Effect of endotoxin on the integrity of the peripheral (soft tissue) microcirculation.
Peripheral edema, hypoproteinemia, and increased fluid requirements are characteristically seen with sepsis. Our purpose was to determine whether the soft tissue edema is caused by a direct vascular injury from sepsis or is secondary to hypoproteinemia. We determined the effect of endotoxin on peripheral (soft tissue) microvascular integrity using lymph flow (QL) and lymph/plasma (L/P) protein ratio to reflect fluid flux and increased permeability. Response was compared with that seen in the lung. Fourteen unanesthetized sheep were given intravenous E. coli endotoxin 2 micrograms/kg. Vascular pressures and cardiac output (CO) were maintained constant with the necessary fluid infusion. Lung QL increased two- to fourfold in all animals with lymph being protein-rich, indicating increased permeability. Peripheral QL increased transiently in response to an initial increase in vascular pressure returning rapidly to baseline except in those animals (N = 5) demonstrating hypoproteinemia where QL remained increased by 50 to 75%. The increased QL was totally explained by the degree of protein depletion, with no evidence of increased permeability. To assure an adequate endotoxin exposure to the peripheral microvessels, endotoxin (2 micrograms/kg) was also directly injected into the tissue drained by the soft tissue lymphatic. We noted a characteristic endotoxin pulmonary hypertension phase but, again, no increase in peripheral microvascular permeability was found. We conclude that endotoxemia does not alter peripheral microvascular permeability if tissue perfusion is maintained, while the lung is clearly a target organ. Hypoproteinemia may be responsible for the early edema in soft tissues with sepsis.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004487:Edema / Q000139:chemically induced*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005402:Fistula; D007019:Hypoproteinemia / Q000503:physiopathology*; D008168:Lung / Q000502:physiology; D008208:Lymphatic System / Q000502:physiology; D008833:Microcirculation / Q000187:drug effects*; D012756:Sheep
D004731:Endotoxins