title: The role of the veno-arteriolar reflex (VAR) in the pathogenesis of peripheral oedema in patients with chronic critical limb ischaemia (CLI).
abstract: OBJECTIVE
  Relatively many patients with chronic critical limb ischaemia (CLI) have oedema in the afflicted limb. Previous studies in these patients indicate derangement in the Starling forces governing transcapillary fluid balance. An impaired veno-arteriolar reflex (VAR) may cause an increase in capillary pressure and hence increased filtration pressure resulting in oedema. The aim of the present study was to investigate VAR in patients with CLI to come to a better understanding of the pathogenesis of ischaemic oedema.
  
  
  METHODS
  Sixteen patients (mean age of 78+/-9.4 years) with unilateral CLI and oedema were included. There were two control groups of similar age, one consisted of 8 patients with unilateral CLI but without oedema and the other of 9 healthy subjects. Laser Doppler fluxmeters were used to evaluate the foot skin microcirculation, with the limbs in supine as well as in the dependent position, simultaneously in 4 different areas: the pulp of the first toe (Sitel), at the level of the second metatarsal body (Site 2), at the anterolateral part of ankle (Site 3) and the pulp of the first toe of the contralateral limb (Site 4) as reference. Laser Doppler flux (LDF) values (expressed in perfusion unit, PU) were recorded with the foot dependent (PUd), in the horizontal position (PUh), and the orthostatic response (OR) was calculated at all measuring sites as PUd/PUh.
  
  
  RESULTS
  In none of the measured sites there was a significant difference in OR between the limbs with CLI and oedema and the limbs with CLI but without oedema. The median OR of CLI limbs at site 1 [2.5 (0.61-8.96)] was greater than at sites 2 [0.99 (0.46-2.38), p < 0.01] and 3 [0.95 (0.68-10.31), p < 0.04] respectively, while the differences in OR between site 2 and 3 were not significant. The median OR in the limbs of healthy controls at sites 1, 2 and 3 were 0.58 (0.37-1.43), 0.54 (0.28-1.33) and 0.51 (0.34-0.91), respectively. There were no significant differences in OR between sites 1, 2 and 3 of the control group. The OR of CLI at site 1, 2 and 3 were significantly greater than the corresponding sites in the healthy subjects (p < 0.001, p < 0.008, p < 0.001).
  
  
  CONCLUSIONS
  The VAR is disturbed in limbs with CLI, both in the ones with and without oedema. There were regional differences in the OR in these ischaemic feet but there were no differences in OR between those with and without oedema. Thus, disturbances in VAR may play a role in the development of ischaemic oedema, but is probably not the only causative factor.
authors.affiliation: Department of Vascular Diagnosis and Research, Aker Hospital, University of Oslo, Norway. m.d.anvar@ioks.uio.no
authors.forename: H Z
authors.initials: HZ
authors.lastname: Khiabani
authors.forename: M D
authors.initials: MD
authors.lastname: Anvar
authors.forename: A J
authors.initials: AJ
authors.lastname: Kroese
authors.forename: E
authors.initials: E
authors.lastname: Stranden
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004487:Edema / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D007866:Leg / Q000098:blood supply*; D008297:Male; D011187:Posture; D012018:Reflex / Q000502:physiology*; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*