Hemodilution with dextran: Effects on blood flow and thrombus formation. An experimental study in the rabbit

Sammanfattning: Microvascular surgery enables free tissue flaps to cover tissue defects, e.g. after trauma and malignancies. Although major improvements in techniques have been made, problems with poor tissue circulation and thrombus formation still exist. The aim of this thesis was to investigate the effects of hemodilution on tissue blood flow and thrombus formation in an animal model. In isovolemic hemodilution a defined volume of blood is replaced with an equal amount of an isoosmotic solution. This lowers hematocrit and blood viscosity. In paper I we demonstrated that hemodilution with dextran increased blood flow in the rabbit ear artery, showing that hemodilution improved perfusion of skin and subcutaneous tissue. The increase in blood flow occurred after a delay. In paper V it was found that hemodilution increased blood flow in aorta and vena cava instantaneously whereas flow to the hindlimbs and ear followed another time-course. Renal blood flow was little affected. In III, the influence of hemodilution on blood flow and function of striated muscle was examined. Hemodilution increased muscle force possibly due to an improved microcirculation. Inhibition of force during ischemia and the recovery of force and blood flow during reperfusion were not affected. A model for inserting small synthetic vascular (PTFE) grafts into the aorta was used in II. Hemodilution with dextran or albumin increased blood flow to equal extent but only dextran inhibited thrombus formation, reflecting that this compound has direct effects on the hemostasis, dissociated from its flow promoting properties. In IV and V, PTFE grafts were inserted in to the vena cava. These grafts occluded to a large extent in non-treated animals and the model provides interesting possibilities to study thrombus formation. Iso- or hypervolemic hemodilution with dextran strongly inhibited thrombus formation. The effects were not counteracted by desmopressin, which releases factors VIII and vWF, suggesting that the antithrombotic effects of dextran are not due to lowering the plasma concentration of these hemostatic factors. Heparin in a bolus dose strongly inhibited the thrombus formation underlining that the critical events for thrombus formation occur immediately after reperfusion. Hemodilution with hypertonic saline dextran (HSD) solutions markedly increased flow and strongly inhibited thrombus formation.