Microvascular Occlusion and Postrecanalization Hyperperfusion in a Swine Model of Acute Ischemic Stroke

Despite successful recanalization after endovascular thrombectomy, more than half of patients with acute ischemic stroke with large-vessel occlusions experience an unsatisfactory outcome. Incomplete microvascular reperfusion may contribute to it, but its occurrence remains debated, partly due to clinical observations of hyperperfusion after recanalization. This study investigates the relationship between ischemia duration, infarct development, microclot presence, and cerebral perfusion in a swine model of focal cerebral ischemia and reperfusion.

Twenty-three swine underwent craniectomy and were randomized into 5 groups: 1-hour, 2-hour, or 4-hour occlusion followed by 4-hour recanalization, 8-hour occlusion without recanalization (positive control), or without occlusion (sham). Middle cerebral artery occlusion was induced using aneurysm clips, with 3-dimensional digital subtraction angiography confirming occlusion and recanalization. Three-dimensional digital subtraction angiography was used for quantification of area at risk and tissue perfusion. Infarct size was measured using 2,3,5-triphenyl-2H-tetrazolium chloride staining. The presence of microclots was quantified using CD61+ platelet immunostaining (number/mm²). Plasma markers of coagulation activation were measured before and during middle cerebral artery occlusion and after recanalization.

Area at risk-normalized infarct size increased significantly with ischemia duration (r=0.8, P<0.001). Compared with the noninfarcted hemisphere, microclots in the infarcted hemisphere increased in middle cerebral artery occlusion groups (0.07 [0.04-0.13] versus 0.33 [0.16-0.71], P=0.003). Microclot density in area at risk region showed a positive correlation with ischemia duration (r=0.7, P=0.007), while no such correlation was observed in remote region. Simultaneously, higher perfusion levels were observed at both 2 hours (1.27±0.19, P<0.001) and 4 hours (1.23±0.16, P<0.001) following recanalization, irrespective of the duration of ischemia. No activation of coagulation was detected in systemic plasma.

Focal cerebral ischemia and reperfusion result in a substantial presence of microclots, which occurs alongside hyperperfusion in this swine model of recanalized acute ischemic stroke. These platelet microclots extend beyond the ischemic area. The density of microclots within the ischemic region increased with prolonged ischemia.