Skip to main content
Erschienen in: Surgical Endoscopy 5/2016

12.08.2015

Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair

verfasst von: Job C. Tharappel, Jennifer W. Harris, Brittany A. Zwischenberger, Salomon M. Levy, David A. Puleo, J. Scott Roth

Erschienen in: Surgical Endoscopy | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats.

Study design

Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting.

Results

In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control.

Conclusion

It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.
Literatur
1.
Zurück zum Zitat Rutkow IM, Robbins AW (1993) Demographic, classificatory, and socioeconomic aspects of hernia repair in the United States. Surg Clin N Am 73:413–426PubMed Rutkow IM, Robbins AW (1993) Demographic, classificatory, and socioeconomic aspects of hernia repair in the United States. Surg Clin N Am 73:413–426PubMed
3.
Zurück zum Zitat Mudge M, Hughes LE (1985) Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg 72:70–71CrossRefPubMed Mudge M, Hughes LE (1985) Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg 72:70–71CrossRefPubMed
4.
Zurück zum Zitat George CD, Ellis H (1986) The results of incisional hernia repair: a twelve year review. Ann R Coll Surg Engl 68:185–187PubMedPubMedCentral George CD, Ellis H (1986) The results of incisional hernia repair: a twelve year review. Ann R Coll Surg Engl 68:185–187PubMedPubMedCentral
5.
Zurück zum Zitat Langer S, Christiansen J (1985) Long-term results after incisional hernia repair. Acta Chir Scand 151:217–219PubMed Langer S, Christiansen J (1985) Long-term results after incisional hernia repair. Acta Chir Scand 151:217–219PubMed
6.
Zurück zum Zitat Anthony T, Bergen PC, Kim LT (2000) Factors affecting recurrence following incisional herniorrhaphy. World J Surg 24:95–101CrossRefPubMed Anthony T, Bergen PC, Kim LT (2000) Factors affecting recurrence following incisional herniorrhaphy. World J Surg 24:95–101CrossRefPubMed
7.
Zurück zum Zitat Leber GE, Garb JL, Alexander AJ, Reed WP (1998) Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378–382CrossRefPubMed Leber GE, Garb JL, Alexander AJ, Reed WP (1998) Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378–382CrossRefPubMed
9.
Zurück zum Zitat Salameh JR, Talbott LM, May W, Gosheh B, Vig PJ, McDaniel DO (2007) Role of biomarkers in incisional hernias. Am Surg 73:561–567; discussion 567–568 Salameh JR, Talbott LM, May W, Gosheh B, Vig PJ, McDaniel DO (2007) Role of biomarkers in incisional hernias. Am Surg 73:561–567; discussion 567–568
10.
Zurück zum Zitat Antoniou SA, Antoniou GA, Granderath FA, Simopoulos C (2009) The role of matrixmetallo-proteinases in the pathogenesis of abdominal wall hernias. Eur J Clin Invest 39:953–959CrossRefPubMed Antoniou SA, Antoniou GA, Granderath FA, Simopoulos C (2009) The role of matrixmetallo-proteinases in the pathogenesis of abdominal wall hernias. Eur J Clin Invest 39:953–959CrossRefPubMed
11.
Zurück zum Zitat Lee HM, Ciancio SG, Tüter G, Ryan ME, Komaroff E, Golub LM (2004) Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal antiinflammatory drug. J Periodontol 75:453–463CrossRefPubMed Lee HM, Ciancio SG, Tüter G, Ryan ME, Komaroff E, Golub LM (2004) Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal antiinflammatory drug. J Periodontol 75:453–463CrossRefPubMed
12.
Zurück zum Zitat Tharappel JC, Bower CE, Whittington-Harris J, Ramineni SK, Puleo DA, Roth JS (2014) Doxycycline administration improves fascial interface in hernia repair. J Surg Res 190:692–698CrossRefPubMed Tharappel JC, Bower CE, Whittington-Harris J, Ramineni SK, Puleo DA, Roth JS (2014) Doxycycline administration improves fascial interface in hernia repair. J Surg Res 190:692–698CrossRefPubMed
13.
Zurück zum Zitat Tharappel JC, Ramineni SK, Reynolds D, Puleo DA, Roth JS (2013) Doxycycline impacts hernia repair outcomes. J Surg Res 184:699–704CrossRefPubMed Tharappel JC, Ramineni SK, Reynolds D, Puleo DA, Roth JS (2013) Doxycycline impacts hernia repair outcomes. J Surg Res 184:699–704CrossRefPubMed
14.
Zurück zum Zitat Rice RD, Ayubi FS, Shaub ZJ, Parker DM, Armstrong PJ, Tsai JW (2010) Comparison of Surgisis, AlloDerm, and Vicryl woven mesh grafts for abdominal wall defect repair in an animal model. Aesth Plast Surg 34:290–296CrossRef Rice RD, Ayubi FS, Shaub ZJ, Parker DM, Armstrong PJ, Tsai JW (2010) Comparison of Surgisis, AlloDerm, and Vicryl woven mesh grafts for abdominal wall defect repair in an animal model. Aesth Plast Surg 34:290–296CrossRef
15.
Zurück zum Zitat White AC, Hayat CS, Kimball KT (1987) Effects of lipophilic tetracyclines against Giardia lamblia. J Infect Dis 28:781–787 White AC, Hayat CS, Kimball KT (1987) Effects of lipophilic tetracyclines against Giardia lamblia. J Infect Dis 28:781–787
16.
Zurück zum Zitat Sezaki M, Inouye S, Kondo S (1992) A new tetracycline antibiotic with antitumor activity. I. Taxonomy and fermentation of the producing strain, isolation and characterization of SF-2575. J Antibiotics 45:320–324CrossRef Sezaki M, Inouye S, Kondo S (1992) A new tetracycline antibiotic with antitumor activity. I. Taxonomy and fermentation of the producing strain, isolation and characterization of SF-2575. J Antibiotics 45:320–324CrossRef
17.
Zurück zum Zitat Flanigan TP, Soave R (1991) Plasmodium falciparum growth and the effects of chlortetracycline. Clin Infect Dis 63:388–392 Flanigan TP, Soave R (1991) Plasmodium falciparum growth and the effects of chlortetracycline. Clin Infect Dis 63:388–392
18.
Zurück zum Zitat Castro MM, Tanus-Santos JE (2013) Inhibition of matrix metalloproteinases (MMPs) as a potential strategy to amelioratehypertension-induced cardiovascular alterations. Curr Drug Targets 14:335–343PubMed Castro MM, Tanus-Santos JE (2013) Inhibition of matrix metalloproteinases (MMPs) as a potential strategy to amelioratehypertension-induced cardiovascular alterations. Curr Drug Targets 14:335–343PubMed
19.
Zurück zum Zitat Antonio RC, Ceron CS, Rizzi E, Coelho EB, Tanus-Santos JE, Gerlach RF (2014) Antioxidant effect of doxycycline decreases MMP activity and blood pressure in SHR. Mol Cell Biochem 386:99–105CrossRefPubMed Antonio RC, Ceron CS, Rizzi E, Coelho EB, Tanus-Santos JE, Gerlach RF (2014) Antioxidant effect of doxycycline decreases MMP activity and blood pressure in SHR. Mol Cell Biochem 386:99–105CrossRefPubMed
20.
Zurück zum Zitat Wysocki AB, Staiano-Coico L, Grinnell F (1993) Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 101:64–68CrossRefPubMed Wysocki AB, Staiano-Coico L, Grinnell F (1993) Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 101:64–68CrossRefPubMed
21.
22.
Zurück zum Zitat Mignatti P, Rifkin DB, Welgus HG, Parks WC (1996) Proteinases and tissue remodeling. In: Clark RAF (ed) The molecular and cellular biology of wound repair, 2nd edn. Plenum Press, New York, pp 427–474 Mignatti P, Rifkin DB, Welgus HG, Parks WC (1996) Proteinases and tissue remodeling. In: Clark RAF (ed) The molecular and cellular biology of wound repair, 2nd edn. Plenum Press, New York, pp 427–474
23.
Zurück zum Zitat Murphy G, Willenbrock F, Crabbe T, O’Shea M, Ward R, Atkinson S, O’Connell J, Docherty A (1994) Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci 732:31–41CrossRefPubMed Murphy G, Willenbrock F, Crabbe T, O’Shea M, Ward R, Atkinson S, O’Connell J, Docherty A (1994) Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci 732:31–41CrossRefPubMed
24.
Zurück zum Zitat Smith APS (2003) The role of MMPs in chronic wound edema. Podiatry Today 16:22–26 Smith APS (2003) The role of MMPs in chronic wound edema. Podiatry Today 16:22–26
25.
Zurück zum Zitat Wilcox JR, Covington DS, Paez N (2012) Doxycycline as a modulator of inflammation in chronic wounds. Wounds 24:339–349PubMed Wilcox JR, Covington DS, Paez N (2012) Doxycycline as a modulator of inflammation in chronic wounds. Wounds 24:339–349PubMed
27.
Zurück zum Zitat Lorenzl S, Albers DS, Narr S, Chirichigno J, Beal MF (2002) Expression of MMP-2, MMP-9, and MMP-1 and their endogenous counterregulators TIMP-1 and TIMP-2 in postmortem brain tissue of Parkinson’s disease. Exp Neurol 178:13–20CrossRefPubMed Lorenzl S, Albers DS, Narr S, Chirichigno J, Beal MF (2002) Expression of MMP-2, MMP-9, and MMP-1 and their endogenous counterregulators TIMP-1 and TIMP-2 in postmortem brain tissue of Parkinson’s disease. Exp Neurol 178:13–20CrossRefPubMed
28.
Zurück zum Zitat Guedez L, Courtemanch L, Stetler-Stevenson M (1998) Tissue inhibitor of metalloproteinase (TIMP)-1 induces differentiation and an antiapoptotic phenotype in germinal center B cells. Blood 92:1342–1349PubMed Guedez L, Courtemanch L, Stetler-Stevenson M (1998) Tissue inhibitor of metalloproteinase (TIMP)-1 induces differentiation and an antiapoptotic phenotype in germinal center B cells. Blood 92:1342–1349PubMed
29.
Zurück zum Zitat Guimaraes DA, Rizzi E, Ceron CS, Oliveira AM, Oliveira DM, Castro MM, Tirapelli CR, Gerlach RF, Tanus-Santos JE (2011) Doxycycline dose dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol 108:318–325CrossRefPubMed Guimaraes DA, Rizzi E, Ceron CS, Oliveira AM, Oliveira DM, Castro MM, Tirapelli CR, Gerlach RF, Tanus-Santos JE (2011) Doxycycline dose dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol 108:318–325CrossRefPubMed
30.
Zurück zum Zitat Nagase N (2001) Substrate specificity of MMPs. In: Clendeninn NJ, Krzysztof A (eds) Cancer drug discovery and development: matrix metalloproteinase inhibitors in cancer therapy. Humana Press Inc., Totowa Nagase N (2001) Substrate specificity of MMPs. In: Clendeninn NJ, Krzysztof A (eds) Cancer drug discovery and development: matrix metalloproteinase inhibitors in cancer therapy. Humana Press Inc., Totowa
Metadaten
Titel
Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair
verfasst von
Job C. Tharappel
Jennifer W. Harris
Brittany A. Zwischenberger
Salomon M. Levy
David A. Puleo
J. Scott Roth
Publikationsdatum
12.08.2015
Verlag
Springer US
Erschienen in
Surgical Endoscopy / Ausgabe 5/2016
Print ISSN: 0930-2794
Elektronische ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-015-4434-0

Weitere Artikel der Ausgabe 5/2016

Surgical Endoscopy 5/2016 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.