Procedure-related vasospasm and reperfusion vulnerability during mechanical thrombectomy

Mechanical thrombectomy (MT) has reshaped the treatment of acute ischemic stroke caused by large-vessel occlusion (LVO), yet successful angiographic reperfusion does not reliably translate into meaningful neurological recovery. Landmark randomized trials and the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) patient-level meta-analysis established MT as standard of care, but they also brought into focus the persistent problem of incomplete tissue-level rescue despite technically successful recanalization. Procedure-related vasospasm is usually handled as a transient intraprocedural complication, commonly with intra-arterial calcium-channel blockers, and is rarely considered within the broader biology of reperfusion failure. In this mini-review, we propose that vasospasm during endovascular thrombectomy (EVT) should be reinterpreted as a visible marker of a more complex reperfusion-failure state. This state may encompass endothelial injury, distal embolization, inflammatory leukocyte-endothelial interactions,platelet-rich microthrombi, pericyte-mediated capillary constriction, and microvascular no-reflow. Within this framework, intra-arterial vasodilators warrant renewed attention not only for their ability to restore conduit vessel diameter, but also for their potential to influence the quality of tissue perfusion. This perspective is particularly relevant for phosphodiesterase-3 (PDE3) inhibitors such as milrinone, whose pharmacological profile combines vasodilatory effects with biologically demonstrable modulation of platelet activity. Beyond conduit vessel relaxation, such agents may act at the interface between macrovascular recanalization and microvascular reperfusion. We propose that procedure-related vasospasm may identify a subgroup of patients in whom successful recanalization fails to secure effective microvascular reperfusion, and that future studies should evaluate vasodilator strategies using endpoints that extend beyond angiographic resolution to include tissue perfusion, infarct evolution, and functional outcome.