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

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.