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Capillary permeability to interstitial microinjections of macromolecules and influence of capillary hydrostatic pressure on endothelial ultrastructure.

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.

Animals

Quantitative high-pressure liquid chromatographic procedure for the determination of plasma and tissue levels of 2,4-diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine (metoprine) and its application to the measurement of brain capillary permeability coefficients.

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.

Animals

[Significance of the ability of E. coli to alter capillary permeability for the reproduction of pyelonephritis in mice].

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.

Animals

Effects of glucocorticoids on ventricular performance and capillary permeability during hemorrhagic shock.

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.

Animals

Multiple pathways of capillary permeability.

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.

Animals