Transvascular exchange and organ perfusion with reference to colloid and hypertonic solutions, and to endotoxaemia

Sammanfattning: Changes in vascular permeability can immensely change plasma volume and affect the degree of oedema in the body. In diseases with an increased vascular permeability, adequate fluid therapy is of considerable importance to prevent hypovolaemia. Mechanisms behind differences in effectiveness of various plasma volume expanders to restore a low plasma volume and a compromised microcirculation are still not fully understood. This thesis based on experimental studies on cat, analysis colloid and hypertonic plasma volume expanders regarding their effects on transvascular fluid exchange and vascular permeability in skeletal muscle during and after discontinuation of the infusions. In addition, permeability effects are analysed in skeletal muscle following endotoxin infusion, as well as effects of plasma volume substitution on intestinal perfusion and metabolism in endotoxaemia. The autoperfused right hind limb skeletal muscle was enclosed in a plethysmograph allowing continuous measurements of tissue volume variations. Capillary filtration coefficient measurements showed that fluid permeability is decreased by albumin and dextran, unchanged by hydroxyethyl starch (HES), and increased by gelatin. Measurements of change in the reflection coefficient for albumin showed no direct effect on albumin permeability of dextran, gelatin, or hydroxyethyl starch. Hypertonic saline increased fluid permeability an effect not seen with mannitol and urea. Muscle volume was decreased by 20% albumin, unchanged by 6% dextran 70 and 6% HES 200/0.5, and increased by 3.5% gelatin. Gelatin and HES, but not dextran and albumin induced rebound filtration, indicating interstitial accumulation of the colloid molecules. Hypertonic saline, mannitol and urea induced absorption of which hypertonic saline was most effective and mannitol less effective over time in relation to osmotic capacity. Mannitol and urea but not hypertonic saline showed rebound filtration indicating intracellular accumulation of mannitol and urea. During endotoxaemia, both fluid and albumin permeability increased in skeletal muscle and hypovolaemia was shown to be the major, but probably not the only cause of disturbed intestinal perfusion. No difference could be seen between albumin, dextran, and hydroxyethyl starch in effectiveness to restore intestinal perfusion during endotoxaemia.