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The effect of substance P on sutured rat Achilles tendon rupture

Adelheid Steyaert UGent (2010)
abstract
Aim: To determine if the healing process of sutured rat Achilles tendon rupture could be stimulated by the paratendinous injection of substance P (SP). Methods: Ninety-six male Sprague-Dawley rats were randomly assigned to one of four groups and injected with saline, substance P (10-6 µmol/kg BW and 10-8 µmol/kg BW) associated with neutral endopeptidase inhibitors, or neutral endopeptidase inhibitors alone into the paratendinous region of the ruptured and subsequently sutured Achilles tendons from the second until the sixth day postoperatively. On days 7, 14, 28 and 42, animals were sacrificed. A histological, biomechanical and immunofluoresence study was performed to evaluate fibroblast proliferation, angiogenesis, collagenorganization, stress at maximal load, work to maximal load, stiffness and SP, NK-1 receptor, and PGP 9.5 expression resp. Results: The two groups subjected to SP injections showed a significant initial fibroblast and capillary proliferation on day 7, which rapidly declined by day 14. Collagen orientation increased faster in the groups injected with SP from the second week already and the difference remained until the completion of the study. Stress at maximal load was significantly higher in the groups injected with SP in weeks one, two, and six compared to the saline group. Work to maximal load was significantly higher in the SP groups than in the saline group in weeks two, four, and six. Stiffness did not differ between any of the groups during the study. In all groups SP, was predominantly expressed in the extracellular matrix during the first two weeks and disappeared progressively afterwards. In contrast, SP was not expressed in the blood vessel wall during the first two weeks. NK-1 receptor was almost always expressed in the blood vessel wall and in the extracellular matrix during this period and disappeared progressively afterwards. No nerve ingrowth could be demonstrated. Conclusion: Exogenously administered SP has a positive effect on fibroblast proliferation and angiogenesis in ruptured and subsequently sutured rat Achilles tendons. Moreover, it is likely to have a booster effect on fibroblast proliferation via autocrine and paracrine secretion of SP. There also was a positive effect on collagen orientation, which was reflected in the biomechanical variables of stress at maximal load and work to maximal load.
Please use this url to cite or link to this publication:
author
promoter
UGent
organization
year
type
dissertation
publication status
published
subject
keyword
healing, Achilles tendon rupture, rat, biomechanics, substance P
pages
125 pages
publisher
Ghent University. Faculty of Medicine and Health Sciences
place of publication
Ghent, Belgium
defense location
Gent : UZ (auditorium C)
defense date
2010-01-27 17:00
language
English
UGent publication?
yes
classification
D1
additional info
dissertation in parts contains copyrighted material
copyright statement
I have transferred the copyright for this publication to the publisher
id
922767
handle
http://hdl.handle.net/1854/LU-922767
date created
2010-04-09 15:02:02
date last changed
2017-01-16 10:53:53
@phdthesis{922767,
  abstract     = {Aim: To determine if the healing process of sutured rat Achilles tendon rupture could be stimulated by the paratendinous injection of substance P (SP).
Methods: Ninety-six male Sprague-Dawley rats were randomly assigned to one of four groups and injected with saline, substance P (10-6 {\textmu}mol/kg BW and 10-8 {\textmu}mol/kg BW) associated with neutral endopeptidase inhibitors, or neutral endopeptidase inhibitors alone into the paratendinous region of the ruptured and subsequently sutured Achilles tendons from the second until the sixth day postoperatively. On days 7, 14, 28 and 42,  animals were sacrificed. A  histological, biomechanical and immunofluoresence study was performed to evaluate fibroblast proliferation, angiogenesis, collagenorganization, stress at maximal load, work to maximal load, stiffness and SP, NK-1 receptor, and PGP 9.5 expression resp.
Results: The two groups subjected to SP injections showed a significant initial fibroblast and capillary proliferation on day 7, which rapidly declined by day 14. Collagen orientation increased faster in the groups injected with SP from the second week already and the difference remained until the completion of the study.
Stress at maximal load was significantly higher in the groups injected with SP in weeks one, two, and six compared to the saline group. Work to maximal load was significantly higher in the SP groups than in the saline group in weeks two, four, and six. Stiffness did not differ between any of the groups during the study.
In all groups SP, was predominantly expressed in the extracellular matrix during the first two weeks and disappeared progressively afterwards. In contrast, SP was not expressed in the blood vessel wall during the first two weeks. NK-1 receptor was almost always expressed in the blood vessel wall and in the extracellular matrix during this period and disappeared progressively afterwards. No nerve ingrowth could be demonstrated. 
Conclusion: Exogenously administered SP has a positive effect on fibroblast proliferation and angiogenesis in ruptured and subsequently sutured rat Achilles tendons. Moreover, it is likely to have a booster effect on fibroblast proliferation via autocrine and paracrine secretion of SP. There also was a positive effect on collagen orientation, which was reflected in the biomechanical variables of stress at maximal load and work to maximal load.},
  author       = {Steyaert, Adelheid},
  keyword      = {healing,Achilles tendon rupture,rat,biomechanics,substance P},
  language     = {eng},
  pages        = {125},
  publisher    = {Ghent University. Faculty of Medicine and Health Sciences},
  school       = {Ghent University},
  title        = {The effect of substance P on sutured rat Achilles tendon rupture},
  year         = {2010},
}

Chicago
Steyaert, Adelheid. 2010. “The Effect of Substance P on Sutured Rat Achilles Tendon Rupture”. Ghent, Belgium: Ghent University. Faculty of Medicine and Health Sciences.
APA
Steyaert, A. (2010). The effect of substance P on sutured rat Achilles tendon rupture. Ghent University. Faculty of Medicine and Health Sciences, Ghent, Belgium.
Vancouver
1.
Steyaert A. The effect of substance P on sutured rat Achilles tendon rupture. [Ghent, Belgium]: Ghent University. Faculty of Medicine and Health Sciences; 2010.
MLA
Steyaert, Adelheid. “The Effect of Substance P on Sutured Rat Achilles Tendon Rupture.” 2010 : n. pag. Print.