Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model

Ralf G. Seipelt, Carl L. Backer, Constantine Mavroudis, Veronica Stellmach, Ingrid M. Seipelt, Mona Cornwell, Jose Hernandez, Susan E. Crawford

Research output: Contribution to journalArticle

Abstract

Background - Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. Methods and Results - In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n= 15), resection of an aortic ring (tension; n = 14) or resection and topical VEGF treatment (0.75 μg VEGF165; tension+VEGF; n= 14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at I month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group). Conclusions - In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.

Original languageEnglish (US)
JournalCirculation
Volume108
Issue number10 SUPPL.
StatePublished - Sep 9 2003
Externally publishedYes

Fingerprint

Aortic Coarctation
Vascular Endothelial Growth Factor A
Thorax
Rabbits
Blood Vessels
Pathologic Constriction
Fibrosis
Metaplasia
Arterial Pressure

Keywords

  • Aorta
  • Coarctation
  • Growth factors
  • Remodeling
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Seipelt, R. G., Backer, C. L., Mavroudis, C., Stellmach, V., Seipelt, I. M., Cornwell, M., ... Crawford, S. E. (2003). Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model. Circulation, 108(10 SUPPL.).

Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model. / Seipelt, Ralf G.; Backer, Carl L.; Mavroudis, Constantine; Stellmach, Veronica; Seipelt, Ingrid M.; Cornwell, Mona; Hernandez, Jose; Crawford, Susan E.

In: Circulation, Vol. 108, No. 10 SUPPL., 09.09.2003.

Research output: Contribution to journalArticle

Seipelt, RG, Backer, CL, Mavroudis, C, Stellmach, V, Seipelt, IM, Cornwell, M, Hernandez, J & Crawford, SE 2003, 'Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model', Circulation, vol. 108, no. 10 SUPPL..
Seipelt RG, Backer CL, Mavroudis C, Stellmach V, Seipelt IM, Cornwell M et al. Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model. Circulation. 2003 Sep 9;108(10 SUPPL.).
Seipelt, Ralf G. ; Backer, Carl L. ; Mavroudis, Constantine ; Stellmach, Veronica ; Seipelt, Ingrid M. ; Cornwell, Mona ; Hernandez, Jose ; Crawford, Susan E. / Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model. In: Circulation. 2003 ; Vol. 108, No. 10 SUPPL.
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abstract = "Background - Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. Methods and Results - In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n= 15), resection of an aortic ring (tension; n = 14) or resection and topical VEGF treatment (0.75 μg VEGF165; tension+VEGF; n= 14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29{\%} versus 19{\%}; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at I month (P<0.05) and luminal area was only reduced 3{\%} at 2 months (P<0.001 versus tension group). Conclusions - In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.",
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T1 - Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model

AU - Seipelt, Ralf G.

AU - Backer, Carl L.

AU - Mavroudis, Constantine

AU - Stellmach, Veronica

AU - Seipelt, Ingrid M.

AU - Cornwell, Mona

AU - Hernandez, Jose

AU - Crawford, Susan E.

PY - 2003/9/9

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N2 - Background - Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. Methods and Results - In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n= 15), resection of an aortic ring (tension; n = 14) or resection and topical VEGF treatment (0.75 μg VEGF165; tension+VEGF; n= 14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at I month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group). Conclusions - In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.

AB - Background - Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. Methods and Results - In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n= 15), resection of an aortic ring (tension; n = 14) or resection and topical VEGF treatment (0.75 μg VEGF165; tension+VEGF; n= 14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at I month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group). Conclusions - In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.

KW - Aorta

KW - Coarctation

KW - Growth factors

KW - Remodeling

KW - Restenosis

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