Abstract A084: Ischemic Postconditioning Reduces Infarct Growth and Modulates Immunothrombosis in Acute Stroke (INSPIRE): A Pilot Randomised Controlled Trial

Introduction: Ischemic postconditioning (IPostC) confers cytoprotection in preclinical stroke models. Nevertheless, its cytoprotective effect and mechanisms in humans remain uncertain. Methods: In this single-center, prospective, randomized, blinded-endpoint trial, we enrolled acute ischemic stroke patients who achieved successful endovascular thrombectomy (EVT) and assigned them to IPostC group (four cycles of 2-minute balloon inflation followed by 2-minute deflation) or control group. The primary outcome was infarct volume growth from baseline to the final infarct volume at 48 hours post-randomization. Secondary outcomes included final infarct volume, infarct volume within 2 hours, infarct growth from baseline to 2 hours, serial NIHSS scores during hospitalization, and 90-day mRS. Exploratory outcomes comprised indices of neutrophil and platelet activation (including platelet–neutrophil aggregates) and thromboelastography parameters; microcirculation time; and blood–brain barrier integrity. Untargeted plasma proteomics and metabolomics were performed to probe pathways modulated by IPostC. Results: IPostC reduced infarct volume growth versus control between baseline and 48 hours (mean difference log-transformed vs control, −51.3%; 95% CI, −72.8% to -12.9%), and between baseline and 2 hours (mean difference log-transformed vs control, −52.3%; 95% CI, −73.2% to -15.1%). NIHSS at 24 hours was significantly lower with IPostC than with control (mean difference log-transformed vs control, -21.3%; 95% CI, -36.6% to -2.4%). Mechanistically, IPostC decreased neutrophil CD11b expression (MFI: 5506±2271 vs 7154±3570 in controls; P=0.037) and platelet–neutrophil aggregates (16.71±9.50% vs 23.19±12.40%; P=0.027) and shortened microcirculation time (2.44±1.01s vs 30.8±1.01s; P=0.022). In addition, the peri-infarct Ktrans value was preserved with IPostC (1.15±0.54 vs 1.93±0.33; P