Morphological and Haemodynamic Implications of Carotid Artery Endarterectomy vs. Stenting

Introduction: Spinal cord ischaemia (SCI) is a major complication in thoraco-abdominal aortic aneurysm surgery.The identification of neuroprotective substances to prevent this complication is of great interest.Tetrahydrobiopterin (BH4) is one of five essential cofactors of nitric oxide synthase (NOS).Ischaemia reperfusion injury is associated with intracellular BH4 depletion, caused by an uncoupling of NOS with increased production of surrounding radicals.Pre-treatment with BH4 plays a protective role in ischemia reperfusion injury and we therefore wanted to test the neuroprotective potential of this substance.Methods: SCI was induced in rats by balloon occlusion of the descending thoracic aorta.Animals were subdivided into a sham group (n ¼ 12), a treatment group (50 mg/kg BH4 intramuscular 15 minutes before SCI; n ¼ 11) and a control group (intramuscular saline injection 15 minutes before SCI; n ¼ 12).Blinded neurofunctional testing was performed using the Bassio-Beattie-Breshnahan (BBB) locomotor rating scale.Harvested spinal cords were further evaluated (H.E.staining and TUNEL assays).Results: The model was associated with an unexpectedly high perioperative mortality due to haemodynamic and embolic complications.Within the control group, three animals (n ¼ 12; 25%), within the treatment group four animals (n ¼ 11; 36%) survived until the defined study endpoint (day 7).Pre-treatment with BH4 led to a significantly better neurological outcome immediately after awakening the animals.The difference of BBB scores showed a trend towards a better outcome after pre-treatment with BH4 at day 7. Histopathological evaluation using H.E. staining to count the number of neurons revealed no difference between the treatment and control group.By using TUNEL assays for detection of vital neurons there was a clear trend towards a benefit of pre-treatment with BH4. Conclusion:The neuroprotective potential of BH4 as immediate post-operative neurological outcome was significantly better in pre-treated animals.Due to the unexpectedly high post-operative mortality, Results of neurofunctional and histopathological evaluations at day 7 should be taken with caution.However, the observed trend towards a benefit of BH4 pre-treatment urges to repeat the study with a shorter post-operative observation period.

Abstract licence: CC BY-NC-ND

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