Microcircutation in burned wound and usefulness of microcirculation modulation

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1. The effects of microcirculation in a third degree burned wound in the early phase of burn on the integrity was studied by evaluating insensible water loss (ISWL) in 30% TBSA burned SD rat. The effects of cNOS inhibitor (N^G-nitro-L-arginine 10 mg/kg) and iNOS (aminoguanidine 100 mg/kg) on urinary NOx (=N02+N03) excretion and on ISWL were also examined. Urinary NOx was considered to be excreted dominantly by iNOS and iNOS inhibitor seemed to be beneficial to maintain the microcirculation in burned wound.2. To search a clinically available iNOS inhibitor, sepsis rat model induced by repeatedly (five times) injected endotoxin (5-10 mg/kg) for 100 minutes was used. FUT-175 (clinically used as a protease iinhibitor) was examined as to protect iNOS dependent organ (liver, lung and stomach) injuries. Endotoxemia increased plasma NOx levels from 19.4+/-2.1 micro MIL of control levels up to 36.0+/-4.1, and decreased down to 26.5+1-7.4 by FUT-175 (1-2 mg/kg x2) administration. cNOS in liver and lung increased in endotoxemia, and iNOS increased in all examined organs by injection of endotoxin. FUT-175 administration decreased the increased iNOS activities to control levels.3. iNOS seemed to be dominant both in the early phase and in septic phase of burn, and NO modulation by FUT-175 is considered useful for maintain circulation and protection organ function in burned patients.