Regional transcapillary albumin exchange in rodent endotoxaemia: effects of fluid resuscitation and inhibition of nitric oxide synthase

Abstract

Sepsis is characterized by increased microvascular permeability and regional variations in capillary perfusion, which may be modulated by nitric oxide (NO) and reversed by fluid resuscitation (FR). The effects of saline FR and NO synthase blockade [by N(G)-nitro-L-arginine methyl ester (L-NAME)] on microvascular albumin transport and perfused capillary density were assessed in anaesthetized Wistar rats with acute normodynamic endotoxaemia. Separate dual-isotope techniques were employed to measure the permeability index (PI(A)) and the permeabilityxsurface area product index (PI(B)), which provide different and complementary information regarding blood-tissue albumin exchange. PI(A) represents the tissue/blood distribution volume ratio of albumin. PI(B) is a composite measure of endothelial permeability and the vascular surface area available for albumin exchange, and therefore takes into account the effect of altered blood volume. Capillary density was quantified by fluorescence microscopy following circulation of Evans Blue-labelled albumin. Compared with controls, PI(A) was reduced significantly in lipopolysaccharide (LPS)-treated animals in skeletal muscle and skin, probably due to blood volume redistribution rather than to changes in permeability. PI(B) was increased significantly in LPS-treated animals in the kidney, mesentery, skeletal muscle, skin and lung, and in the small bowel following FR. FR also improved the LPS-induced metabolic base deficit, but did not alter capillary density. L-NAME significantly attenuated the LPS-induced rise in PI(B) in the lung. In conclusion, acute endotoxaemia induces tissue-dependent variations in microvascular albumin exchange. FR improves acid-base disturbance in endotoxaemia, through mechanisms other than microvascular recruitment. NO appears to increase microvascular permeability in endotoxaemia, an effect that may be attenuated by L-NAME, particularly in the lung.

Marked increase in vascular endothelial growth factor concentrations during Escherichia coli endotoxin‐induced acute inflammation in humans

“…Other mechanisms causing vascular leakage during inflammation have also been described. For example, nitric oxide formation also seems to influence vascular permeability [29]. In vitro experiments suggest that VEGF release from macrophages is regulated by nitric oxide [30].…”

Physicochemical, tissue distribution, and vasodilation characteristics of nitrosated serum albumin: delivery of nitric oxide in vivo

“…The effects of NO‐BSA on vascular permeability of macromolecules were evaluated as reported previously 25 with some slight modification. Briefly, 111 In‐BSA was injected into the tail vein of mice at a dose of 1 mg/kg.…”