Effect of Fast Ascent, Acclimatization and Re-Exposure To 5050 m On Cerebral Autoregulation in Unacclimatized Lowlanders. A Prospective Cohort Study.

ABSTRACT Cerebral autoregulation (CA) is impaired during acute high-altitude (HA) exposure and effects of acclimatization and re-exposure on CA are unknown. In 18 healthy lowlanders (11 women), we hypothesized that the cerebral autoregulation index (ARI) assessed by the percentage change in middle cerebral artery peak blood flow velocity (Δ%MCAv)/percentage change in mean arterial blood pressure (Δ%MAP) induced by a sit-to-stand maneuver, is i) reduced on Day1 at 5050m compared to 520m, ii) is improved after 6 days at 5050m, and iii) is less impaired during re-exposure to 5050m after 7 days at 520m compared to Cycle1. Participants spent 4-8h/day at 5050m and slept at 2900m similar to real-life working shifts. High/low ARI indicate impaired/intact CA, respectively. With the sit-to-stand at 520m, mean(95%CI) in ΔMAP and ΔMCAv were -26%(-41 to -10) and -13%(-19 to -7); mean±SE in ARI was 0.58±0.63Δ%/Δ%, respectively. On Day1 at 5050m, ARI worsened compared to 520m (3.29±0.70Δ%/Δ%), but improved with acclimatization (1.44±0.65Δ%/Δ%, P<0.05 for both). ARI was less affected during re-exposure to 5050m (1.22±0.70Δ%/Δ%, P<0.05 acute altitude-induced change between sojourns). This study showed that CA i) is impaired during acute HA exposure, ii) improves with acclimatization and iii) is ameliorated during re-exposure to HA a week later.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Determinants of cerebral blood flow velocity change during squat-stand maneuvers

The large changes in mean arterial blood pressure (MABP) and cerebral blood flow velocity (CBFV) induced by squat-stand maneuvers (SSM) make this approach particularly suited for studying dynamic cerebral autoregulation (CA). However, the role of other systemic determinants of CBFV has not been described and could provide alternative physiological interpretations of SSM results. In 32 healthy subjects (16 female), continuous recordings of MABP (Finometer), bilateral CBFV (transcranial Doppler, MCA), end-tidal CO2 (EtCO2; capnography), and heart rate (HR; electrocardiogram) were performed for 5 min standing at rest, and during 15 SSM at the frequency of 0.05 Hz. A time-domain, multivariate dynamic model estimated the CBFV variance explained by different inputs, corresponding to significant contributions from MABP ( P < 0.00001), EtCO2 ( P < 0.0001), and HR ( P = 0.041). The autoregulation index (ARI; range 0–9) was estimated from the CBFV response to a step change in MABP. At rest, ARI values (typically 5.7) were independent of the number of model inputs, but during SSM, ARI was reduced compared with baseline ( P < 0.0001), and the three input model yielded lower values for the right and left MCA (3.4 ± 1.2, 3.1 ± 1.3) when compared with the single-input MABP–CBFV model (4.1 ± 1.1, 3.9 ± 1.0; P < 0.0001). The high coherence of the MABP–CBFV transfer function at 0.05 Hz (typically 0.98) was considerably reduced (around 0.71–0.73; P < 0.0001) when the contribution of CBFV covariates was taken into account. Not taking into consideration other determinants of CBFV, in addition to MABP, could be misleading and introduce biases in physiological and clinical studies.

Intra-aortic balloon pump does not influence cerebral hemodynamics and neurological outcomes in high-risk cardiac patients undergoing cardiac surgery: an analysis of the IABCS trial

Background The intra-aortic balloon pump (IABP) is often used in high-risk patients undergoing cardiac surgery to improve coronary perfusion and decrease afterload. The effects of the IABP on cerebral hemodynamics are unknown. We therefore assessed the effect of the IABP on cerebral hemodynamics and on neurological complications in patients undergoing cardiac surgery who were randomized to receive or not receive preoperative IABP in the ‘Intra-aortic Balloon Counterpulsation in Patients Undergoing Cardiac Surgery’ (IABCS) trial. Methods This is a prospectively planned analysis of the previously published IABCS trial. Patients undergoing elective coronary artery bypass surgery with ventricular ejection fraction ≤ 40% or EuroSCORE ≥ 6 received preoperative IABP (n = 90) or no IABP (n = 91). Cerebral blood flow velocity (CBFV) of the middle cerebral artery through transcranial Doppler and blood pressure through Finometer or intra-arterial line were recorded preoperatively (T1) and 24 h (T2) and 7 days after surgery (T3) in patients with preoperative IABP (n = 34) and without IABP (n = 33). Cerebral autoregulation was assessed by the autoregulation index that was estimated from the CBFV response to a step change in blood pressure derived by transfer function analysis. Delirium, stroke and cognitive decline 6 months after surgery were recorded. Results There were no differences between the IABP and control patients in the autoregulation index (T1: 5.5 ± 1.9 vs. 5.7 ± 1.7; T2: 4.0 ± 1.9 vs. 4.1 ± 1.6; T3: 5.7 ± 2.0 vs. 5.7 ± 1.6, p = 0.97) or CBFV (T1: 57.3 ± 19.4 vs. 59.3 ± 11.8; T2: 74.0 ± 21.6 vs. 74.7 ± 17.5; T3: 71.1 ± 21.3 vs. 68.1 ± 15.1 cm/s; p = 0.952) at all time points. Groups were not different regarding postoperative rates of delirium (26.5% vs. 24.2%, p = 0.83), stroke (3.0% vs. 2.9%, p = 1.00) or cognitive decline through analysis of the Mini-Mental State Examination (16.7% vs. 40.7%; p = 0.07) and Montreal Cognitive Assessment (79.16% vs. 81.5%; p = 1.00). Conclusions The preoperative use of the IABP in high-risk patients undergoing cardiac surgery did not affect cerebral hemodynamics and was not associated with a higher incidence of neurological complications. Trial registrationhttp://www.clinicaltrials.gov (NCT02143544).

Assessment of cerebral autoregulation in stroke: A systematic review and meta-analysis of studies at rest

Dynamic cerebral autoregulation (dCA) has been shown to be impaired in cerebrovascular diseases, but there is a lack of consistency across different studies and the different metrics that have been proposed for assessment. We performed a systematic review and meta-analyses involving assessment of dCA in ischemic and hemorrhagic stroke. Thirty-three articles describing assessment of dCA with transfer function analysis (TFA) were included, with meta-analyses performed for derived parameters of gain, phase and autoregulation index (ARI). A total of 1233 patients were pooled from 12 studies on acute ischemic stroke (AIS) and two studies on intracerebral hemorrhage (ICH). In comparison with controls, TFA phase of AIS was significantly reduced (nine studies), in both hemispheres ( P < 0.0001). TFA gain provided inconsistent results, with reduced values in relation to controls, for both hemispheres. The ARI (six studies) was reduced compared to controls, in both hemispheres ( P < 0.005). In ICH, gain showed higher values compared to controls for the unaffected ( P = 0.01), but not for the affected hemisphere. Meta-analyses in AIS have demonstrated that phase and the ARI index can show highly significant differences in comparison with healthy controls, while ICH have been limited by the scarcity of studies and the diversity of units adopted for gain.

Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip in patients with heart failure

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

Dynamic cerebral autoregulation following acute ischaemic stroke: Comparison of transcranial Doppler and magnetic resonance imaging techniques

Novel MRI-based dynamic cerebral autoregulation (dCA) assessment enables the estimation of both global and spatially discriminated autoregulation index values. Before exploring this technique for the evaluation of focal dCA in acute ischaemic stroke (AIS) patients, it is necessary to compare global dCA estimates made using both TCD and MRI. Both techniques were used to study 11 AIS patients within 48 h of symptom onset, and nine healthy controls. dCA was assessed by the rate of return of CBFV ( Rturn) following a sudden drop induced by the thigh cuff manoeuvre. No significant between-hemisphere differences were seen in controls using either the TCD or MRI technique. Inter-hemisphere averaged Rturn values were not different between TCD (1.89 ± 0.67%/s) and MRI (2.07 ± 0.60%/s) either. In patients, there were no differences between the affected and unaffected hemispheres whether assessed by TCD ( Rturn 0.67 ± 0.72 vs. 0.98 ± 1.09%/s) or MRI (0.55 ± 1.51 vs. 1.63 ± 0.63%/s). Rturn for both TCD and MRI was impaired in AIS patients compared to controls in both unaffected and affected hemispheres (ANOVA, p = 0.00005). These findings pave the way for wider use of MRI for dCA assessment in health and disease.