Sildenafil in the treatment of fat embolism: a rat model

Abstract

ABSTRACT

Background: Sudden, peri-operative cardiovascular deterioration with decreased systemic arterial pressure and increased pulmonary arterial pressure is a potentially fatal complication of orthopaedic surgery, due to fat embolism. In this situation pulmonary vasodilation is an attractive treatment option and this was studied using the drug sildenafil.

Methods: Bone cement (polymethylmethacrylate) was injected into bilateral femora in 12 male Sprague-Dawley rats. Systemic blood pressure, pulmonary arterial pressures and EEG (electro-encephalogram) were recorded till 60 minutes after the orthopaedic procedure. Twenty minutes before cement injection, 6 animals received 5 mg/kg of sildenafil which was injected through the intraperitoneal route and 6 received saline delivered similarly. After euthanasia, the lungs were used for imaging studies with micro-CT (micro-computed tomography). Post-mortem lung and brain biopsies were taken for semi-quantitative analysis of intravascular fat.

Results: Fat embolism was associated with an increase in pulmonary arterial blood pressure. In the sildenafil group pulmonary arterial pressures remained below baseline values except for a transient period of few seconds following cement pressurisation. There was statistically significant decrease in mean pulmonary arterial pressure (p=0.037) after administration of sildenafil and after injection of cement (p=0.025) in the experimental group as opposed to control. There was no significant difference in the number of fat emboli in the lungs of both groups. There was a statistically significant significant increased lung perfusion in the sildenafil group as measured by micro-CT (micro-computed tomography) (p=0.0425). The EEG was not different between the 2 groups.

Conclusions: Administration of sildenafil appeared to ameliorate the acute cardiovascular complications of fat embolism in the rat model.