Preclinical animal model for evaluation of ischemia and reperfusion injury of the spinal cord after cross-clamping of the aorta

Spinal ischemia and the resulting reperfusion is a crucial problem in aortic cross-clamping. In pig models, such as the Ulm model, with sacrifice of the animal at the end of the experiment the neurological outcome cannot be determined. In New Zealand white rabbits spinal ischemia can be induced by cross-clamping of the infrarenal aorta due to segmental blood supply of the spinal cord. In preliminary trials a clamping time of 15 min was defined as being optimal. Functional neurologic outcome was assessed by using the modified Tarlov score. Animals were anesthetized by a mixture of ketamine (50mg/kg body weight) and xylazine (5mg/kg). Blood pressure, heart rate, oxygen saturation and temperature were monitored intraoperatively. Due to positive effects found in former investigations carbamylated erythropoietin (cEPO) was selected for the treatment group. Neurological examinations were undertaken after declamping and subsequently every 12 h. At 96 h the animals were sacrificed and the spinal cords were removed for histopathological examination. Overall 20 animals could be examined, 10 in the treatment group and 10 in the placebo group. After aortic cross-clamping all animals showed complete paraplegia (Tarlov score 0/5). Within the first 12-24 h animals showed an incomplete neurological recovery (Tarlov score 4.25/5) while a decline in hind limb motion was observed in the following days (Tarlov score 3.55/5). Histopathological examination did not reveal any injury in thoracic sections of the spinal cord whereas damage in lumbal sections correlated significantly with neurological symptoms (p=0.007). The treatment group (cEPO) and the placebo group showed no differences in neurological or histopathological outcome. This is a highly reproducible model which allows clinical neurological assessment after aortic cross-clamping. Using this model promising pharmaceutics influencing ischemia tolerance can be tested clinically and histopathologically. In the initial experimental series with a cross-clamping time of 15 min no significant improvement of the clinical or histological damage could be achieved by administration of cEPO.