Abstract WP377: Metabolomic Profiling of Distal Blood during Thrombectomy Identifies 2,3-bisphosphoglycerate as a Biomarker of Ischemic Metabolism

Background: Although successful recanalization improves outcomes after mechanical thrombectomy for acute ischemic stroke, reliable prognostic markers beyond revascularization are lacking. Distal-to-occlusion blood may directly reflect the ischemic microenvironment, but its metabolic characteristics remain largely unexplored. Methods: Distal blood was obtained via microcatheter during thrombectomy for acute ischemic stroke (n=8) and during carotid artery stenting (n=4 controls). Targeted metabolomics was performed by liquid chromatography–mass spectrometry (LC–MS). Parallel sampling was conducted in a rat permanent middle cerebral artery occlusion (MCAO) model, with LC-MS analysis of ischemic brain tissue. In addition, a 4-vessel occlusion (4-VO) rat model was used to collect distal-to-occlusion blood, which was analyzed by Enzyme-linked immuno-sorbent assay (ELISA). Results: Principal component analysis (PCA) showed clear separation of ischemic distal samples from controls. 2,3-bisphosphoglycerate (2,3-BPG) levels were significantly elevated in thrombectomy patients’ distal blood (p<0.01, Figure. 1), in ischemic brain tissue from MCAO rats, and in distal blood collected from the 4-VO model. Conclusions: In conclusion, distal-to-occlusion blood exhibits a distinctive metabolic profile characterized by elevated 2,3-BPG. As an erythrocyte-derived metabolite that decreases hemoglobin oxygen affinity, 2,3-BPG promotes oxygen delivery to peripheral tissues and typically rises under hypoxic conditions. Our findings suggest that distal blood sensitively reflects the local oxygen–metabolic environment, and that elevated 2,3-BPG represents a metabolic adaptation to sustained ischemia (Figure. 2). This metabolite may serve as a biomarker of local ischemic adaptation and a potential predictor of long-term outcome after thrombectomy.