ALPHA-TRINOSITOL INHIBITS EDEMA GENERATION AND ALBUMIN EXTRAVASATION IN THERMALLY INJURED SKIN

Pharmacologic attempts to reduce edema generation and albumin extravasation into thermally injured skin have until recently been disappointing unless the drugs (usually antiphlogistic or anti-inflammatory drugs) were given before injury. We have studied the effect of alpha-trinositol (PP56, i.e., 1D-myo-inositol-1,2,6-trisphosphate) given after the injury in an experimental full-thickness 10% TBSA scald burn in anesthetized rats. Total tissue water content (TTW) and albumin extravasation (E(alb)) were determined in injured and noninjured skin (series I, n = 12). Interstitial fluid hydrostatic pressure (P(if)) was measured in injured skin (series II, n = 14). Alpha-trinositol was administered (alpha-trinositol groups) as an IV bolus (40 mg/kg) at 5 minutes after injury followed by an IV infusion (1.3 mg/kg/min). In both series a placebo group received burn injury and normal saline in equal volumes instead of alpha-trinositol. Compared with placebo, alpha-trinositol reduced TTW and E(alb) as well as the increased negativity of P(if) in injured tissue significantly. The effect on E(alb) was most prominent, with a reduction from 153.9 +/- 35.6 (SEM) muL/g in the NaCl group to 23.1 +/- 6.3 after alpha-trinositol (p < 0.005). Total tissue water was reduced from 2.51 +/- 0.13 to 2.17 +/- 0.06 mL/g (p < 0.05) and P(if) (measured between 21 and 40 minutes postinjury) from -24.7 +/- 4.1 to -3.2 +/- 1.1 mm Hg (p < 0.005). We conclude that alpha-trinositol markedly attenuates postburn edema formation by ameliorating both the burn-induced albumin leakage and the increased negativity in tissue pressure, the latter being a main driving force to explain the rapid formation of edema.