International Journal of Colorectal Disease

, Volume 25, Issue 12, pp 1459–1464

Effect of beta blocker combined with COX-2 inhibitor on colonic anastomosis in rats

  • Barak Benjamin
  • Ofir Hazut
  • Lee Shaashua
  • Marganit Benish
  • Niv Zmora
  • Iris Barshack
  • Aviad Hoffman
  • Shamgar Ben-Eliyahu
  • Oded Zmora
Original Article

DOI: 10.1007/s00384-010-0992-8

Cite this article as:
Benjamin, B., Hazut, O., Shaashua, L. et al. Int J Colorectal Dis (2010) 25: 1459. doi:10.1007/s00384-010-0992-8

Abstract

Purpose

Pharmacologic modulation of the perioperative physiologic stress response, using the beta-blocker propranolol, combined with the COX-2 inhibitor etodolac, has been shown to reduce metastatic spread and increase survival rates following surgery for primary tumor excision in rodents. Prior to implantation of this pharmacological approach in clinical trials in patients with colon cancer, the safety of this technique has to be evaluated. This study assessed the effects of these drugs on the healing of colonic anastomosis in rats.

Methods

Forty-eight F344 rats were divided into two groups, which were given seven daily subcutaneous injections of either vehicle, or propranolol (up to 1.2 mg/kg/day) combined with etodolac (12.5 mg/kg/day), starting the day before surgery. Each animal underwent laparotomy, colotomy of the descending colon, and anastomosis. Anastomotic leak rate and bursting pressure were compared at 1 week after the operation. The harvested anastomosis was histologically assessed for wound healing parameters.

Results

Forty-three rats survived the operation and were eligible for analysis at 1 week. No significant difference in survival, anastomotic leakage, or bursting pressure was found between animals that received propranolol and etodolac versus those receiving vehicle (drugs 179 mmHg ± 45.4; vehicle 187 mmHg, SD ± 35.0, p = 0.54). Histologic assessment of fibrosis, necrosis, cell infiltration, and tissue reaction zone did not differ between the two groups.

Conclusions

Perioperative administration of propranolol and etodolac seems safe in colon operations in rats and does not affect anastomotic failure or colon healing.

Keywords

Propranolol Etodolac Colorectal neoplasms/prevention and control Anastomosis Surgical 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Barak Benjamin
    • 1
  • Ofir Hazut
    • 2
  • Lee Shaashua
    • 2
  • Marganit Benish
    • 2
  • Niv Zmora
    • 4
  • Iris Barshack
    • 3
  • Aviad Hoffman
    • 4
  • Shamgar Ben-Eliyahu
    • 2
  • Oded Zmora
    • 4
  1. 1.Department of SurgeryMeir Medical CenterTel AvivIsrael
  2. 2.Neuroimmunology Research Unit, Department of PsychologyTel Aviv UniversityTel AvivIsrael
  3. 3.Department of PathologySheba Medical CenterTel AvivIsrael
  4. 4.Department of Surgery and TransplantationSheba Medical CenterTel-HashomerIsrael

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