title: Arteriolovenular shunting critically determines shutdown of microcirculation upon cryotherapy in tumor-bearing rat liver.
abstract: BACKGROUND
  Tissue destruction by cryosurgery not only is mediated by direct cell damage, but also involves secondary mechanisms, such as ischemia due to shutdown of the microcirculation. Clinicians favor repetitive cryoapplication, although there is no proven evidence for a more effective tumor eradication.
  
  
  METHODS
  The aims of this study were (1) to establish a rat liver tumor model that allows for intravital microscopic analysis of hepatic tumor microcirculation and (2) to elucidate critical determinants of shutdown of microvascular perfusion after single and repetitive cryotherapy. In WAG-Rji rats (n = 14), syngeneic colon carcinoma cells (CC531) were implanted into the left liver lobe. Hepatic and tumor microcirculation were studied by intravital microscopy.
  
  
  RESULTS
  Two weeks after implantation, the tumors had developed a microvasculature with a capillary density markedly (P < .05) lower compared with the sinusoidal density of normal liver. However, at the tumor margin, venule diameters were significantly enlarged (P < .05), with high red blood cell velocities and arteriolovenular shunts. Both freeze procedures (temperature at the tumor margin: -32.4 degrees C +/- 1.6 degrees C and -36.4 degrees C +/- 2.0 degrees C) resulted in a complete shutdown of intratumoral and peritumoral capillary and hepatic sinusoidal perfusion. In contrast, some large venules showed maintenance of blood flow initially after freezing (15 minutes); however, this was abolished during the subsequent 2-hour observation period.
  
  
  CONCLUSIONS
  Enlarged high-flow venules at the tumor margin, which participate in arteriolovenular shunting, critically determine the shutdown of the microcirculation upon cryotherapy. Repetitive freezing is not more effective than a single-freeze procedure to achieve complete tumor microcirculatory stasis.
authors.affiliation: Department for General, Visceral, and Vascular Surgery, University of Saarland, D-66421, Homburg/Saar, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Georg
authors.initials: G
authors.lastname: Pistorius
authors.forename: Roland
authors.initials: R
authors.lastname: Seidel
authors.forename: Gernot
authors.initials: G
authors.lastname: Feifel
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D001163:Arteriovenous Anastomosis; D003110:Colonic Neoplasms / Q000473:pathology*; D003452:Cryosurgery / Q000379:methods*; D004195:Disease Models, Animal; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured