucocorticoids appear to have mild beneficial effects on the myocardium and on capillary permeability in the presence of high circulating levels of catecholamines in the postinfusion phase of hemorrhagic shock.
Hemodynamic data were collected in 42 patients with pulmonary edema (P.E.) due to altered permeability of various causes. Pulmonary artery wedge pressure (PWP) was normal, whatever the time of the study and the severity of the P.E. Pulmonary artery hypertension was present in the cases with severe hypoxemia, but disappeared with hypoxemia correction. In some cases, a hyperkinetic or a hypovolemic syndrome was found, being induced by the cause of P.E. Although within normal limits, PWP was significantly higher at the first hours of P.E. than after the 6th hour. Perfusion of colloid solutes worsened P.E., although increasing PWP by only a few mmHg. Dehydration using diuretics markedly improved the venous admixture, although PWP was previously normal. These data document the production of P.E. in many causes-such as severe sepsis, drowning, fat embolism, barbiturate overdose-by impaired alveolo-capillary permeability, PWP and blood protein content remaining within normal limits. They also demonstrate the noxious effects of overperfusion and the efficiency of dehydration in such pulmonary edemas.
Morphological and physiological studies indicate multiple routes for transport across capillary endothelium. However, the identification of the morphological counterparts of specific transport processes (or the assignment of specific transport roles to morphologically identifiable pathways) has been only partly achieved: the contribution of endothelial cell membranes to transport of water and small, lipid-insoluble molecules needs to be evaluated. The identification of the "small pore" pathway for water and lipid-insoluble molecules with the intercellular junctions still remains questionable. The contributions to total macromolecular transport of junctions, single vesicles (pinocytosis, cytopempsis), chains of vesicles, and fenestrae are not yet known.