A stage of mechanisms of pathological cerebral blood flow reduction due to severe central hypovolemia: a study using maximal lower body negative pressure

We hypothesize that excessive central blood flow reduction leads to failure in the mechanism that appropriately distributes cerebral blood flow (CBF), preceding the pathological drop in blood pressure. This study aims to evaluate changes in CBF and cerebrovascular resistance in response to reduced cardiac output (CO) during severe central hypovolemia and elucidate the breakdown of cerebral circulation maintenance mechanisms before presyncope. Nine healthy men underwent maximal lower body negative pressure (LBNP), with ultrasound measurements of the internal carotid artery (ICA) and vertebral artery (VA) blood flow, and CO. Hemodynamic changes, including total peripheral resistance (TPR) and fractional CBF (CBF/CO), were assessed. CO decreased from LBNP25%, while ICA and VA blood flow were preserved up to LBNP50% but declined from LBNP75%. CBF/CO increased until LBNP75%, then plateaued or slightly decreased. TPR increased from LBNP50% to LBNP75%, then plateaued. Both ICA-CVRi and VA-CVRi increased with higher LBNP loads. ICA-CVRi showed significant elevations at LBNP75% and LBNPpremax, whereas VA-CVRi reached a significantly higher value at LBNPpremax. The decrease in ICA and VA blood flow was smaller than that in CO. The maintenance of blood flow at higher LBNP loads is likely due to peripheral vascular constriction, but this compensatory mechanism failed at LBNP75%, just before presyncope.<b>NEW & NOTEWORTHY</b> This study examined cerebral blood flow (CBF) responses to reduced cardiac output (CO) during severe central hypovolemia. The CBF/CO ratio increased but plateaued at 75% lower body negative pressure (LBNP). Decreases in internal carotid and vertebral artery blood flow were smaller than the CO reduction. CBF was maintained at high LBNP levels, likely via peripheral vasoconstriction. However, this compensatory mechanism failed at 75% LBNP, immediately before presyncope, indicating a breakdown in cerebral circulatory regulation.