Microvascular no-reflow after endovascular therapy: The molecular ceiling on hemodynamic optimization and the next therapeutic frontier

Endovascular thrombectomy restores macrovascular patency but fails to achieve tissue-level perfusion in approximately 30% of cases, likely because of the no-reflow phenomenon. Even after optimized hemodynamic management, 40% of patients with angiographically successful recanalization fail to achieve functional independence, revealing a biological ceiling beyond blood pressure optimization. I propose that pericyte contraction via endothelin-1/ET-A receptor signaling, neutrophil CD11b/CD18-dependent capillary plugging, and platelet microthrombus, mechanisms operating orthogonally to systemic hemodynamics, define this ceiling. I review imaging and biomarker strategies for identifying microvascular failure and discuss endothelin receptor antagonism, integrin blockade, and intra-arterial thrombolysis as therapeutic priorities for next-generation of post-thrombectomy trials.