Effect of alpha-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat

1 The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-tr isphosphate) on oedema formation, microvascular protein leakage and interst itial fluid pressure (P-if) in rat skin after frostbite injury, was investi gated. alpha-Trinositol (40 mg kg body weight(-1)) was administered intrave nously as a bolus both before and/or in the interval between freezing and t hawing of the tissue. 2 P-if was measured in rat paw skin with micropipettes connected to a servo -controlled counterpressure system. Oedema formation was estimated by measu ring the increase in total tissue water content (wet weight minus dry weigh t divided by dry weight). Albumin extravasation (i.e., the difference betwe en the plasma equivalent space for I-125- and I-131-human serum albumin (HS A) circulating for different time intervals) was used to estimate the micro vascular leakage. 3 Compared to untreated animals, alpha-trinositol given pre- and/or post-fr eeze reduced total tissue water and albumin extravasation as well as the fa ll in P-if in injured tissue significantly (P<0.05). alpha-Trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46+/-0.93 and 2.37+/-1.12 to 2.51+/-0.29 and 0.36+/-0.18 ml g dry weight (-1), respectively (P<0.05). 4 P-if fell from -0.8 +/- 0.2 mmHg pre-freeze to -3.4 +/- 1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by t reatment with alpha-trinositol. 5 We conclude that alpha-trinositol exerts its anti-oedematous effect by ac ting on the extracellular matrix, attenuating the lowering of P-if as well as on the microvascular wall, thereby decreasing the protein extravasation.