Venular-centered thrombo-inflammation drives microvascular failure after arterial recanalization in acute mesenteric ischemia: a translational study

ABSTRACT Acute mesenteric ischemia (AMI) remains associated with high mortality despite prompt revascularization, suggesting that downstream ischemia–reperfusion injury contributes to poor outcomes. However, the microvascular mechanisms underlying this process remain poorly defined. We analyzed admission blood samples from patients with arterial AMI and non-ischemic controls and investigated thrombo-inflammatory responses in a murine superior mesenteric artery occlusion (SMAO) model. In mice, intravital microscopy was used to directly visualize mesenteric microcirculatory flow and thrombo-inflammatory events during ischemia–reperfusion. Patients with AMI displayed a marked systemic thrombo-inflammatory profile, characterized by elevated inflammatory markers, neutrophil activation, platelet activation, and alterations in coagulation-related proteins, which were closely mirrored in the SMAO model. Intravital microscopy revealed a dissociation between arterial and microvascular reperfusion: while arteriolar flow partially recovered after recanalization, venular perfusion remained severely impaired and was associated with early blood cell stasis and stable venular thrombus formation. Thrombi developed through a sequential process initiated during ischemia and amplified during reperfusion. Together, these findings identify venular-centered thrombo-inflammation as a key determinant of microvascular dysfunction and intestinal injury in arterial AMI, and provide a mechanistic framework for targeting thrombo-inflammatory pathways beyond arterial reperfusion that may extend to other clinical forms of AMI, including non-occlusive mesenteric ischemia (NOMI).