Assessment of cerebral autoregulation using continuous-wave near-infrared spectroscopy during squat-stand maneuvers in subjects with symptoms of orthostatic intolerance.

Orthostatic lightheadedness in healthy young adults often leads to syncope in severe cases. One suggested underlying mechanism of orthostatic lightheadedness is a drop in transient blood pressure (BP); however, a decrease in BP does not always lead to a drop in cerebral blood flow (CBF) due to cerebral autoregulation (CA). We present a direct assessment method of CA using a multichannel continuous-wave near-infrared spectroscopy (CW-NIRS) device that measures the temporal changes in oxy- and deoxy-hemoglobin concentrations in the prefrontal cortex. Twenty healthy young adults were recruited. During the experiment, continuous beat-to-beat BP and heart rate were simultaneously measured during repetitive squat-stand maneuvers. We introduce a new metric termed 'time-derivative hemodynamic model (DHbT)', which is the time-derivative of total-hemoglobin concentration change that reflects the changes of cerebral blood volume and CBF. Although the absolute levels and the variations of systolic and diastolic BPs and mean arterial pressure showed no significant difference between the two groups, the proposed model showed a distinct difference in slope variation and response time of DHbT between the subjects with frequent symptom of orthostatic intolerance and the healthy control subjects. Thus, these results clearly demonstrate the feasibility of using CW-NIRS devices as a CA performance assessment tool.

Regional specific adaptation of the endothelial glycocalyx dimension in tail-suspended rats.

Previous animal studies by using tail-suspended hindlimb-unloaded rat model have shown that simulated microgravity-induced vessel structural and functional remodeling may be anatomic region dependent. However, little care has been taken to assess the structural adaptation of the endothelial glycocalyx, the apical surface of the endothelium, the key mechanosensor mediating nitric oxide (NO) production, and the natural protective barrier of the vasculature. Therefore, the present study extended simulated microgravity-induced vessel remodeling to the endothelial glycocalyx level. The percents of bone mineral density (BMD) change from both control and tail-suspended (TS) rats were measured by micro-computed tomography (Micro-CT). Structural parameters such as the luminal diameter (D), the thickness of each layer, the ratio of intima to media (IMR), the cross-sectional areas of the intima (CSAI) and media (CSAM) of vessels from three different regions (the common carotid artery, abdominal aorta, and femoral artery) were assessed by hematoxylin and eosin staining. Dimensions of the glycocalyx above, below, and away from the endothelial cell nucleus were examined by fluorescein isothiocyanate-labeled wheat germ agglutinin (WGA-FITC) binding to the cryosection of vessels. Our results show that 3-week tail suspension of rats increases the thickness and CSA of the abdominal aortic endothelium by 23.7 and 21.1%, respectively, thickens the media layer of the common carotid artery by 34.0%, and increases the luminal diameter, the CSA of the intima and media of the femoral artery by 75.7, 93, and 61.2%, respectively. Correspondingly, the dimension of the glycocalyx away from the common carotid arterial and the abdominal aortic endothelial cell nucleus from tail-suspended rats shows a 1.66- and 1.64-fold increase respectively, while it shows a 0.79-fold reduction on the top of the femoral endothelial cells. These results suggest that simulated microgravity induces vascular endothelial glycocalyx remodeling in a regional-dependent manner. The perturbation of the endothelial glycocalyx at the lower body artery may be the first event of vascular remodeling initiating endothelial dysfunction, contributing to postspaceflight orthostatic intolerance.

Utility of corrected QT interval in orthostatic intolerance.

We performed this study to determine whether electrocardiographic corrected QT (QTc) interval predicts alterations in sympathovagal balance during orthostatic intolerance (OI). We reviewed 1,368 patients presenting with symptoms suggestive of OI who underwent electrocardiography and composite autonomic function tests (AFTs). Patients with a positive response to the head-up tilt test were classified into orthostatic hypotension (OH), neurocardiogenic syncope (NCS), or postural orthostatic tachycardia syndrome (POTS) groups. A total of 275 patients (159 OH, 54 NCS, and 62 POTS) were included in the final analysis. Between-group comparisons of OI symptom grade, QTc interval, QTc dispersion, and each AFT measure were performed. QTc interval and dispersion were correlated with AFT measures. OH Patients had the most severe OI symptom grade and NCS patients the mildest. Patients with OH showed the longest QTc interval (448.8±33.6 msec), QTc dispersion (59.5±30.3 msec) and the lowest values in heart rate response to deep breathing (HRDB) (10.3±6.0 beats/min) and Valsalva ratio (1.3±0.2). Patients with POTS showed the shortest QTc interval (421.7±28.6 msec), the highest HRDB values (24.5±9.2 beats/min), Valsalva ratio (1.8±0.3), and proximal and distal leg sweat volumes in the quantitative sudomotor axon reflex test. QTc interval correlated negatively with HRDB (r = -0.443, p<0.001) and Valsalva ratio (r = -0.425, p<0.001). We found negative correlations between QTc interval and AFT values representing cardiovagal function in patients with OI. Our findings suggest that prolonged QTc interval may be considered to be a biomarker for detecting alterations in sympathovagal balance, especially cardiovagal dysfunction in OH.

The effect of exercise training on left ventricular relaxation and diastolic suction at rest and during orthostatic stress after bed rest.

A marked reduction in upright stroke volume (SV) contributes substantially to orthostatic intolerance after exposure to spaceflight or bed rest. It is unclear whether slowed left ventricular (LV) relaxation and diastolic suction contribute to the reduction in SV or whether these changes are influenced by exercise training while in bed. Twenty-seven healthy adults completed 5 weeks of -6 deg head-down bed rest (HDBR). During HDBR, nine subjects were sedentary (NOEX), while 18 performed near-daily rowing ergometry (EX). Left ventricular mass, SV, LV end-diastolic volume (LVEDV), pulmonary capillary wedge pressure and Doppler ultrasound indices of LV function were collected pre- and post-HDBR during supine rest (twice) and during reduced LV loading (lower body negative pressure; LBNP) and increased LV loading (saline infusion). Post-HDBR, LV mass increased in the EX group, but decreased in the NOEX group. The reduction in SV and LVEDV during supine rest and LBNP were greater with NOEX in comparison to EX after HDBR. Peak early mitral annular velocity, isovolumic relaxation time, early propagation velocity, a non-invasive index of early diastolic filling and ventricular diastolic suction, and peak global longitudinal early strain rate were slowed during supine rest after HDBR with NOEX; however, these variables were either unaltered or the reduction was less prominent with EX. Doppler ultrasound measures of early diastolic filling, ventricular relaxation and diastolic suction were not significantly affected during LV unloading by LBNP after HDBR in either group. All Doppler indices were restored to pre-HDBR levels in both groups during saline infusion to normalize LV filling pressure after HDBR. It is concluded that Doppler indices of dynamic LV filling were reduced in both groups after HDBR; however, these effects were more pronounced in the NOEX group. Irrespective of group, post-HDBR Doppler parameters were restored when LV filling pressure was increased to pre-HDBR levels during saline infusion. Therefore, the reduction in upright SV after HDBR is more influenced by changes in LV loading conditions, namely left atrial pressure in the setting of LV remodelling, rather than ventricular relaxation and diastolic suction.

Blood flow in internal carotid and vertebral arteries during orthostatic stress.

It remains unclear whether orthostatic stress evokes regional differences in cerebral blood flow. The present study compared blood flow in the internal carotid (ICA) and vertebral arteries (VA) during orthostatic stress (60 deg head-up tilt; HUT) in six healthy young men. The ICA and VA blood flow were measured using Doppler ultrasonography. Dynamic cerebral autoregulation was also determined during supine (Supine) and HUT conditions, from the rate of regulation (RoR) in cerebrovascular conductance of the ICA and VA during acute hypotension induced by the release of bilateral thigh-cuffs. The HUT decreased ICA blood flow by -9.4 ± 1.7% (P < 0.01 versus Supine), leaving ICA conductance unchanged. In contrast, there was no significant difference in VA blood flow between Supine and HUT, and VA conductance increased (+12.9 ± 0.8%, P < 0.01). In addition, dynamic cerebral autoregulation in both the ICA and VA was attenuated during HUT, and the magnitude of the attenuation in RoR was greater in the VA [0.25 ± 0.03 s(-1) Supine versus 0.16 ± 0.02 s(-1) HUT (-33.9 ± 5.8%); P < 0.05] compared with the ICA [0.23 ± 0.02 s(-1) Supine versus 0.20 ± 0.03 s(-1) HUT (-10.6 ± 13.4%); P > 0.05]. These data indicate that orthostatic stress evokes regional differences in cerebral blood flow and possible differences in dynamic cerebral autoregulation between two main brain vascular areas in response to an acute change in blood pressure during orthostatic stress.

Artificial gravity with ergometric exercise can prevent enhancement of popliteal vein compliance due to 4-day head-down bed rest.

Changes of venous compliance may contribute in part to postflight orthostatic intolerance. The purpose of the present study was to determine whether intermittent artificial gravity exposure with ergometric exercise could prevent venous compliance changes in the lower limbs due to simulated weightlessness. Twelve healthy male volunteers were exposed to simulated microgravity for 4 days of head-down bed rest (HDBR). Six subjects were randomly loaded 1.0-2.0 Gz intermittent artificial gravity (at foot level) with 40 W of ergometric workload every day (countermeasure group, CM). The six others served as the control (CON group). Venous compliance was estimated by measuring the corresponding change of cross-sectional area (CSA) of popliteal vein at each minute of various venous occlusion pressure stages. Basal CSA was significantly lower after bed rest in the control group, and preserved in the countermeasure group. The percent increase in the CSA of CON group was significantly greater almost at each minute of various venous cuff pressures after bed rest than before. Compliance of popliteal vein of CON group was significant greater when 40, 60 and 80 mmHg cuff pressure applied after bed rest than before of CON group. In conclusions, a 4-day simulated weightlessness leads to increase of popliteal venous compliance; centrifuge-induced artificial gravity with ergometric exercise can prevent enhancement of popliteal venous compliance due to 4-day head-down tilt bed rest, the effect of the countermeasure on compliance might involve changes in venous filling and changes in venous structure.

Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest.

OBJECTIVE: Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR). METHOD: Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress. RESULTS AND DISCUSSION: Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest. CONCLUSION: The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope.

Role of sympathetic responses on the hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fractional, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT), termed the "push-pull effect." The aim of the present study was to test the hypothesis that sympathetic responses contribute to the push-pull effect. Young, healthy subjects (n = 7 males and 3 females) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced design, and 1 min was allowed for recovery between tilts. This protocol was repeated during clonidine administration (2.5 microg/kg bolus over 30 min and then continuously at 0.36 microg x kg(-1) x h(-1)). Clonidine blunted the vasomotor responses to tilting, and this led to exaggerated changes in arterial pressure. Clonidine exerted little specific influence on the push-pull effect. Thus sympathetic responses appear neither to contribute to, nor protect against, the push-pull effect for the rate and duration of tilting imposed in the present study.