Job C Tharappel1, Jennifer W Harris1, Brittany A Zwischenberger1, Salomon M Levy1, David A Puleo2, J Scott Roth3. 1. Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA. 2. Department of Biomedical Engineering, University of Kentucky College of Medicine, Lexington, KY, USA. 3. Division of General Surgery, Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, UKMC C-222, Lexington, KY, 40536-0298, USA. jsroth2@uky.edu.
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.
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 rathernia 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.
Authors: Job C Tharappel; Curtis E Bower; Jennifer Whittington Harris; Sandeep K Ramineni; David A Puleo; J Scott Roth Journal: J Surg Res Date: 2014-05-10 Impact factor: 2.192
Authors: J R Salameh; Ladawn M Talbott; Warren May; Bashar Gosheh; Parminder J S Vig; D Olga McDaniel Journal: Am Surg Date: 2007-06 Impact factor: 0.688
Authors: Job C Tharappel; Jennifer W Harris; Crystal Totten; Brittany A Zwischenberger; John S Roth Journal: Surg Endosc Date: 2016-08-12 Impact factor: 4.584
Authors: Fellipe A T de Figueiredo; Roberta C Shimano; Edilson Ervolino; Dimitrius L Pitol; Raquel F Gerlach; Joao Paulo M Issa Journal: Sci Rep Date: 2019-10-25 Impact factor: 4.379