Plasma hyaluronan and hemorheology in patients with septic shock: A clinical and experimental study

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BACKGROUND: Total plasma hyaluronan concentration is increased in septic shock. High-molecular-weight hyaluronan has a high intrinsic viscosity. Excessive release of high-molecular-weight hyaluronan in sepsis may induce hyperviscosity. METHODS: Plasma viscosity and the molecular size of plasma hyaluronan were determined in 20 patients with septic shock and in 20 healthy controls. Ex vivo, the effects of 0.4% and 0.047% high-molecular-weight hyaluronan 1560 kDa, 0.9% saline, and 6% hydroxy-ethyl-starch 130 kDa were compared to plasma and whole blood viscosity and red blood cell aggregation at a systemic hematocrit of 0.4, and at a microcirculatory hematocrit of 0.2. RESULTS: Plasma viscosity and total plasma protein content were low in septic shock patients on days one and four of treatment. Hyaluronan concentration was 10-fold higher in sepsis on day 1. Molecular weight of hyaluronan was relatively low, mostly 50-500 kDa, and did not change significantly in sepsis. Ex vivo, 0.4% high-molecular-weight hyaluronan 1560 kDa increased blood viscosity but did not promote red blood cell aggregation. Dilutions of 6% hydroxyl-ethyl-starch 130 kDa and 0.047% high-molecular-weight hyaluronan 1560 kDa had comparable effects on blood viscosity and red blood cell aggregation. CONCLUSIONS: Plasma viscosity of the septic patients remained low for four days despite markedly elevated concentration of relatively small-molecular-weight hyaluronan.