Transvascular flux and tissue accrual of Evans blue: effects of endotoxin and histamine.

We investigated the relationship between the pharmacokinetics of exogenous molecules and transcapillary flux by studying the intravascular and tissue content and the histologic distribution of Evans blue in guinea pigs. Pharmacokinetic analysis demonstrated that 87% of the decline in intravascular Evans blue during the first 3 hours after administration was a result of transvascular flux to tissue compartments. Rapidly and slowly equilibrating compartments were identified. Greater than 90% of the clearances in lung and heart were rapid compartment clearances. Histologically, the distribution of Evans blue in these tissues was predominantly extracellular and similar to the distribution of fluorescein-labeled dextran. By contrast, the accumulation in kidney and liver was kinetically similar to characteristics of the slowly equilibrating compartment. This corresponded histologically to the predominant intracellular uptake of Evans blue in these tissues. Generalized increases in capillary permeability were produced by endotoxin or histamine infusion. Both treatments were associated with a more rapid initial decline in intravascular content of Evans blue than was found in control animals. Although the histologic distribution of Evans blue in tissues was not altered, endotoxin was associated with a more rapid appearance of Evans blue in the lung and heart than was seen in controls. We conclude that the initial decline in intravascular content of Evans blue corresponds to the intercompartmental clearance and to transcapillary macromolecular flux. The initial decline in serum concentrations may therefore be useful in studying disorders of generalized capillary permeability. Furthermore, the initial accrual of Evans blue in the lung and heart may be used as a marker of transcapillary macromolecular flux in those tissues.

[A modified dye dilution method to estimate leakage during regional isolated perfusion of the extremity (author's transl)]. / Eine modifizierte Farbstoffverdünnungsmethode zur Uberprüfung der Kreislaufisolierung der Extremität während regionaler perfusion.

In experiments on dogs (n=13) we tested a procedure for estimating leakage during regional perfusion of the extremity by means of a dye dilution method. After systematic application of 0.5% Evans blue solution (0.1 ml/kg b.w.) we measured the dye concentration in plasma by means of a spectral photometer. The plasma volume (5.5 ml/100 gb.w.) and the disappearance rate of the dye (10%/h) were calculated. In a second procedure the supplying artery and vein of the extremity were proximally clamped and distally connected to an extracorporeal circulation unit consisting of oxygenator, pump, and heat exchanger, and the isolation of the extremity was tested. By simulated of leakage it was possible to detect a little amount of shunt of about 1% escaping from isolated region into the systemic circulation. There were no hints to toxicity when the same dye concentration. There were no hints to toxicity when the same dye concentration was applied. The standardized method was using during 132 cytostatic hyperthermic perfusion in man. In 20 patients we determined shunts of less than 5%, in 104 patients shunts between 5 and 10%, and in eight patients shunts of 10-20% of the extracorporeal circulation. The benefits of the described method are simplicity to carry out and missing of toxicity or radiation.