title: Effects of intravascular cryotherapy on vessel wall repair in a balloon-injured rabbit iliac artery model.
abstract: OBJECTIVE
  Although the application of cold energy, cryotherapy, has been shown to cause selective damage to cellular components with preservation of matrix structure resulting in less fibrosis in a variety of tissues, the effects of intravascular cryotherapy on vessel wall repair after balloon angioplasty are unknown. We sought to characterize the effects of cryotherapy application on vessel wall repair after balloon angioplasty and study the relationship between collagen accumulation in the vessel wall and late lumen loss as assessed by serial intravascular ultrasound.
  
  
  METHODS
  The immediate, early (72 h) and late (10 weeks) effects of three intravascular cryotherapy application time periods (60, 120 and 240 s) after iliac artery balloon angioplasty ('cryotherapy') were compared with balloon angioplasty alone ('control') in 59 rabbits. Arterial lumen area was measured by intravascular ultrasound immediately after the procedure, at 72 h and at 10 weeks. Collagen content was calculated separately for intima and media/adventitia layers and correlated with late lumen loss.
  
  
  RESULTS
  Cryotherapy produced average vessel wall temperature of -26 degrees C (range, -20 to -45 degrees C) and resulted in significantly larger lumen cross-sectional area (CSA) immediately after application (5.74+/-1.18 vs. 4.14+/-0.75 mm(2), P=0.008) but was not different than control arteries at 10 weeks. At 72 h, there was extensive cell loss in the medial and adventitial layers accompanied by increased macrophage infiltration in cryotherapy treated arteries compared to control. At 10 weeks, intimal hyperplasia was increased 2-fold in cryotherapy treated arteries. Collagen content was increased 2-fold in the medial/adventitial layers, and nearly 3-fold in the intima of cryotherapy treated arteries. Collagen content in arterial intima (P=0.01) as well as media/adventitia (P=0.005) positively correlated with late lumen loss. Foci of chondro- and osseous metaplasia and calcification were evident at the medial-adventitial junction in cryotherapy treated arteries at 10 weeks.
  
  
  CONCLUSIONS
  Intravascular cryotherapy induced early arterial wall cell loss and late intimal hyperplasia, vascular fibrosis and chondro- and osseous metaplastic changes with no late beneficial effects on lumen area compared to balloon angioplasty alone. Collagen accumulation in all three layers of the vessel wall contributes to the development of late inward remodeling after balloon angioplasty.
authors.affiliation: The Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8.
authors.forename: Asim N
authors.initials: AN
authors.lastname: Cheema
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Nili
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Li
authors.forename: Heather A
authors.initials: HA
authors.lastname: Whittingham
authors.forename: Jacek
authors.initials: J
authors.lastname: Linde
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Suylen
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Eskandarian
authors.forename: Amy P
authors.initials: AP
authors.lastname: Wong
authors.forename: Beiping
authors.initials: B
authors.lastname: Qiang
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Mimi
authors.initials: M
authors.lastname: Lane
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
mesh_terms: D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division; D003094:Collagen / Q000032:analysis; D017679:Cryotherapy / Q000379:methods*; D004549:Elastin / Q000032:analysis; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000293:injuries* / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D011817:Rabbits; D018084:Ultrasonography, Interventional
chemical_list: D003094:Collagen; D004549:Elastin; D053148:Caspase 3; D020169:Caspases