title: High dose vitamin C counteracts the negative interstitial fluid hydrostatic pressure and early edema generation in thermally injured rats.
abstract: OBJECTIVE
  edema formation after thermal injury is rapid and fulminant within the first hour after injury and increased microvascular permeability has been claimed to be the main responsible mechanism. An acute decrease in interstitial fluid hydrostatic pressure (P(if)) down to -150 mm Hg has recently been reported in dermal burns. This strong negative tissue pressure creates a 'suction' on the fluid in the capillaries. Furthermore, high dose vitamin C (VC) has been shown to reduce postburn edema and fluid requirements following major burn injuries. This led to the present study, aimed at investigating whether VC administered after thermal injury in rats, could attenuate the strongly negative P(if). Edema volume was measured by total tissue water content (TTW) and extravasation of albumin (Ealb).
  
  
  METHODS
  a prospective, open experimental study.
  
  
  METHODS
  pentobarbital-anesthetized rats received either a full-thickness burn injury covering 10% of total body surface area, or a sham burn. The rats were given VC or equal volumes normal saline (NS) either before the burn, 5 or 30 min after the injury. VC (25 mg/ml in NS, osmolality 272 mOsm/l) was administered as a bolus (66 mg/kg) followed by infusion (33 mg/kg/h). The animals were divided into 7 groups (6 animals in each) according to the timing of VC/NS administration: (1) VC-preburn, (2) VC-5 min postburn, (3) VC-30 min postburn, (4) NS-preburn, (5) NS-5 min postburn, (6) NS-30 min postburn and (7) VC-pre sham burn group. All groups were duplicated for series I and II.
  
  
  METHODS
  in series I; P(if) was measured using a sharpened glass micropipette connected to a servo-controlled counter pressure system. Measurements were averaged in the following time periods: preburn, 5-20, 21-40, 41-60 and 61-90 min postburn. In series II; Ealb and TTW were measured in burned and non-burned skin by radio-labelled albumin and wet-dry weights, respectively.
  
  
  RESULTS
  in the sham control group (VC-pre-sham burn), P(if) ranged between -1 and -2 mm Hg and did not change throughout the experimental period. In the NS group (placebo), P(if) fell to -46.8 +/- 10.1 (1 S.D.) mm Hg at 5-20 min after the injury and were -23.1 +/- 13.4 and -11.6 +/- 4.1 mm Hg at 21-40 and 41-60 min postburn. P(if) returned to preburn values at 61-90 min post injury. In the VC groups, there was a marked attenuation of the negative P(if) to average -10.1 +/- 11.8 mm Hg at 5-20 min, -2 +/- 1.7 and -0.6 +/- 1.2 mm Hg at 21-40 and 41-60 min after injury, respectively (all p < 0.01 compared to NS). TTW in burned skin of the NS-5 min groups was 3.12 +/- 0.28, VC5-min group was 2.57+/-0.69 and VC sham was 1.77+/-0.19 ml/g DW, respectively (p < 0.01 compared to sham control for all values). In all the VC-groups TTW values were higher than sham control and lower than in the corresponding NS-groups (p > 0.05 both ways). No statistical significant differences were found between Ealb-values in the VC- and NS-groups.
  
  
  CONCLUSIONS
  high-dose vitamin C attenuates the development of strongly negative P(if) in burned dermis and reduces the edema as measured by TTW. No significant change in Ealb was found. Vitamin C was thus found to have potential beneficial effects on the acute postburn edema generation.
authors.affiliation: Department of Traumatology and CCM, Kyorin University, Mitaka, Tokyo, Japan. htanaka@tccm.kyorin-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Lund
authors.forename: H
authors.initials: H
authors.lastname: Wiig
authors.forename: R K
authors.initials: RK
authors.lastname: Reed
authors.forename: T
authors.initials: T
authors.lastname: Yukioka
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: S
authors.initials: S
authors.lastname: Shimazaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D002056:Burns / Q000150:complications*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy* / Q000209:etiology; D005110:Extracellular Space / Q000187:drug effects; D006874:Hydrostatic Pressure; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D001205:Ascorbic Acid