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

Sepsis is characterized by increased microvascular permeability and regiona l variations in capillary perfusion, which may be modulated by nitric oxide (NO) and reversed by fluid resuscitation (FR). The effects of saline FR an d NO synthase blockade [by N-G-nitro-L-arginine methyl ester (L-NAME)] on m icrovascular albumin transport and perfused capillary density were assessed in anaesthetized Wistar rats with acute normodynamic endotoxaemia. Separat e dual-isotope techniques were employed to measure the permeability index ( PIA) and the permeabilityxsurface area product index (PIB), which provide d ifferent and complementary information regarding blood-tissue albumin excha nge. PIA represents the tissue/blood distribution volume ratio of albumin. PIB is a composite measure of endothelial permeability and the vascular sur face area available for album in exchange, and therefore takes into account the effect of altered blood volume. Capillary density was quantified by fl uorescence microscopy following circulation of Evans Blue-labelled albumin. Compared with controls, PIA was reduced significantly in lipopolysaccharid e (LPS)-treated animals in skeletal muscle and skin, probably due to blood volume redistribution rather than to changes in permeability. PIB was incre ased significantly in LPS-treated animals in the kidney, mesentery, skeleta l muscle, skin and lung, and in the small bowel following FR. FR also impro ved the LPS-induced metabolic base deficit, but did not alter capillary den sity. L-NAME significantly attenuated the LPS-induced rise in PIB in the lu ng. In conclusion, acute endotoxaemia induces tissue-dependent variations i n microvascular albumin exchange. FR improves acid-base disturbance in endo toxaemia, through mechanisms Other than microvascular recruitment. NO appea rs to increase microvascular permeability in endotoxaemia, an effect that m ay be attenuated by L-NAME, particularly in the lung.