Kathryn Zuj

Cerebrovascular autoregulation: lessons learned from spaceflight research.

This review summarizes our current understanding of cerebral blood flow regulation with exposure to microgravity, outlines potential mechanisms associated with post-flight orthostatic intolerance, and proposes future directions for research and linkages with cerebrovascular disorders found in the general population. It encompasses research from cellular mechanisms (e.g. hind limb suspension: tissue, animal studies) to whole body analysis with respect to understanding human responses using space analogue studies (bed rest, parabolic flight) as well as data collected before, during, and after spaceflight. Recent evidence indicates that cerebrovascular autoregulation may be impaired in some astronauts leading to increased susceptibility to syncope upon return to a gravitational environment. The proposed review not only provides insights into the mechanisms of post-flight orthostatic intolerance, but also increases our understanding of the mechanisms associated with pathophysiological conditions (e.g. unexplained syncope) with clinical applications in relation to postural hypotension or intradialytic hypotension.

Cerebral critical closing pressure and CO2 responses during the progression toward syncope

Syncope from sustained orthostasis results from cerebral hypoperfusion associated with reductions in arterial pressure at the level of the brain (BPMCA) and reductions in arterial CO2 as reflected by end-tidal values (PetCO2). It was hypothesized that reductions in PetCO2 increase cerebrovascular tone before a drop in BPMCA that ultimately leads to syncope. Twelve men (21-42 yr of age) completed an orthostatic tolerance test consisting of head-up tilt and progressive lower body negative pressure to presyncope, before and after completing 5 days of continuous head-down bed rest (HDBR). Cerebral blood velocity (CBFV), BPMCA, and PetCO2 were continuously recorded throughout the test. Cerebrovascular indicators, cerebrovascular resistance, critical closing pressure (CrCP), and resistance area product (RAP), were calculated. Comparing from supine baseline to 6-10 min after the start of tilt, there were reductions in CBFV, PetCO2, BPMCA, and CrCP, an increase in RAP, and no change in cerebrovascular resistance index. Over the final 15 min before syncope in the pre-HDBR tests, CBFV and CrCP were significantly related to changes in PetCO2 (r = 0.69 ± 0.17 and r = 0.63 ± 0.20, respectively), and BPMCA, which was not reduced until the last minute of the test, was correlated with a reduction in RAP (r = 0.91 ± 0.09). Post-HDBR, tilt tolerance was markedly reduced, and changes in CBFV were dominated by a greater reduction in BPMCA with no relationships to PetCO2. Therefore, pre-HDBR, changes in PetCO2 with orthostasis contributed to increases in cerebrovascular tone and reductions in CBFV during the progression toward syncope, whereas, after 5 days of HDBR, orthostatic responses were dominated by changes in BPMCA.

Carotid and Femoral Artery Intima-Media Thickness During 6 Months of Spaceflight.

INTRODUCTION The objective was to determine the effects of 6 mo of microgravity exposure on conduit artery diameter and wall thickness. METHODS Diagnostic images of the common carotid artery (CC) and superficial femoral artery (FA) were obtained using echography which astronauts performed on themselves after receiving minimal training in the use of ultrasound imaging. Echographic video was recorded using a volume capture method directed by a trained sonographer on the ground through videoconferencing. Vessel properties were later assessed by processing the downlinked video. Data were collected from 10 astronauts who performed the echographic video capture at the beginning of the spaceflight (day 15) and near the end of the spaceflight (day 115 to 165). In-flight and postflight measurements were compared to preflight assessments. RESULTS No significant changes with spaceflight were found for CC and FA diameter. Intima-media thickness (IMT) of the CC was found to be significantly increased (12% ± 4) in all astronauts during the spaceflight (early and late flight) and remained elevated 4 d after returning to Earth. Similarly, FA IMT was increased during the flight but returned to preflight levels 4 d postflight. CONCLUSION The experiment demonstrated that, using the volume capture method of echography, untrained astronauts were able to capture enough echographic data to display vessel images of good quality for analysis. The increase in both CC and FA IMT during the flight suggest an adaptation to microgravity and to the confined environment of spaceflight which deserves further investigation.

WISE-2005: prolongation of left ventricular pre-ejection period with 56 days head-down bed rest in women

This study tested the hypothesis that prolonged physical deconditioning affects the coupling of left ventricular depolarization to its ejection (the pre‐ejection period, PEPi) and that this effect is minimized by exercise countermeasures. Following assignment to non‐exercise (Control) and exercise groups (Exercise), 14 females performed 56 days of continuous head‐down tilt bed rest. Measurements of the electrocardiogram (ECG) and stroke volume (Doppler ultrasound) during supine rest were obtained at baseline prior to (Pre) and after (Post) the head‐down tilt bed rest (HDBR) period. Compared with Pre, the PEPi was increased following head‐down tilt bed rest (main effect, P < 0.005). This effect was most dominant in the Control group [Pre = 0.038 ± 0.06 s (s.d.) versus Post = 0.054 ± 0.011 s; P < 0.001]. In the Exercise group, PEPi was 0.032 ± 0.005 s Pre and 0.038 ± 0.018 s Post; P= 0.08. Neither the QRS interval nor cardiac afterload was modified by head‐down tilt bed rest in Control or Exercise groups. Low‐dose isoprenaline infusion reversed the head‐down tilt bed rest‐induced delay in the PEPi. These results suggest that head‐down tilt bed rest leads to a delayed onset of systolic ejection following left ventricular depolarization in a manner that is affected little by the exercise countermeasure but is related to β‐adrenergic pathways. The delayed onset of systole following head‐down tilt bed rest appears to be related to mechanism(s) affecting contraction of the left ventricle rather than its depolarization.

Teles-operated echocardiography using a robotic arm and an internet connection.

The objective was to design and validate a method of tele-operated echocardiography. The method was tested in a hospital facility with an expert sonographer located in a room 10 m away from the patient. An ultrasound probe, fixed to a motorized probe holder, was located on the patient by a non-sonographer and was remotely controlled by the expert sonographer via an Internet connection. Scans were performed on 41 cardiac patients. The quality of the cardiac views obtained using tele-echocardiography was lower than that of reference echocardiography, but generated similar measurements in 93%-100% of the cases. Bland-Altman plots and statistical comparison of tele- and reference echocardiography measures revealed no differences (p > 0.05). Of the 71 valve leaks or aortic stenoses present, 61 (86%) were detected using tele-echocardiography. These results indicate that tele-echocardiography provided reliable diagnoses and acceptable measurements in 86% and 93% of cases, respectively, with no false-positive diagnoses being reported.

WISE 2005: responses of women to sublingual nitroglycerin before and after 56 days of 6° head-down bed rest

This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6° head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n = 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (+24.9 ± 7.7 and +18.8 ± 6.6 beats/min, respectively, P < 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of -12.5 ± 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ∼50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide.

Temporal artery Doppler spectrum morphology responses to tilt and LBNP as an early indicator of syncope.

OBJECTIVE In a study to identify an early hemodynamic predictor of syncope, 12 men (25-40 yr) underwent 30 min of 80 degrees head-up tilt, followed by progressive lower body negative pressure (LBNP) until presyncope. METHODS Temporal (supplying extracranial tissues: TEMP), middle cerebral (MCA), and superficial femoral (FEM) arterial flow velocity (V) and vascular resistance indices (VR) were evaluated continuously using Doppler ultrasound. Ratios of the Doppler V(MEAN) (V(MCA)/V(FEM) or V(MCA)/ V(TEMP)) were used to assess flow redistribution between these areas. RESULTS The progression of the testing protocol showed increases in vascular resistance in all territories. At presyncope, both MCA(VR) and FEM(VR) were reduced while there was a large increase in TEMP(VR). Vasoconstriction of the vascular bed supplied by the temporal artery occurred early during central hypovolemia resulting in the appearance of negative velocity deflections, which could be used for the early detection of impending syncope. Analysis of the velocity ratios showed little change until the onset of presyncope where there was an increase in V(MCA)/V(TEMP) which confirmed that vasoconstriction of the vascular bed supplied by the TEMP artery contributed to cardiac output redistribution in favor of the brain, and a reduction in V(MCA)/V(FEM) suggesting a redistribution of cardiac output toward the legs. DISCUSSION In 67% of the tests, the appearance of the negative component of V(TEMP) was an early sign of increasing TEMP(VR) that occurred before visually detectable changes in VE(FEM) or V(MCA) and within 5 min before presyncope. Such easily identifiable in real time Doppler signs allowed experimenters to anticipate test termination.

Jugular and Portal Vein Volume, Middle Cerebral Vein Velocity, and Intracranial Pressure in Dry Immersion

BACKGROUND The objective was to determine if short term exposure to dry immersion (DI) results in a cephalic fluid shift similar to what has been observed with spaceflight. METHODS Data were collected from 10 individuals at rest and during the first 2 h of dry immersion. Jugular vein (JV), portal vein (PV), and thyroid volume were measured using 3D echography. Middle cerebral vein velocity (MCVv) was determined using transcranial Doppler ultrasound. The cochlear response to audio stimulation was used to derive an estimate of intracranial pressure (dICP). RESULTS After 2 h of DI, there was a significant increase (mean ± SD) in JV (2.21 ± 1.10 mL), PV (1.05 ± 0.48 mL), and thyroid (0.428 ± 0.313 mL) volume. MCVv was also significantly increased with DI (3.90 ± 5.03 cm · s-1). There was no change in dICP with DI in part due to large individual variability. The range of dICP changes appeared to be related to MCVv, with participants with the largest increase in MCVv also showing increased dICP. DISCUSSION The results suggest that DI induces a significant cephalic fluid shift similar to what is observed with spaceflight. The increased thyroid volume suggests that cerebral tissue may also be subjected to similar fluid filtration, with implications for changes in intracranial pressure. However, despite all participants having an increase in JV and thyroid volume, only half showed an increase in dICP, suggesting that increased venous pooling alone is not sufficient to cause increased intracranial pressure.Arbeille P, Avan P, Treffel L, Zuj K, Normand H, Denise P. Jugular and portal vein volume, middle cerebral vein velocity, and intracranial pressure in dry immersion. Aerosp Med Hum Perform. 2017; 88(5):457-462.

Enhanced muscle blood flow with intermittent pneumatic compression of the lower leg during plantar flexion exercise and recovery.

This study tested the hypothesis that intermittent compression of the lower limb would increase blood flow during exercise and postexercise recovery. Data were collected from 12 healthy individuals (8 men) who performed 3 min of standing plantar flexion exercise. The following three conditions were tested: no applied compression (NoComp), compression during the exercise period only (ExComp), and compression during 2 min of standing postexercise recovery. Doppler ultrasound was used to determine superficial femoral artery (SFA) blood flow responses. Mean arterial pressure (MAP) and cardiac stroke volume (SV) were assessed using finger photoplethysmography, with vascular conductance (VC) calculated as VC = SFA flow/MAP. Compared with the NoComp condition, compression resulted in increased MAP during exercise [+3.5 ± 4.1 mmHg (mean ± SD)] but not during postexercise recovery (+1.6 ± 5.9 mmHg). SV increased with compression during both exercise (+4.8 ± 5.1 ml) and recovery (+8.0 ± 6.6 ml) compared with NoComp. There was a greater increase in SFA flow with compression during exercise (+52.1 ± 57.2 ml/min) and during recovery (+58.6 ± 56.7 ml/min). VC immediately following exercise was also significantly greater in the ExComp condition compared with the NoComp condition (+0.57 ± 0.42 ml·min-1·mmHg-1), suggesting the observed increase in blood flow during exercise was in part because of changes in VC. Results from this study support the hypothesis that intermittent compression applied during exercise and recovery from exercise results in increased limb blood flow, potentially contributing to changes in exercise performance and recovery. NEW & NOTEWORTHY Blood flow to working skeletal muscle is achieved in part through the rhythmic actions of the skeletal muscle pump. This study demonstrated that the application of intermittent pneumatic compression during the diastolic phase of the cardiac cycle, to mimic the mechanical actions of the muscle pump, accentuates muscle blood flow during exercise and elevates blood flow during the postexercise recovery period. Intermittent compression during and after exercise might have implications for exercise performance and recovery.

Altered Venous Function during Long-Duration Spaceflights

Aims: Venous adaptation to microgravity, associated with cardiovascular deconditioning, may contribute to orthostatic intolerance following spaceflight. The aim of this study was to analyze the main parameters of venous hemodynamics with long-duration spaceflight. Methods: Venous plethysmography was performed on 24 cosmonauts before, during, and after spaceflights aboard the International Space Station. Venous plethysmography assessed venous filling and emptying functions as well as microvascular filtration, in response to different levels of venous occlusion pressure. Calf volume was assessed using calf circumference measurements. Results: Calf volume decreased during spaceflight from 2.3 ± 0.3 to 1.7 ± 0.2 L (p < 0.001), and recovered after it (2.3 ± 0.3 L). Venous compliance, determined as the relationship between occlusion pressure and the change in venous volume, increased during spaceflight from 0.090 ± 0.005 to 0.120 ± 0.007 (p < 0.01) and recovered 8 days after landing (0.071 ± 0.005, arbitrary units). The index of venous emptying rate decreased during spaceflight from −0.004 ± 0.022 to −0.212 ± 0.033 (p < 0.001, arbitrary units). The index of vascular microfiltration increased during spaceflight from 6.1 ± 1.8 to 10.6 ± 7.9 (p < 0.05, arbitrary units). Conclusion: This study demonstrated that overall venous function is changed during spaceflight. In future, venous function should be considered when developing countermeasures to prevent cardiovascular deconditioning and orthostatic intolerance with long-duration spaceflight.