Physiological and clinical aspects of change in microvascular permeability

Microvascular permeability is important for exchange of fluids and proteins in health and in disease. Permeability increases in critical illness, such as during sepsis/SIRS and after trauma, and may be affected by drugs. Increased permeability causes oedema and hypovolaemia. Hypovolaemia is treated with fluids, and their efficacy is determined by their intravascular retention, also influenced by the prevailing permeability. Permeability changes in some of these situations are evaluated in the present thesis.The effects of endogenous NO and prostacyclin on microvascular permeability were analysed, and we found that they reduce fluid and protein permeability, and conclude that dynamic release of NO and prostacyclin may exert bi-directional regulation of permeability.We also found that exercise decreased fluid permeability in skeletal muscle by release of NO, reducing the exercise-induced oedema. Neither NO nor prostacyclin are responsible for exercise hyperaemia.We found that the anti-hypertensive vasopeptidase inhibitor omapatrilat, combining ACE- and NEP-inhibition, increases fluid and protein permeability through increased bradykinin in plasma due to NEP inhibition, a mechanism that may explain the angiooedema sometimes seen with omapatrilat treatment.After haemorrhage on rat with a relatively normal permeability, 5% albumin, 4% gelatin and 6% hydroxyethyl starch (HES) 130/0.4, saline and retransfusion of erythrocytes all had satisfactory plasma volume expanding effects, but albumin was superior the other solutions. After trauma on cat, where permeability was increased, 6% dextran 70 most likely preserved plasma volume better than 5% albumin, which was better than 3.5% gelatin, 6% HES 130/0.4 and saline. These results indicate that the efficacy of colloids as plasma volume expanders is determined by the prevailing microvascular permeability.