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

Abstract

1 The anti-in¯ammatory eect of a-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial¯uid pressure (P if ) in rat skin after frostbite injury, was investigated. a-Trinositol (40 mg kg body weight 71 ) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing 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 measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the dierence between the plasma equivalent space for 125 I-and 131 I-human serum albumin (HSA) circulating for dierent time intervals) was used to estimate the microvascular leakage. 3 Compared to untreated animals, a-trinositol given pre-and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in P if in injured tissue signi®cantly (P50.05). aTrinositol 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 71 , respectively (P50.05). 4 P if fell from 70.8+0.2 mmHg pre-freeze to 73.4+1.0 mmHg (P50.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with a-trinositol. 5 We conclude that a-trinositol exerts its anti-oedematous eect by acting on the extracellular matrix, attenuating the lowering of P if as well as on the microvascular wall, thereby decreasing the protein extravasation.

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

“…Later experiments suggested that the P if reduction was associated with denaturation of collagen (276) and introduced the concept that the interstitium can "actively" contribute in P if regulation and thus enhance rather than prevent filtration. Such a mechanism of edema generation has later been confirmed in other burn injury models (245,428) and in frostbite injury (46). Although less pronounced, inflammation induced by a multitude of agents without simultaneous denaturation of collagen also resulted in P if reduction (for references, see Ref.…”

“…In rats, P i rose by 2 mmHg to approximately ϩ1 mmHg, and the compliance in hindlimb skin was almost infinite at a hydration 2-3 times control (504). In freeze injury, however, the volume-pressure relationship in rat paw skin was linear up to an overhydration of 140% with a corresponding C i of 6%/mmHg (46). A C i more than 50% lower than in dehydration in normal rats (504) suggests that the matrix is stiffer in this injury model, an assumption supported by the dramatic increase in P if that rose to 22 mmHg 60 min postfreeze (46).…”

“…A more pronounced increase in P if may occur if the edema formation is rapid, as shown by the increment in P if from Ϫ1 to 25 mmHg in rat frostbite injury (46) as the fluid volume increased to two to three times control (see sect. IVD).…”

“…In freeze injury, however, the volume-pressure relationship in rat paw skin was linear up to an overhydration of 140% with a corresponding C i of 6%/mmHg (46). A C i more than 50% lower than in dehydration in normal rats (504) suggests that the matrix is stiffer in this injury model, an assumption supported by the dramatic increase in P if that rose to 22 mmHg 60 min postfreeze (46). Interestingly, this study also indicated that C i may change with time due to stress relaxation as suggested by Guyton (170), since P if fell by 15 mmHg at constant tissue volume during the 60 min following placement of a tourniquet.…”

Part 13: First Aid

“…Evidence from 1 LOE 3 bench study 276 demonstrated elevated levels of inflammatory mediators in blister fluid of frostbite patients. In 6 LOE 5 animal studies, 264,[277][278][279][280][281] frostbite treatment that included administration of a nonsteroidal anti-inflammatory drug (NSAID) either before or following injury was beneficial. Two LOE 4 case series 273,282 reported healing without major tissue loss when an NSAID was included in treatment protocols, while 2 LOE 4 studies 271,283 did not clearly describe outcomes.…”