Vascular permeability factors in the secretion of the guinea pig coagulating gland.
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Barium chromate, Prussian blue, and cobalt-cobalticyanide can be precipitated in vivo in the endothelium of mesenteric vessels by injection of the appropriate anions into the blood stream, and topical application of the precipitating cations to the exposed mesenteries of mice and frogs. Precipitation in the endothelium occurs in the form of a diffuse fine punctate precipitate, and also as continuous lines demarcating endothelial cell outlines. A striking feature is the frequent occurrence of this type of precipitation in a tapering zone downstream from mural thrombi in the veins.
The local Shwartzman reaction was provoked in the skin of the ear, hind leg, and costovertebral angle of the rabbit, as well as in the ventral abdominal skin. Certain adrenergic blocking drugs reduced the incidence of positive reactions when given prior to the provocative dose of bacterial polysaccharide. Epinephrine and other vasoconstrictor drugs administered intradermally into the prepared skin site produced typical hemorrhagic-necrotic lesions when the usual intravenous injection of polysaccharide was omitted. This reaction could be blocked by adrenergic blocking drugs, but appeared to be augmented by heparin or nitrogen mustard. A hypothesis has been developed to help explain the mechanism of the local Shwartzman reaction. Following the preparatory dose, tissue metabolic changes occur which lead to increased lactic acid production and render the area particularly susceptible to anoxia. Following the provocative dose, adrenergic vasoconstriction occurs. It is suggested that this vasoconstriction may be intensified at the prepared site by small residual amounts of the preparatory dose of polysaccharide which might potentiate the action of the epinephrine. The anoxia initiated by the vasoconstriction is prolonged and intensified by the formation of intravascular thrombi around clumps of leucocytes and platelets. This anoxia, superimposed on the local metabolic changes, leads to the characteristic lesion of hemorrhage and necrosis. Thus a combination of factors, all of causal importance and largely due to known pharmacologic properties of bacterial lipopolysaccharide, occur in specific sequence to lead to the classic local Shwartzman reaction.
Experiments giving evidence of active Na and Cl ion fluxes across large canine blood vessel walls (aorta, vena cava) in vitro have been presented. The information has been obtained using ion tracer techniques after Ussing and with diffusion cells of the Hogben type. The available data suggest that the membranes are satisfactorily oxygenated by the bathing solutions saturated with oxygen at atmospheric pressure. Evidence is offered which indicates that active ion transport does occur across the aorta and vena cava in in vitro experiments. Under the conditions of the experiment net Na and Cl flux takes place from intima to adventitia across the aorta, and from adventitia to intima across the vena cava at low measured potential differences. The possible relationships of derangement of active ion transport mechanisms, produced by electric currents and tissue injury potential differences, to intravascular thrombosis are alluded to. It would appear that sodium and chloride fluxes across large blood vessel walls in vitro occur at least in part as the result of metabolic processes and cannot be explained simply on the basis of diffusion across a semipermeable membrane.
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