Background and Aims: Decreased cerebrovascular reactivity (CVR) in patients with significant internal carotid artery stenosis (ICAS ≥ 70%) is an independent risk factor for cerebral infarction. To evaluate CVR, changes in cerebral perfusion pressure and blood flow velocity (BFV) of the middle cerebral artery (MCA) can be estimated by CO₂- (hyperventilation—HV and breath-holding—BH) and pressure–flow-based (Common Carotid Artery Compression—CCC and Valsalva Maneuver—VM) stimuli. We used a multimodal approach to characterize CVR in patients before carotid endarterectomy (CEA). Methods: HV, BH, CCC, and VM tests were performed on 31, 26, and 34 patients. BFV of MCAs was monitored by transcranial Doppler, and continuous arterial blood pressure was registered non-invasively. CVR was compared between the operated significantly stenotic and the contralateral sides. Results: The extent of HV- and BH-induced CVR was similar, but the time to the lowest HV-induced BFV was shorter on the side with significant ICAS. The response to CCC was sensitive to hemodynamic asymmetry in the transient hyperemic response ratio and in the cumulative change in the (mean arterial blood pressure)/(mean BFV) ratio. In VM, the slope of BFV increased in the ascending (2b) phase, and the time to overshoot correlated with the side of the stenosis. Conclusions: These results suggest that in patients with significant ICAS, in addition to CO₂ reactivity measurements, a more complex estimation of CVR, by using hemodynamic tests (CCC and VM), should also be used to better quantify cerebral ischemic risk.

Post-cardiac arrest brain injury is driven by both global cerebral hypoperfusion and subsequent reperfusion. However, hyperacute blood-based neurobiomarker kinetics after precisely defined (very) low-flow intervals remain poorly characterized. During transcatheter aortic valve implantation (TAVI), rapid ventricular pacing (RVP) induces a transient pulseless ventricular tachycardia, functionally mimicking brief cardiac arrest. In this single-centre, prospective, self-controlled cohort study, adults undergoing TAVI were enrolled. RVP (120-200 bpm) was applied to transiently suppress forward flow. Invasive aortic pressure, common carotid- (CCA) and middle cerebral artery (MCA) flow were recorded continuously. Serum samples were obtained pre-procedure and 20, 65, 110 and 200 minutes after RVP. Neuron specific enolase (NSE), and S100 were measured as neurobiomarkers. In case of the 76 enrolled patients, median cumulative RVP duration was 60 s (IQR 41-92). During RVP, MCA and CCA flow showed a very low-flow state while aortic pressure fell below the presumed autoregulatory threshold. NSE concentrations increased progressively from baseline to 200 minutes (T0: 10.6 [9.1-13.0]; T20: 12.8 [11.6-15.5]; T65: 15.1 [13.0-18.6]; T110: 15.8 [13.8-18.6]; T200: 17.0 [14.2-20.5] µg/L). S100B concentrations showed an inverse U-shaped profile (T0: 0.05 [0.04-0.07]; T20: 0.13 [0.10-0.18]; T65: 0.14 [0.11-0.23]; T110: 0.11 [0.08-0.16]; T200: 0.08 [0.06-0.12] µg/L). No patient developed neurological deficits. Controlled (very) low-flow episodes during TAVI induce measurable, but clinically silent, elevations of NSE and S100. Neurobiomarkers reflects with distinct kinetics on ischaemia and reperfusion following a short, very low-flow cardiac arrest.

Background: In patients with severe atherosclerotic internal carotid artery stenosis (ICAS), the capacity of cerebral vasoreactivity (CVR)—an independent risk factor for cerebral ischemia—is reduced, and dysregulation of arterial blood pressure (ABP) may also be present. Thus, this study assessed the relationship between changes in cerebral blood flow velocity (BFV) in response to vasoactive stimuli (as measured by transcranial Doppler (TCD)), characterizing CVR and cardiovascular autonomic nervous system (CANS) function. Methods: Common carotid artery compression (CCC n = 26), hyperventilation (HV) and breath-holding (BH) tests (n = 31), and the Valsalva maneuver (VM n = 34) were used to assess CVR in patients with ICAS. In the middle cerebral arteries, BFV was monitored by TCD, whereas ABP was registered non-invasively. For statistical analysis, validated indices describing CANS function—namely, sympathetic index (SI), pressure recovery time (PRT), and Valsalva heart rate ratio (VHRR)—were selected based on the VM response. Several parameters were defined in order to evaluate CVR responses, including cerebral arterial resistance (CAR = ABP/BFV), which was correlated with the CVR indices using Spearman’s pairwise correlation and canonical correlation. Results: A significant correlation was found between several CVR indices of the HV-BH and VM tests and CANS indices of VM using Spearman’s pairwise correlation test. Regarding the HV-BH CVR and CANS indices of VM, a significant correlation was found between CAR values until it reached its maximum on the to-be-operated side (CAR_{timetomaxICAop}) and VHRR (p = 0.041). A significant correlation was also found between the time elapsed until the CAR minimum value (CAR_{timetominICAop}) and SI (p = 0.019). Concerning the CVR and CANS indices of the VM, a significant correlation was found between cerebrovascular Valsalva ratio on the to-be-operated side (CVAR_ICAop) and PRT (p = 0.002). Canonical correlation analysis confirmed that impairments of CANS and CVR may be associated. Conclusions: In patients with severe ICAS, the potentially concomitant dysregulation of cerebrovascular reactivity and the cardiovascular autonomic nervous system can further increase cerebral ischemic risk.