Danielle K. Greaves

Cardiovascular regulation during long-duration spaceflights to the International Space Station.

Early evidence from long-duration flights indicates general cardiovascular deconditioning, including reduced arterial baroreflex gain. The current study investigated the spontaneous baroreflex and markers of cardiovascular control in six male astronauts living for 2-6 mo on the International Space Station. Measurements were made from the finger arterial pressure waves during spontaneous breathing (SB) in the supine posture pre- and postflight and during SB and paced breathing (PB, 0.1 Hz) in a seated posture pre- and postflight, as well as early and late in the missions. There were no changes in preflight measurements of heart rate (HR), blood pressure (BP), or spontaneous baroreflex compared with in-flight measurements. There were, however, increases in the estimate of left ventricular ejection time index and a late in-flight increase in cardiac output (CO). The high-frequency component of RR interval spectral power, arterial pulse pressure, and stroke volume were reduced in-flight. Postflight there was a small increase compared with preflight in HR (60.0 ± 9.4 vs. 54.9 ± 9.6 beats/min in the seated posture, P < 0.05) and CO (5.6 ± 0.8 vs. 5.0 ± 1.0 l/min, P < 0.01). Arterial baroreflex response slope was not changed during spaceflight, while a 34% reduction from preflight in baroreflex slope during postflight PB was significant (7.1 ± 2.4 vs. 13.4 ± 6.8 ms/mmHg), but a smaller average reduction (25%) during SB (8.0 ± 2.1 vs. 13.6 ± 7.4 ms/mmHg) was not significant. Overall, these data show no change in markers of cardiovascular stability during long-duration spaceflight and only relatively small changes postflight at rest in the seated position. The current program routine of countermeasures on the International Space Station provided sufficient stimulus to maintain cardiovascular stability under resting conditions during long-duration spaceflight.

Diving Heart Rate Development in Postnatal Harbour Seals, Phoca vitulina

Harbour seals, Phoca vitulina, dive from birth, providing a means of mapping the development of the diving response, and so our objective was to investigate the postpartum development of diving bradycardia. The study was conducted May–July 2000 and 2001 in the St. Lawrence River Estuary (48°41′N, 68°01′W). Both depth and heart rate (HR) were remotely recorded during 86,931 dives (ages 2–42 d, n = 15) and only depth for an additional 20,300 dives (combined data covered newborn to 60 d, n = 20). The mean dive depth and mean dive durations were conservative during nursing (2.1 ± 0.1 m and 0.57 ± 0.01 min, range = 0–30.9 m and 0–5.9 min, respectively). The HR of neonatal pups during submersion was bimodal, but as days passed, the milder of the two diving HRs disappeared from their diving HR record. By 15 d of age, most of the dive time was spent at the lower diving bradycardia rate. Additionally, this study shows that pups are born with the ability to maintain the lower, more fully developed dive bradycardia during focused diving but do not do so during shorter routine dives.

Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6-mo spaceflight in male and female astronauts

Removal of the normal head-to-foot gravity vector and chronic weightlessness during spaceflight might induce cardiovascular and metabolic adaptations related to changes in arterial pressure and reduction in physical activity. We tested hypotheses that stiffness of arteries located above the heart would be increased postflight, and that blood biomarkers inflight would be consistent with changes in vascular function. Possible sex differences in responses were explored in four male and four female astronauts who lived on the International Space Station for 6 mo. Carotid artery distensibility coefficient (P = 0.005) and β-stiffness index (P = 0.006) reflected 17-30% increases in arterial stiffness when measured within 38 h of return to Earth compared with preflight. Spaceflight-by-sex interaction effects were found with greater changes in β-stiffness index in women (P = 0.017), but greater changes in pulse wave transit time in men (P = 0.006). Several blood biomarkers were changed from preflight to inflight, including an increase in an index of insulin resistance (P < 0.001) with a spaceflight-by-sex term suggesting greater change in men (P = 0.034). Spaceflight-by-sex interactions for renin (P = 0.016) and aldosterone (P = 0.010) indicated greater increases in women than men. Six-month spaceflight caused increased arterial stiffness. Altered hydrostatic arterial pressure gradients as well as changes in insulin resistance and other biomarkers might have contributed to alterations in arterial properties, including sex differences between male and female astronauts.

Short term variability of blood pressure: effects of lower body negative pressure and long duration bed rest

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Womens International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.

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.

Non-contact hemodynamic imaging reveals the jugular venous pulse waveform

Cardiovascular monitoring is important to prevent diseases from progressing. The jugular venous pulse (JVP) waveform offers important clinical information about cardiac health, but is not routinely examined due to its invasive catheterisation procedure. Here, we demonstrate for the first time that the JVP can be consistently observed in a non-contact manner using a photoplethysmographic imaging system. The observed jugular waveform was strongly negatively correlated to the arterial waveform (r = −0.73 ± 0.17), consistent with ultrasound findings. Pulsatile venous flow was observed over a spatially cohesive region of the neck. Critical inflection points (c, x, v, y waves) of the JVP were observed across all participants. The anatomical locations of the strongest pulsatile venous flow were consistent with major venous pathways identified through ultrasound.

Prior head-down tilt does not impair the cerebrovascular response to head-up tilt

The hypothesis that cerebrovascular autoregulation was not impaired during head-up tilt (HUT) that followed brief exposures to varying degrees of prior head-down tilt (HDT) was tested in 10 healthy young men and women. Cerebral mean flow velocity (MFV) and cardiovascular responses were measured in transitions to a 60-s period of 75° HUT that followed supine rest (control) or 15 s HDT at -10°, -25°, and -55°. During HDT, heart rate (HR) was reduced for -25° and -55°, and cardiac output was lower at -55° HDT. MFV increased during -10° HDT, but not in the other conditions even though blood pressure at the middle cerebral artery (BPMCA) increased. On the transition to HUT, HR increased only for -55° condition, but stroke volume and cardiac output transiently increased for -25° and -55°. Total peripheral resistance index decreased in proportion to the magnitude of HDT and recovered over the first 20 s of HUT. MFV was significantly less in all HDT conditions compared with the control in the first 5-s period of HUT, but it recovered quickly. An autoregulation correction index derived from MFV recovery relative to BPMCA decline revealed a delay in the first 5 s for prior HDT compared with control but then a rapid increase to briefly exceed control after -55° HDT. This study showed that cerebrovascular autoregulation is modified by but not impaired by brief HDT prior to HUT and that cerebral MFV recovered quickly and more rapidly than arterial blood pressure to protect against cerebral hypoperfusion and potential syncope.

Cardiac output by pulse contour analysis does not match the increase measured by rebreathing during human spaceflight

Pulse contour analysis of the noninvasive finger arterial pressure waveform provides a convenient means to estimate cardiac output (Q̇). The method has been compared with standard methods under a range of conditions but never before during spaceflight. We compared pulse contour analysis with the Modelflow algorithm to estimates of Q̇ obtained by rebreathing during preflight baseline testing and during the final month of long-duration spaceflight in nine healthy male astronauts. By Modelflow analysis, stroke volume was greater in supine baseline than seated baseline or inflight. Heart rate was reduced in supine baseline so that there were no differences in Q̇ by Modelflow estimate between the supine (7.02 ± 1.31 l/min, means ± SD), seated (6.60 ± 1.95 l/min), or inflight (5.91 ± 1.15 l/min) conditions. In contrast, rebreathing estimates of Q̇ increased from seated baseline (4.76 ± 0.67 l/min) to inflight (7.00 ± 1.39 l/min, significant interaction effect of method and spaceflight, P < 0.001). Pulse contour analysis utilizes a three-element Windkessel model that incorporates parameters dependent on aortic pressure-area relationships that are assumed to represent the entire circulation. We propose that a large increase in vascular compliance in the splanchnic circulation invalidates the model under conditions of spaceflight. Future spaceflight research measuring cardiac function needs to consider this important limitation for assessing absolute values of Q̇ and stroke volume.NEW & NOTEWORTHY Noninvasive assessment of cardiac function during human spaceflight is an important tool to monitor astronaut health. This study demonstrated that pulse contour analysis of finger arterial blood pressure to estimate cardiac output failed to track the 46% increase measured by a rebreathing method. These results strongly suggest that alternative methods not dependent on pulse contour analysis are required to track cardiac function in spaceflight.

Elevated End-Tidal Pco 2 During Long-Duration Spaceflight

BACKGROUND Elevated ambient Pco2 in the International Space Station (ISS) has been cited as a potential contributor to the vision impairment intracranial pressure syndrome (VIIP), a significant health risk for astronauts during long-duration space missions. The elevation in ambient Pco2 is rather modest and normal respiratory compensation could minimize the impact on arterial Pco2. METHODS In nine male astronauts, breaths measured prior to a rebreathing maneuver were examined to assess inspired and end-tidal Pco2 during upright seated preflight and in-flight conditions. RESULTS Inspired Pco2 increased from preflight baseline (0.6 ± 0.1 mmHg) to in flight (3.8 ± 0.4 mmHg). End-tidal Pco2 also increased from preflight baseline (36.0 ± 3.2 mmHg) to in flight (42.1 ± 3.7 mmHg). The difference between end-tidal Pco2 comparing in flight to preflight (6.1 ± 1.6 mmHg) was greater than the difference between inspired Pco2 comparing preflight to in flight (3.3 ± 0.5 mmHg). DISCUSSION The greater increase in end-tidal vs. inspired Pco2 might reflect alveolar hypoventilation due to differences in ventilatory control with spaceflight. These data suggest that further studies should focus on arterial Pco2 and acid-base balance to determine if CO2 dilates cerebral and retinal vessels and might contribute to the incidence of VIIP in astronauts. Hughson RL, Yee NJ, Greaves DK. Elevated end-tidal Pco2 during long-duration spaceflight. Aerosp Med Hum Perform. 2016; 87(10):894-897.

Long-duration bed rest modifies sympathetic neural recruitment strategies in males and females

To understand the impact of physical deconditioning with head-down tilt bed rest (HDBR) on the malleability of sympathetic discharge patterns, we studied 1) baseline integrated muscle sympathetic nerve activity (MSNA; microneurography) from 13 female participants in the WISE-2005 60-day HDBR study (retrospective analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13 male participants performed on data collected at baseline and during physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study, and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk between tests). Neither baseline integrated burst frequency nor incidence were altered with HDBR (both P > 0.35). However, baseline integrated burst latency increased in both HDBR studies (male: 1.35 ± 0.02 to 1.39 ± 0.02 s, P < 0.01; female: 1.23 ± 0.02 to 1.29 ± 0.02 s, P < 0.01), whereas controls exhibited no change across two visits (1.25 ± 0.02 to 1.25 ± 0.02 s, group-by-time interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03), male baseline AP data did not change with HDBR (all P > 0.19). The change in AP frequency on going from baseline to apnea (∆94 ± 25 to ∆317 ± 55 AP/min, P < 0.01) and the number of active sympathetic clusters per burst (∆0 ± 0.2 to ∆1 ± 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The change in total clusters with apnea was ∆0 ± 0.5 clusters pre- and ∆2 ± 0.7 clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified discharge characteristics in baseline burst latency and sympathetic neural recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not modify baseline sympathetic burst frequency in male and female participants, but examination of additional features of the multiunit signal provided novel evidence to suggest augmented synaptic delays or processing times at baseline for all sympathetic action potentials. Furthermore, long-duration bed rest increased reflex-sympathetic arousal to apneic stress in male participants primarily by mechanisms involving an augmented firing rate of action potential clusters active at baseline.