Endotoxin increases both protein and fluid microvascular permeability in cat skeletal muscle

Abstract

Objective To evaluate effects of lipopolysaccharide (endotoxin) on protein and fluid permeability in a whole organ skeletal muscle preparation. Design Controlled, prospective laboratory study. Setting University research laboratory. Subjects Eleven adult male cats. Interventions The study was performed on the autoperfused and denervated calf muscles of the cat hindlimb placed in a fluid-filled plethysmograph. The endotoxin-induced change in the osmotic reflection coefficient for albumin was used as a measure of alteration in protein permeability of the microvascular wall, and the simultaneous change in capillary filtration coefficient was used as a measure of alteration in fluid permeability. Endotoxin as a bolus infusion (1 mg/kg iv) was given to six cats, and another five cats given only the vehicle (NaCl) were used as control. Measurements and Main Results Arterial blood flow, arterial and venous blood pressures, total vascular resistance, and tissue volume changes were measured continuously. The ratio between the osmotic reflection coefficients for albumin on two occasions (before and about 1.5 hr after endotoxin infusion) was calculated from the Starling fluid equilibrium equation. This was performed by measurement of the maximum absorption rate from an isovolumetric state by an intravenous bolus infusion of 20% human albumin (0.6 g/kg) and the capillary filtration coefficient. Albumin concentrations were measured before and after the albumin infusion to correct for effects of difference in plasma volume on the induced increase in colloid osmotic pressure. We found that the osmotic reflection coefficient for albumin was reduced by 30% (p < .05), and the capillary filtration coefficient was increased by 31% (p < .05) by endotoxin. No changes were seen in the vehicle experiments. Conclusion Endotoxin causes a significant increase in both protein and fluid microvascular wall permeability. These effects may explain the marked leakage of plasma to the interstitium that is often seen in critically ill patients with sepsis and systemic inflammatory response syndrome.