Trapezoidal Wave Chest Compression Improves Blood–Brain Barrier After Cardiac Arrest via Downregulating Integrin β3 in Brain Microvascular Endothelial Cells

ABSTRACT Disruption of the blood–brain barrier (BBB) is a critical mechanism of global cerebral ischemic injury and neurological deficits under cardiac arrest (CA). Compared to traditional sinusoidal wave chest compression (SW‐CPR), the trapezoidal wave chest compression (TW‐CPR) technique has been shown to improve blood flow and increase microcirculation during CPR. However, the effect of TW‐CPR on BBB and the underlying molecular mechanism remains to be illustrated. In this study, TW‐CPR and SW‐CPR were respectively used on rats following CA. After resuscitation, the cerebral cortical perfusion, BBB integrity, and neurological outcomes were assessed. RT‐qPCR, immunofluorescence staining, and Western blot analyses were employed to measure the expression of mechanotransducer proteins. The integrin β3 inhibitor (cRGDfk) and adeno‐associated virus‐ITGB3 shRNA were administered, and protein expression was assessed by Western blot, including the expression of downstream signals of differentially expressed proteins. We found that rats receiving TW‐CPR showed significantly higher survival rates (73.3% vs. 53.3%, p = 0.014) and improved neurological function scores compared to SW‐CPR ( p = 0.020). TW‐CPR also reduced BBB disruption, as evidenced by decreased Evans blue dye extravasation and elevated levels of tight junction proteins occludin and claudin‐5. Hemodynamic measurements indicated that TW‐CPR enhanced peripheral circulation, as shown by increased arterial pressure and left common carotid artery blood flow velocity. Additionally, cerebral cortical microcirculation was better preserved in the TW‐CPR group, with higher perfused vessel density (PVD) and microvascular flow index (MFI) compared to SW‐CPR. TW‐CPR was also associated with reduced integrin β3 expression in BMECs, which may contribute to its protective effects on the BBB. In conclusion, TW‐CPR can improve cerebral microcirculation, thus attenuating BBB injury via inhibiting integrin β3 in BMECs after CA/CPR in rats.