The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA) after prolonged head-down tilt bed rest (HDTBR). Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI). Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT), resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.
Prolonged head-down tilt bed rest (HDTBR) represents an established experimental model allowing investigating the physiologic adaptations to microgravity conditions on the ground [
Ten healthy young volunteers, all men, mean age 23 ± 2 years, were enrolled in a multidisciplinary HDTBR study endorsed by the Italian Space Agency (ASI) and taking place at the Orthopedic Hospital Valdoltra, Ankaran, Slovenia. None of the volunteers was a smoker. Medical history, physical examination, laboratory examinations, resting and stress ECG, and echocardiography have excluded any acute or chronic medical problem. The National Committee for Medical Ethics of the Slovene Ministry of Health (Ljubljana, Slovenia) approved the study. All participants were informed about the aim of the investigation, the procedures, and the methods and signed a written informed consent form according to the Declaration of Helsinki.
All participants underwent a 5-week period of bed rest in a 6° head-down tilt position (HDTBR). During the bed rest period, participants were kept strictly in bed for 24 hours a day, and none of them took any medication or underwent any physical or pharmacological countermeasure. Dietary intake was 2300 kcal/day, and water intake was 1.0–1.5 L/day. Diuresis was monitored daily, and BP and heart rate were measured every 4 hours during daytime. Body composition and hematocrit were measured before and at the end of the bed rest. Carotid and femoral ultrasound, carotid applanation tonometry, carotid-femoral pulse wave velocity (PWV), and cardiac ultrasound were performed the day before entering bed rest and within 24 hours after its termination. Vascular and cardiac examinations were performed in a quiet room, three hours after a light breakfast and after an acclimatization period of 30 min in supine position. All vascular acquisitions and readings were performed by a single operator (CM).
Body weight and fat-free mass were measured by electrical bioimpedance (BioScan 916S; Maltron International Ltd., Essex, UK).
On the right common carotid and femoral artery (CCA, CFA), two sequential acquisitions were performed using a modified commercially available equipment (MyLab30, Esaote, Firenze, Italy, with a 7.5–12 MHz broadband linear transducer, LA435), in order to obtain the following measures: (a) intima-media thickness (IMT), systolic, diastolic, and mean arterial luminal diameters; (b) centerline blood flow velocity (by conventional Duplex ultrasound); (c) shear rate values directly measured at the near and far arterial wall (by multigate Doppler system). For all ultrasound acquisitions, the angle of inclination for Doppler velocity measurements was consistently adjusted to 60°, whereas the vessel lumen was set parallel to the transducer.
(a) Longitudinal B-mode images of the right CCA and CFA with well-defined intima-media complex of the near and far wall were obtained and a loop over 5 cardiac cycles was stored. Brachial pressure and heart rate were measured during loop acquisition (Omron 705, Tokyo, Japan). Vascular ultrasound scans were analyzed by the computer-driven image analysis system MIP (Medical Image Processing; Institute of Clinical Physiology, CNR, Pisa, Italy); end-diastolic and end-systolic frames of the CCA or CFA were selected; end-diastolic far-wall IMT and minimum and maximum luminal diameters were measured within a region of interest. Arterial remodeling was assessed as a ratio of end-diastolic IMT and luminal radius (IMT/radius), where radius was calculated as minimum diameter/2. End-diastolic wall stress (kPa) was calculated as follows: diastolic BP (in kPa)
(b) In spectral Doppler recordings, peak systolic and diastolic velocities as well as systolic, diastolic and systo-diastolic flow-velocity integrals were measured, both for CCA and CFA. Resistive index was calculated as follows: (peak systolic velocity − peak diastolic velocity)/peak systolic velocity. Systolic and diastolic volumetric flows per beat were calculated as systolic and diastolic arterial area (Π
(c) Shear rate was assessed by a validated multigate Doppler system determining a flow velocity profile from a matrix of 128-point power spectral densities corresponding to 128 different depths along the Doppler beam [
Carotid applanation tonometry was performed on the right CCA using a validated system (PulsePen; Diatecne, Milan, Italy) [
Carotid-femoral PWV was measured according to current guidelines [
Cardiac ultrasound was performed as previously described [
Quantitative data are expressed as mean ± sd. Paired
During the bed rest period, body weight, BMI, fat FFM and Doppler-derived stroke volume, and flow-velocity integral in ascending aorta diminished, peripheral BP did not change significantly, and heart rate and hematocrit increased (Table
Main anthropometric and hemodynamic characteristics and hematocrit in 10 healthy volunteers before and after HDTBR.
Before | After |
| |
---|---|---|---|
Weight (kg) |
|
|
|
BMI (kg/m2) |
|
|
|
Fat-free mass (kg) |
|
|
|
Hematocrit (%) |
|
|
|
Systolic BP (mmHg) |
|
|
|
Diastolic BP (mmHg) |
|
|
|
Pulse pressure (mmHg) |
|
|
|
Heart rate (bpm) |
|
|
|
Stroke volume (mL) |
|
|
|
FVI ascending aorta (cm) |
|
|
|
BMI: body mass index; FFM: fat-free mass; BP: blood pressure; FVI: flow-velocity integral.
After 5 weeks of HDTBR, no significant changes were observed in CCA geometry and stiffness (Table
Common carotid artery and common femoral artery structure, stiffness, and flow before and after HDTBR in 10 healthy volunteers.
CCA |
|
CFA |
| |||
---|---|---|---|---|---|---|
Before | After | Before | After | |||
IMT ( |
|
|
|
|
|
|
Diameter minimum (mm) |
|
|
|
|
|
|
Diameter maximum (mm) |
|
|
|
|
|
|
Δ diameter (mm) |
|
|
|
|
|
|
End-diastolic IMT/radius |
|
|
|
|
|
|
End-diastolic wall stress (kPa) |
|
|
|
|
|
|
Beta index |
|
|
|
|
|
|
Peak velocity systolic (cm/s) |
|
|
|
|
|
|
Peak velocity diastolic (cm/s) |
|
|
|
|
|
|
Resistive index |
|
|
|
|
|
|
Mean flow per beat (mL) |
|
|
|
|
|
|
Systolic flow per beat (mL) |
|
|
|
|
|
|
Diastolic flow per beat (mL) |
|
|
|
|
|
|
Ratio syst/diast flow per beat |
|
|
|
|
|
|
WSR peak near wall (s−1) |
|
|
|
|
|
|
WSR peak far wall (s−1) |
|
|
|
|
|
|
IMT: intima-media thickness; WSR: wall shear rate.
Responses in flow velocities and volumes differed between CCA and CFA. In CCA, peak systolic and diastolic velocity did not change significantly during the bed rest period. In CFA, both peak systolic and diastolic velocities increased, but the increase was higher for diastolic velocity and, consequently, the resistive index decreased. Systolic volumetric flow per beat remained stable both in CCA and in CFA. In contrast, diastolic volumetric flow showed a trend to decrease in CCA, whereas it increased in CFA (Table
Wall shear rate at near and far arterial wall did not change during HDTBR either in CCA or in CFA (Table
Carotid femoral PWV and AIx did not change after 5 weeks of HDTBR, while local carotid pulse pressure and pulse pressure index decreased and pressure amplification index increased (Table
Carotid-femoral pulse wave velocity and carotid pressure waveform analysis before and after HDTBR in 10 healthy volunteers.
Before | After |
| |
---|---|---|---|
C-F PWV (m/s) |
|
|
|
Local SBP (mmHg) |
|
|
|
Local PP (mmHg) |
|
|
|
PPI |
|
|
|
AIx |
|
|
|
Pressure amplification |
|
|
|
C-F PWV: carotid-femoral pulse wave velocity; SBP: systolic blood pressure; PP: pulse pressure; PPI: pulse pressure index; AIx: augmentation index.
The present study compares the response of large elastic and muscular artery to prolonged HDTBR and provides some novel information about arterial mechanics and flow dynamics during deconditioning that are summarized in Figure
Schematic representation of changes observed at common carotid level, at femoral artery level, and in central hemodynamics after 35-days head-down tilt bed rest in 10 young healthy volunteers.
In our young healthy volunteers, an inward remodeling of femoral artery, due to luminal diameter reduction, and a diminution of circumferential wall stress was observed after a 35-day bed rest. Carotid geometry, on the other hand, was not significantly influenced by deconditioning, a finding confirming the differences in response of carotid and femoral artery to bed rest. Observed reduction in femoral artery diameter is in agreement with results of the Berlin Bed Rest (BBR) study [
In contrast with results of the second BBR study [
Previous studies evaluating the effect of unloading on the blood flow in the lower extremity have produced inconclusive evidence. In the BBR study [
Our study is the first to look separately at the systolic and diastolic flow velocities and volumes, both at CCA and CFA levels. In CCA, the diastolic component of volumetric flow after HDTBR showed trend to decrease, and the changes in both diastolic and mean volumetric flow were directly related to changes in stroke volume and in flow-velocity integral in ascending aorta. This observation suggests that carotid artery flow simply mirrors the changes occurring in aortic flow. In contrast, in CFA, the diastolic component of local blood flow significantly increased and, consequently, the resistive index and the ratio of systolic to diastolic flow volume decreased. This behavior may reflect a decrease in local vascular resistance at arteriolar level of the leg. Based upon evidence from previous HDTBR studies, a reduction of sympathetic firing to lower limb vessels could explain our finding. Stout et al. reported that during simulated microgravity, a cutaneous microcirculatory vasodilation is more marked in the lower than in the upper part of the body, being related to a baroreflex-mediated withdrawal of a sympathetic tone [
Wall shear rate, describing the tangential force exerted by the flow stream on the arterial wall, did not change during the study, either in elastic or muscular artery. A role of shear rate in arterial diameter control was suggested by a direct relationship between near- and far-wall shear rate and CCA luminal diameter at baseline conditions [
The lack of bed rest induced changes in indices of either local carotid and femoral stiffness or segmental aortic stiffness (Table
This study has several limitations. First, the population studied is small and consists only of men. Second, all participants were young, and thus the results do not provide information on the effect of bed rest on arterial structure and function in older subjects. Third, vascular examinations were performed only one day before and one day after HDTBR; consequently, we could not evaluate a sequence of changes over the bed rest period or after termination of bed rest. Fourth, plasma viscosity was not measured, so that only wall shear rate but not wall shear stress could be assessed. Furthermore, the experimental model used in this study, although established for simulating unloading conditions related to microgravity, does not allow separating the effects of a reduced muscle activity from those of a reduced gravitational acceleration. Finally, AIx values were not adjusted for heart rate. Due to the significant increase in heart rate observed after bed rest, we could have overestimated AIx and underestimated a reduction in wave reflection.
An integrated vascular approach combining established and experimental ultrasound, arterial contour wave analysis, and pulse wave velocity assessment was exploited to investigate the adaptation of large arteries to microgravity conditions simulated by HDTBR. Prolonged HDTBR showed a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused. Changes in CCA blood flow seem to reflect bed rest induced decrease in stroke volume and aortic flow and did not alter CCA geometry. Reduction in CFA luminal diameter and inward remodeling may result from reduced metabolic demand in a downstream unloaded muscle tissue, and changes in CFA flow may reflect decrease in local vascular resistance secondary to withdrawal of a sympathetic tone. Observed changes in systemic hemodynamics that included decrease in local pulse pressure and pulse pressure index and increase in carotid-brachial pressure amplification suggest a reduction of wave reflection from a vasodilated periphery (Figure
In the prospect of improving the management of subjects undergoing real microgravity conditions, data obtained in this study confirm the indication to active counter-measurements aimed to prevent unloading-related sarcopenia as well as the possible usefulness of common carotid artery as a “window” to monitor central hemodynamic changes.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors are grateful to Dr. Bostjan Simunic, Institute of Kinesiology Research, University of Primorska, Koper, and to the personnel at the Valdoltra Orthopaedic Hospital in Ankaran (Slovenia) for their valuable medical assistance and technical support. This study was partly supported by grants of the Italian Space Agency (ASI), projects Disorders of Motor and Cardio-Respiratory Control (DMCR) and Osteoporosis and Muscle Atrophy (OSMA), and a Grant (PRIN 2010-2011) of the Italian Ministry of University and Research (MIUR).