Abolition of anti-adhesiogenic effect of heparin by protamine sulfate

Abstract

Objective: Intraabdominal adhesion is a frequently encountered condition after surgery and can end up in important complications. The objective of this study is to test whether the antiadhesiogenic effect of heparin could be antagonized by administration of protamine in a rat model.

Material and methods: A laparotomy with caecal abrasion model was used in 40 Wistar rats. Single dose of 1 cc saline was injected subcutaneously (SC) in one group (control); 50 IU/kg heparin was injected SC in Group 2; 50 IU/kg protamine SC given to Group 3; 50 IU/kg heparin and 50 IU/kg protamine was given SC to Group 4 for 3 consecutive days. Each group consisted of 10 rats. All rats were sacrificed one week later for macroscopic and microscopic examination and they were scored for adhesion using Mazuji adhesion scale.

Results: There was significant difference in the heparin group with respect to Mazuji adhesion score, histopathological score (fibrosis, inflammation and vascular proliferation) and S-100 staining (P < 0.05). Additionally, the inflammation was more severe in the mucosa and submucosa compared to serosa in the heparin group (P < 0.01). With respect to fibrosis and vascular proliferation, apart from submucosal fibrosis, heparin group was statistically superior to the control group by means of each layer (P < 0.01).

Conclusion: It seems that heparin is effective preventing adhesion in this rat model. Abolition of heparin's antiadhesiogenic effect by protamine administration is likely exerted via its antithrombine activity. Clinical application of our findings in intraabdominal surgery warrants further investigation.

Keywords: Adhesion; Anticoagulant; Antidote; Antithrombine; Protamine sulfate.