Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure.

PURPOSE: Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (- 6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9 days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested. METHODS: RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values. RESULTS: RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0. CONCLUSION: 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes.

Effects of 5 days of head-down bed rest, with and without short-arm centrifugation as countermeasure, on cardiac function in males (BR-AG1 study).

This study examined cardiac remodeling and functional changes induced by 5 days of head-down (-6°) bed rest (HDBR) and the effectiveness of short-arm centrifugation (SAC) in preventing them in males. Twelve healthy men (mean age: 33 ± 7) were enrolled in a crossover design study (BR-AG1, European Space Agency), including one sedentary (CTRL) and two daily SAC countermeasures (SAC1, 30 min continuously; SAC2, 30 min intermittently) groups. Measurements included plasma and blood volume and left ventricular (LV) and atrial (LA) dimensions by transthoracic echocardiography (2- and 3-dimensional) and Doppler inflows. Results showed that 5 days of HDBR had a major impact on both the geometry and cardiac function in males. LV mass and volume decreased by 16 and 14%, respectively; LA volume was reduced by 36%; Doppler flow and tissue Doppler velocities were reduced during early filling by 18 and 12%, respectively; and aortic flow velocity time integral was decreased by 18% with a 3% shortening of LV ejection time. These modifications were presumably due to decreased physiological loading and dehydration, resulting in reduced plasma and blood volume. All these changes were fully reversed 3 days after termination of HDBR. Moreover, SAC was not able to counteract these changes, either when applied continuously or intermittently.

The role of echocardiography in the assessment of cardiac function in weightlessness-Our experience during parabolic flights.

Parabolic flight (PF) elicits changes in hydrostatic pressure gradients, resulting in increase (at 0Gz) or decrease (at 1.8Gz) in cardiac preload. The magnitude of these changes on left ventricular (LV) and atrial (LA) volumes, as well as on myocardial velocities, strain and strain rates, is largely unknown. Using real-time 3D (RT3DE) and Doppler tissue echocardiographic imaging (DTI) during PF in normal subjects in standing position, we showed that both LV and LA volumes were decreased at 1.8Gz and increased at 0Gz by about 20% and 40%, respectively. Previous 2D or M-mode studies underestimated such changes. Also, preload dependence was confirmed for systolic and diastolic velocities, and peak systolic strain, while strain rates were preload independent, probably reflecting intrinsic myocardial properties. Low body negative pressure at -50mmHg applied during 0Gz was effective in restoring 1Gz levels. RT3DE and DTI during PF are feasible, allowing the evaluation of the cardiac function under different loading conditions.

Evaluation of alterations on mitral annulus velocities, strain, and strain rates due to abrupt changes in preload elicited by parabolic flight.

We tested the hypothesis that in normal subjects, cardiac tissue velocities, strain, and strain rates (SR), measured by Doppler tissue echocardiography (DTE), are preload dependent. To accomplish it, immediately preceding image acquisition, reversible, repeatable, acute nonpharmacological changes in preload were induced by parabolic flight. DTE has been proposed as a new approach to assess left ventricular regional myocardial function by computing tissue velocities, strain, and SR. However, preload dependence of these parameters in normal subjects still remains controversial. DTE images (Philips) were obtained in 10 normal subjects in standing upright position at normogravity (1 Gz), hypergravity (1.8 Gz), and microgravity (0 Gz) with and without -50 mmHg lower body negative pressure (LBNP). Myocardial velocity curves in the basal interventricular septum were reconstituted offline from DTE images, from which peak systolic (S'), early (E') and late (A') diastolic velocities, SR, and peak systolic strain (PSepsilon) were measured and averaged over four beats. At 1.8 Gz (reduced venous return), S', E', and A' decreased by 21%, 21%, and 26%, respectively, compared with 1-Gz values, while at 0 Gz (augmented venous return), E', A', and PSepsilon increased by 57%, 53%, and 49%, respectively. LBNP reduced E' and PSepsilon. In conclusion, our results were in agreement with those obtained in animal models, in which preload was changed in a controlled, acute, and reversible manner, and image acquisition was performed immediately following preload modifications. The hypothesis of preload dependence was confirmed for S', E', A', and PSepsilon, while SR appeared to be preload independent, probably reflecting intrinsic myocardial properties.

[Dynamics of ECG voltage in changing gravity].

Comparative analysis of the QRS voltage response to gravity variations was made using the data about 26 normal human subjects collected in parabolic flights (CNERS-AIRBUS A300 Zero-G, n=23; IL-76MD, n=3) and during the tilt test (head-up tilt at 70 degrees for a min and head-down tilt at-15 degrees for 5 min, n=14). Both the parabolic flights and provocative tilt tests affected R-amplitude in the Z lead. During the hypergravity episodes it was observed in 95% of cases with the mean gain of 16% and maximal--56%. On transition to the horizontal position, the Rz-amplitude showed a rise in each subject (16% on the average). In microgravity, the Rz-amplitude reduced in 95% of the observations. The voltage decline averaged 18% and reached 49% at the maximum. The head-down tilt was conducive to Rz reduction in 78% of observations averaging 2%. Analysis of the ECG records under changing gravity when blood redistribution developed within few seconds not enough for serious metabolic shifts still revealed QRS deviations associated exclusively with the physical factors, i.e., alteration in tissue conduction and distance to electrodes. Our findings can stand in good stead in evaluation of the dynamics of predictive ECG parameters during long-term experiments leading to changes as in tissue conduction, so metabolism.

Objective evaluation of changes in left ventricular and atrial volumes during parabolic flight using real-time three-dimensional echocardiography.

We tested the feasibility of real-time three-dimensional (3D) echocardiographic (RT3DE) imaging to measure left heart volumes at different gravity during parabolic flight and studied the effects of lower body negative pressure (LBNP) as a countermeasure. Weightlessness-related changes in cardiac function have been previously studied during spaceflights using both 2D and 3D echocardiography. Several technical factors, such as inability to provide real-time analysis and the need for laborious endocardial definition, have limited its usefulness. RT3DE imaging overcomes these limitations by acquiring real-time pyramidal data sets encompassing the entire ventricle. RT3DE data sets were obtained (Philips 7500, X3) during breath hold in 16 unmedicated normal subjects in upright standing position at different gravity phases during parabolic flight (normogravity, 1 Gz; hypergravity, 1.8 Gz; microgravity, 0 Gz), with LBNP applied (-50 mmHg) at 0 Gz in selected parabolas. RT3DE imaging during parabolic flight was feasible in 14 of 16 subjects. Data were analyzed (Tomtec) to quantify left ventricular (LV) and atrial (LA) volumes at end diastole and end systole, which significantly decreased at 1.8 Gz and increased at 0 Gz. While ejection fraction did not change with gravity, stroke volume was reduced by 16% at 1.8 Gz and increased by 20% at 0 Gz, but it was not significantly different from 1 Gz values with LBNP. RT3DE during parabolic flight is feasible and provides the basis for accurate quantification of LV and LA volume changes with gravity. As LBNP counteracted the increase of LV and LA volumes caused by changes in venous return, it may be effectively used for preventing cardiac dilatation during 0 Gz.

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Effect of changing the gravity vector on respiratory output and control.

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately -14%), shifting to supine posture (transition time approximately 15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.

ECG voltage modifications as response to gravity changes.

The aim of the study was to analyze ECG (QRS) voltage responses to body fluid shift due to gravity chances. Acute changes in gravity were created by two ways: 1) changes in gravity value during parabolic flights (within 27 subjects 45 ECG have been analyzed); 2) changes in gravity direction due to rotation of the body during postural tests (within 11 subjects 14 ECG have been analyzed). Results and conclusions. Gravity change leads to body fluid shift and changes of intrathoracic organs and tissues electroconduction. It influences on ECG voltage. During parabolic flights in up-right position: R amplitude in Z axis increases in hypergravity (+0.19 mV) and decreases in microgravity (-0.24 mV). During postural tests, R amplitude in Z axis increases in orthostatic position (+0.09 mV) and decreases in antiorthostatic position (-0.025 mV). Changes in QRS voltage during parabolic flights are more important than during postural tests. This could be due to more effective blood redistribution during parabolic flights.

Changes in Doppler mitral inflow patterns during parabolic flight.

Aim of the study was to evaluate by transthoracic Doppler the alterations in mitral inflow velocity pattern caused by acute changes in loading conditions occurring during parabolic flights. Each parabola included normogravity (1 Gz, 1 min), mild hypergravity (1.8 Gz, 20 sec), microgravity (0 Gz, 24 sec) and mild hypergravity (1.8 Gz, 20 sec) phases. Pulsed-Doppler images were digitally acquired in 11 unmedicated subjects (46 +/- 5 years), in standing upright position and supine resting. Doppler profiles were semi-automatically traced and inflow parameters extracted and averaged onto three consecutive beats. Only in standing position, significant alterations during microgravity (p<0.05) were noted in several parameters.

Feasibility of real-time 3D echocardiography in weightlessness during parabolic flight.

Aim of the study was to test the feasibility of transthoracic real-time 3D (Philips) echocardiography (RT3D) during parabolic flight, to allow direct measurement of heart chambers volumes modifications during the parabola. One RT3D dataset corresponding to one cardiac cycle was acquired at each gravity phase (1 Gz, 1.8 Gz, 0 Gz, 1.8 Gz) during breath-hold in 8 unmedicated normal subjects (41 +/- 8 years old) in standing upright position. Preliminary results, obtained by semi-automatically tracing left ventricular (LV) and left atrial (LA) endocardial contours in multiple views (Tomtec), showed a significant (p<0.05) reduction, compared to 1 Gz, of LV and LA volumes with 1.8 Gz, and a significant increase with 0 Gz. Further analysis will focus on the right heart.

Effect of gravity and posture on lung mechanics.

The volume-pressure relationship of the lung was studied in six subjects on changing the gravity vector during parabolic flights and body posture. Lung recoil pressure decreased by approximately 2.7 cmH(2)O going from 1 to 0 vertical acceleration (G(z)), whereas it increased by approximately 3.5 cmH(2)O in 30 degrees tilted head-up and supine postures. No substantial change was found going from 1 to 1.8 G(z). Matching the changes in volume-pressure relationships of the lung and chest wall (previous data), results in a decrease in functional respiratory capacity of approximately 580 ml at 0 G(z) relative to 1 G(z) and of approximately 1,200 ml going to supine posture. Microgravity causes a decrease in lung and chest wall recoil pressures as it removes most of the distortion of lung parenchyma and thorax induced by changing gravity field and/or posture. Hypergravity does not greatly affect respiratory mechanics, suggesting that mechanical distortion is close to maximum already at 1 G(z). The end-expiratory volume during quiet breathing corresponds to the mechanical functional residual capacity in each condition.

Changes of decartograms under gravitational acceleration and microgravity.

The Decarto technique was used to study the orthogonal ECGs recorded in 23 subjects during parabolic flights (44 records). A parameter of the instantaneous decartograms, namely the activation area (AA), which is the total area of the depolarization front projection on the image sphere, was analyzed. We compared the values of AA during the periods of horizontal flight, upward parts of all parabolas, and the initial 10 s of microgravity of all parabolas. According to the characteristics of the vectorcardiograms and AA, all subjects were subdivided into 3 groups: with increased electric activity of the right ventricle (I), the left ventricle (II) and both ventricles (III). Changes of AA with change of gravitational levels in these groups showed some differences. In groups I and II, the AA of the initial part of the QRS complex increased during microgravity and decreased during hypergravity. In group III it decreased during microgravity and changed variously during hypergravity. The AA of the middle part of the QRS complex decreased during microgravity and increased during hypergravity, and these changes were more pronounced in group III. The changes of AA in groups I and II may be explained by the Brody effect. In group III, AA seems to be influenced by some additional factors, possibly by changes in the intramyocardial or intraventricular blood volume. The AA of the last part of the QRS complex increased during microgravity and decreased during hypergravity in all groups. This may be explained by an effect of mutual neutralization of depolarization fronts related to the changes of the QRS duration.(Fig. 3, Ref. 4)

Effect of gravity on chest wall mechanics.

Chest wall mechanics was studied in four subjects on changing gravity in the craniocaudal direction (G(z)) during parabolic flights. The thorax appears very compliant at 0 G(z): its recoil changes only from -2 to 2 cmH(2)O in the volume range of 30-70% vital capacity (VC). Increasing G(z) from 0 to 1 and 1.8 G(z) progressively shifted the volume-pressure curve of the chest wall to the left and also caused a fivefold exponential decrease in compliance. For lung volume <30% VC, gravity has an inspiratory effect, but this effect is much larger going from 0 to 1 G(z) than from 1 to 1.8 G(z). For a volume from 30 to 70% VC, the effect is inspiratory going from 0 to 1 G(z) but expiratory from 1 to 1.8 G(z). For a volume greater than approximately 70% VC, gravity always has an expiratory effect. The data suggest that the chest wall does not behave as a linear system when exposed to changing gravity, as the effect depends on both chest wall volume and magnitude of G(z).

Changes in left ventricular size during parabolic flights by two-dimensional echocardiography and level set method.

This study aims to evaluate changes on cardiac chambers size, induced by gravitational stresses. During parabolic flight, seven subjects underwent 2-D transthoracic echocardiography at three different gravity phases (1 Gz, 1.8 Gz, and 0 Gz). LV endocardial borders were detected applying a semi-automatic segmentation procedure based on level set methods. LV cavity area was computed frame-by-frame for a whole cardiac cycle during each gravity phase. Expected modifications in LV area with different gravity were found: at 1.8 Gz, end-diastolic (ED) and end-systolic (ES) areas were significantly (p<0.05) reduced of 10.7 +/- 5.4% and 21.6 +/- 11.1% respectively, compared to 1 Gz values, while they were increased of 11.2 +/- 5.4% and 11.1 +/- 6% during 0 Gz. Fractional area change was augmented of 20.9 +/- 29.1% at 1.8 Gz, while it remained unchanged at 0 Gz, compared with 1 Gz values. Furthermore, LV filling due to atrial contraction was increased at 0 Gz of 39 +/- 35.6%.

Time-variant spectral analysis of heart rate variability during parabolic flight with and without LBNP.

Modifications of autonomic activity during parabolic flight were studied by a time-variant model able to estimate low (LF, 0.04-0.14 Hz) and high (HF, 0.14-0.35 Hz) frequency spectral components on a beat-to-beat basis. Ten subjects were studied with and without lower body negative pressure (LBNP). ECG and Gz load were digitized (500 Hz) and RR interval variability series extracted. Beat-to-beat mean RR, variance, LF and HF power were obtained. One-way ANOVA (p<0.01) was used to compare values obtained during starting 1Gz (I), first 1.8Gz (II), 0Gz (III), second 1.8Gz (IV), ending 1Gz (V). Without LBNP, total and LF power increased during 0Gz to 1.69 +/- 1.41 and 2.87 +/- 4.66 respectively (mean +/- SD, normalized by phase I value). With LBNP, their change during 0Gz (1.38 +/- 1.37 and 1.54 +/- l.04 respectively) reached significance only with phase II and phase V. Phase I HF power was higher than in the other phases, both without and with LBNP.

Parasympathetic activity during parabolic flight, effect of LBNP during microgravity.

BACKGROUND/HYPOTHESIS: During parabolic flight, in the standing position, changes are partly due to an acute shift in fluid between the lower extremities, the head and the thorax (Vaïda P, et al. J Appl Physiol 1997; 82:1091-7; and Bailliart O, et al. J Appl Physiol 1998; 85:2100-5). We hypothesized that modifications of parasympathetic activity associated with changes in hydrostatic pressure gradients induced by changes in gravity could be detected by analysis of short time periods. METHODS: We assessed heart rate variability (HRV) in 11 healthy volunteers by indices of temporal analysis (NN, SDNN, RMSSD) and normalized indices such as coefficients of variation CV-SDNN and CV-RMSSD and ratio SDNN/RMSSD. A lower body negative pressure (LBNP) at -50 mm Hg was randomly applied during the microgravity phase (0 Gz) to counteract the lack of hydrostatic pressure in the lower part of the body. RESULTS: NN, CV-SDNN and CV-RMSSD decreased during hypergravity phases and increased during microgravity and during early normogravity (1 Gz) period at the end of parabolas. With LBNP changes are less pronounced at 0 Gz and in the 1 Gz post parabolic period. CONCLUSION: We concluded that parasympathetic nervous activity is recordable by temporal analysis of HRV during short periods of time. LBNP applied during 0 Gz phase reduced the parasympathetic activation at 0 Gz and post parabolic 1 Gz.

Changes in lower limb volume in humans during parabolic flight.

Variations in gravity [head-to-foot acceleration (Gz)] induce hemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs to blood pooling or shifting during the different gravity phases of a parabolic flight, we measured instantaneous thigh and calf girths by using strain-gauge plethysmography in five healthy volunteers. From these circumferential measurements, segmental leg volumes were calculated at 1, 1.7, and 0 Gz. During hypergravity, leg segment volumes increased by 0.9% for the thigh (P < 0.001) and 0.5% for the calf (P < 0.001) relative to 1-Gz conditions. After sudden exposure to microgravity following hypergravity, leg segment volumes were reduced by 3.5% for the thigh (P < 0.001) and 2.5% for the calf (P < 0.001) relative to 1.7-Gz conditions. Changes were more pronounced at the upper part of the leg. Extrapolation to the whole lower limb yielded an estimated 60-ml increase in leg volume at the end of the hypergravity phase and a subsequent 225-ml decrease during microgravity. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during hypergravity and weightlessness.

Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flights.

Data from the Spacelab Life Sciences-1 (SLS-1) mission have shown sustained but moderate increase in pulmonary diffusing capacity (DL). Because of the occupational constraints of the mission, data were only obtained after 24 h of exposure to microgravity. Parabolic flights are often used to study some effects of microgravity, and we measured changes in DL occurring at the very onset of weightlessness. Measurements of DL, membrane diffusing capacity, and pulmonary capillary blood volume were made in 10 male subjects during the 20-s 0-G phases of parabolic flights performed by the "zero-G" Caravelle aircraft. Using the standardized single-breath technique, we measured DL for CO and nitric oxide simultaneously. We found significant increases in DL for CO (62%), in membrane diffusing capacity for CO (47%), in DL for nitric oxide (47%), and in pulmonary capillary blood volume (71%). We conclude that major changes in the alveolar membrane gas transfers and in the pulmonary capillary bed occur at the very onset of microgravity. Because these changes are much greater than those reported during sustained microgravity, the effects of rapid transition from hypergravity to microgravity during parabolic flights remain questionable.

Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer.

NO and CO lung transfer values (TL) were measured separately in 14 healthy subjects (7 men, 7 women), using the single breath technique. Five repetitive maneuvers were performed by each subject for TLNO and TLCO determinations. The inspired mixture contained either 8 ppm NO or 0.25% CO, with 2% He, 21% O2 in N2. In order to measure an appreciable fraction of NO in the alveolar gas it was necessary to shorten the breath holding time to 3 sec. TLNO was about five times greater than TLCO. This result suggests that the specific conductance of blood (theta) for NO is very high and that the second term of the second member of the equation 1/TLNO = 1/DmNO + 1/(theta NO.Qc) is therefore negligible. DmCO and Qc values can thus be computed from TLNO and TLCO measurements. The results obtained with this method are very close to those reported in the literature; for men DmCO = 79.0 +/- 14.3 ml.min-1.Torr-1, Qc = 78.0 +/- 13.2 ml and for women DmCO = 59.0 +/- 10.1 ml.min-1.Torr-1, Qc = 59.5 +/- 11.6 ml.