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-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. 2. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. 3. Compared to untreated animals, alpha-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif 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. Pif 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 treatment with alpha-trinositol. 5. We conclude that alpha-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation.