Effect of alpha-trinositol on interstitial fluid pressure, edema generation, and albumin extravasation after ischemia-reperfusion injury in rat hind limb.
Reperfusion of ischemic tissue often leads to an acute inflammatory response, which acts directly to aggravate the injury in the reperfused zone, characterized by adhesion and subsequent infiltration of inflammatory cells that injure the tissue through the generation of oxygen-derived free radicals and release of various inflammatory mediators. The rapid edema formation associated with reperfusion injury is induced by increased microvascular permeability to plasma proteins and/or increased net filtration pressure across the microvascular wall, and the latter is at least in part induced by lowering of the interstitial fluid pressure (P(if)). We investigated the anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on edema formation, microvascular protein leakage, and P(if) in rat hind limb after ischemia-reperfusion (I/R) injury. There was significant increase of both albumin extravasation from 0.02 +/- 0.02 to 0.41 +/- 0.21 mL g dry weight-1 (P < 0.05) and total tissue water from 1.08 +/- 0.07 to 1.65 +/- 0.55 mL g dry weight(-1) (P < 0.05) in the skin of paws undergoing I/R injury. P(if) was significantly lowered from -0.51 +/- 0.34 to -5.00 +/- 1.53 mmHg (P < 0.05) concomitant with substantial edema formation. The edema formation, and lowering of P(if) during I/R injury was significantly lowered and nearly totally abolished in the animals treated with alpha-trinositol 30 min before reperfusion. We conclude that alpha-trinositol limits the increased vascular permeability and edema formation by preventing the decrease in P(if) as well as acting protective on the microvascular wall.
Nedrebø
Torbjørn
T
Department of Physiology, University of Bergen, Bergen, Norway.
Reed
Rolf K
RK
Berg
Ansgar
A
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006614:Hindlimb / Q000293:injuries* / Q000473:pathology; D007249:Inflammation; D007295:Inositol Phosphates / Q000494:pharmacology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013997:Time Factors
D000418:Albumins; D000893:Anti-Inflammatory Agents; D007295:Inositol Phosphates; C059368:atrinositol