Secondary venous ischemic injury ameliorations through medical treatment in rats

Abstract

Background: Secondary venous ischemia caused by anastomotic failure is one of the major reasons for the lack of success in free flap surgeries. Development of damage can be mediated with single or multiple drugs. This study examined the effects of allopurinol, cyclosporine A, and deferoxamine as monotherapies and combination therapies on inguinal island flap in rats. Material and Methods: 54 rats were divided into the following nine groups containing six animals each as controls, monotherapies, and combination therapies. Intravenous cyclosporine A (30 mg/kg), allopurinol (100 mg/kg), and deferoxamine (150 mg/kg) were administered after secondary venous ischemia. One hour after termination of the secondary venous ischemia, a biopsy was removed for biochemical (levels of malondialdehyde, the last product of lipid peroxidation; myeloperoxidase, the indicator of neutrophil infiltration; and glutathione, a potent cellular antioxidant) and histopathological (neutrophil count, an indicator of tissue inflammation) assessment. Flap viability was examined on the seventh day following surgery. Results: The treatment groups had greater flap viability and glutathione levels, and lower levels of malondialdehyde, myeloperoxidase, and neutrophil count. The differences between the control, monotherapy and combination therapy groups were significant (p < 0.05). Conclusions: The beneficial effect of allopurinol, previously demonstrated in primary ischemia models and arterial ischemia models, was also seen in the secondary venous ischemia model. Dual and triple combinations were more effective than monotherapies in terms of the viability of the flap. These results supported our hypothesis that combination therapies with these agents progressively decrease ischemic damage.