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24-h blood pressure in Space: The dark side of being an astronaut
Respiratory Physiology & Neurobiology 169S (2009) S55–S58
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
24-h blood pressure in Space: The dark side of being an astronaut夽 John M. Karemaker ∗ , Janneke Berecki-Gisolf Department of Systems Physiology, Academic Medical Center at the University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
a r t i c l e
i n f o
Article history: Accepted 20 May 2009 Keywords: Systemic vascular resistance Spaceflight Blood pressure ESA HDT-bed rest Microgravity Portapres Psychological stress
a b s t r a c t Inflight 24-h profiles of blood pressure (BP) and heart rate (HR) were recorded in 2 ESA-astronauts by automatic upper arm cuff measurements. In one astronaut this was combined with PortapresTM continuous finger blood pressure recordings. It was the intention to contrast the latter to 24-h recordings in an earlier Head-Down-Tilted (HDT) bed rest study [Voogel, A.J., Stok, W.J., Pretorius, P.J., Van Montfrans, G.A., Langewouters, G.J., Karemaker, J.M., 1997. Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt. Acta Physiol. Scand. 161, pp. 71–80]. BP-levels in Space were not very much changed from preflight; the circadian BP-rhythm seemed dampened. Only daytime diastolic pressures (both subjects) and nighttime HR (one subject) were significantly lower in Space. However, compared to the effect of a control tilt manoeuvre on the ground, even lower BP values might have been expected. Striking were the BP- and HR-surges during the working days in Space, often related to stressful moments like live appearances on public TV. Systemic vascular resistance (SVR) dropped during the night, unlike HDT. Thus, actual spaceflight refuted our earlier findings in HDT both for BP-levels and for daytime to nighttime changes. The combined observations lead to the hypothesis that short-lasting spaceflight may induce strong psychological stress in astronauts. When interpreting space-physiological observations this must be taken into account. © 2009 Elsevier B.V. All rights reserved.
1. Introduction In earlier studies (Fritsch-Yelle et al., 1996) the matter of how microgravity affects the circadian pattern of the cardiovascular system seems to have been settled once and for all: Blood pressure (BP) and heart rate (HR) are slightly decreased, the circadian pattern is almost unchanged. In contrast to these findings, sympathetic activity was found to be slightly increased, probably to compensate for the reduced blood volume in the circulation (animal studies by Kvetnansky et al., 1981, confirmed in human studies by, among others, Christensen et al., 2005 and in the Neurolab-mission, see below). In general, the approach of scientists to the loss of gravity in spaceflight has been to consider their subjects of study just as that: subjects more or less passively undergoing the effect of the changed gravity. This view takes only part of the story into account. It leaves aside the fact that for most astronauts “their” spaceflight is a life-event, the culmination of a long period of training after a selection procedure which lifted them from the competing crowd for their special capacities.
夽 This paper is part of a supplement entitled “Cardio-Respiratory Physiology in Space”, guest-edited by P. Norsk and D. Linnarsson. ∗ Tel.: +31 20 5664827. E-mail address: [email protected] (J.M. Karemaker). 1569-9048/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2009.05.006
This sketch may be considered a caricature, but it holds particularly true for countries like European Space Agency (ESA)-member states where chances of becoming an astronaut are low, and even when someone has made it to that level, the waiting time to get assigned to a flight can take a persons’ best years. Under these circumstances the circadian pattern of inflight blood pressure may not represent a truthful image of the effect of microgravity alone. The present study was designed to compare the circadian pattern of blood pressure and heart rate in actual spaceflight to what we had observed earlier in HDT-bed rest (Voogel et al., 1997). The initial hypothesis was that simulation and spaceflight would show the same day/night changes. HDT had shown a dampened day/night systolic pressure pattern, with almost equal diastolic pressures day and night, the same diastolic pressure as during a control night. This was combined with almost unchanged heart rate (HR) and cardiac output (CO) patterns but reversed systemic vascular resistance (SVR) pattern, nighttime-SVR being higher than during the day. We had the co-operation of 2 ESA-selected astronauts to investigate their circadian blood pressure and heart rate when they took part in Soyuz-Taxi-flights to and from the International Space Station as short-stay cosmonauts. Such a flight brings up a fresh Soyuz-module to dock to the International Space Station to serve as emergency-return module for the next period of half a year. Of the crew of 3 cosmonauts 2 remain on the ISS for the coming shift. The third crew member returns with 2 replaced ISS-crew in the ‘old’ Soyuz-module after 10 days. (Candidate-) astronauts from the ESA-
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J.M. Karemaker, J. Berecki-Gisolf / Respiratory Physiology & Neurobiology 169S (2009) S55–S58
Table 1 Subject data and experiment days in relation to launch of spaceflight. Subject
Age (y)
Height (m)
Weight (kg)
Preflight
Inflight
Postflight
A B
40 45
1.80 1.85
67 87
L-65/L-30 L-50/L-49
FD 8 FD 5/FD 8
n.a. R + 4/R + 10
corps can have the role of the third Soyuz crew member, staying on the ISS for the intervening 10-day period. This gives the member states an extra opportunity to have microgravity experiments performed on ISS. In general, this implies that the short-stay astronaut has a heavy load of experiments to be carried out in the short period on the ISS, on top of the extra training and language lessons which are required to be able to work the Russian module. We followed the circadian pattern of blood pressure and heart rate by a portable device that made automatic upper arm cuff measurements at set intervals. Additionally, in one of the 2 astronauts this was complemented with continuous blood pressure recording by the Finapres/PortapresTM technique. This would enable us to analyze beat-by-beat changes in blood pressure and heart rate during (parts of) the ‘normal’ day and night of an astronaut in Space. Moreover, by pulse contour analysis of the arterial wave form (relative) changes in stroke volume and systemic vascular resistance can be tracked (Wesseling et al., 1993). This would allow the analysis of the changes that underlie observed changes in blood pressure, in particular in the transition from day to night. 2. Test subjects and methods Two ESA-astronauts scheduled for Taxi-flights participated in this study. Subject data and recording days are given in Table 1. To protect the identity and privacy of the subjects as much as possible in this case where only 2 astronauts participated, these data must be limited. We will refrain from giving exact blood pressure levels and zoom in on the changes that were observed on the various experiment days. Therefore, we have set the average diastolic blood pressure over the nadir of 2 nights of preflight recordings as reference level 0. This is explained in Fig. 1; the nadir occurring around
4 o’clock at night. Every blood pressure data point is referenced to that level (in mmHg). Subjects participated in the experiments after written informed consent. The protocol had been approved both by the local ethics committee of the Academic Medical Center and ESA’s Medical Board. The study complies with the declaration of Helsinki. To measure the circadian blood pressure pattern an automatic upper arm cuff device was used (equipment provided by ESA: TM 2430PC BOSO -Germany and space-qualified by Kayser-Threde GmbH). This device automatically measures blood pressure and heart rate by an oscillometric method every 15 min during the waking period and every half hour during the period reserved for sleep. For continuous recording of finger pressure by the Finapres technique a space-qualified version of PortapresTM (BMI-TNO, Amsterdam, NL) was used. This instrument has been integrated by CNES (Fra) into the physiological measurement suite ‘Cardioscience System’. Portapres was programmed to switch between measuring on the middle- and ring-finger every half hour. The various modules are available onboard the ISS through ESA and CNES (the French Space Agency) for investigators. Subject B, the second astronaut who underwent recordings of upper arm cuff pressure measurement and Portapres together, could only do so at moments where the finger pressure measurement would not interfere with normal daily activities that required the use of both hands. This restricted the application of Portapres to more or less quiet moments of the day and the late evening presleep to sleep transition. When exactly Portapres would be applied was left to the discretion of the astronaut. The main problem to use the ISS-onboard Portapres in a ‘freefloating’ application rather than on a power-wire connected to the equipment was to find rechargeable batteries that would fulfill the stringent safety requirements for the ISS. NASA technical crew pointed out that the onboard MakitaTM power tools (used for drilling and screwdrivers) do have rechargeable packs that fulfill the requirements of Portapres. Therefore the 2nd astronaut carried 2 adapted Makita power tool handles to the ISS to be used with these battery packs for the planned Portapres recordings.
Fig. 1. 24-h blood pressure and heart rate recordings before and during spaceflight. All blood pressure levels are referenced to the nadir of diastolic values in the 2 nights of the preflight baseline recordings (ellipses in panels A and C). L-50 denotes 50 days before launch, FD 8 denotes flight day 8. The darkened portions indicate the sleep period. Due to logistics not all recordings are starting at the same time of the day, time scale is indicated. Symbols: ( ) denote HR values (right hand scales), () systolic pressures and () diastolic pressures. To improve readability a moving average of 4 has been applied to the various data sets.
J.M. Karemaker, J. Berecki-Gisolf / Respiratory Physiology & Neurobiology 169S (2009) S55–S58
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Table 2 Averaged circadian blood pressures and heart rates.
Fig. 2. Portapres recording inflight at the moment of ‘official’ picture taking during a meal (actual photo moment marked by up arrow). Probably due to movements the Portapres signal had become unstable, as evidenced by the repeated ‘staircases’ in the recording where the Physiocal© mechanism cuts in to check volume clamp conditions required for a stable recording (cf. Imholz et al., 1998).
3. Results As implied in this study, the obtained results must be seen as ‘anecdotal’ since only 2 subjects participated. Subject A was on his second spaceflight, he had earlier experience on the Shuttle, subject B was a Space-novice. As shown in Fig. 1A already the preflight circadian pattern of BP and HR in subject A had only a clear-cut increase and some variability in HR during daytime, BP-day/night pattern was not very conspicuous. The inflight pattern was even less outspoken (Fig. 1B), almost no clear day/night pattern in diastolic BP, only some BP increases related to work at the ISS, HR being as ‘reactive’ in Space as it was on the ground. Fig. 1C/D shows for subject B that his baseline BP-increase of around 20 mmHg during daytime had become much more variable during the working day in Space, mostly situational related. For some of these data points we had concurrent Portapres recordings, which documented this instantaneous impact as shown in Fig. 2 where pictures were taken during mealtime. Remarkable were the increases in BP and HR during a live TV-interview with officials from his home state. Since the values in Fig. 1 are smoothed with a moving average of 4 adjacent points to increase readability these extremes are not readily observed in the pictures. However, the distribution width of daytime inflight systolic pressure values had doubled compared to preflight as an expression of this variability. Sleeping HR was remarkable in subject B: inflight it dropped to values around 50 bpm which he did not have on the ground, neither before nor after spaceflight. The results of the wake-to-sleep Portapres-recordings refuted the earlier HDT-observations. Preflight we observed a conspicuous drop in systemic vascular resistance on falling asleep (to 65% of awake in the first half hour). Inflight this was less: a drop to 85% in the first half hour. This picture was mirrored by increases in stroke volume during sleep: +55% preflight to +20% inflight. In view of a peculiarity of Portapres we have to restrict our comparisons to the first half hour of the sleeping period, even though more data are available. Fig. 3 shows how the blood pressure tracing jumped by some 20 mmHg when the recording site changed from one finger to the other every 30 min. This did not occur in all recordings, but it spoiled this one good Portapres sleep recording that we obtained
Fig. 3. Portapres recording inflight during the first hours of sleep (flight day 10, additional recording). This 3.5 h recording shows a peculiarity of the automatic finger-switching feature of Portapres: after 30 min running on the middle finger automatically the measurement switches to the adjacent cuff on the ring finger and vice versa. However, the set point algorithm finds and maintains different pressure levels in the two fingers, resulting in spurious pressure jumps every half hour.
Subject
Parameter
Preflight
Inflight
Postflight
Day
Night
Day
Night
Day
Night
A
Systolic (ref) Diastolic (ref) HR
58.8 15.0 65.2
43.3 2.3 51.6
55.7 4.9* 67.9
42.2 −1.0 50.6
n.a. n.a. n.a.
n.a. n.a. n.a.
B
Systolic (ref) Diastolic (ref) HR
78.2 22.1 81.9
52.5 3.2 65.2
74.1 13.9* 75.1*
50.4 8.0 56.1*
81.4 19.2 87.7*
60.3 8.6 69.9
Systolic and diastolic pressures (in mmHg) are referenced to the preflight diastolic nightly trough, as indicated in the text. HR is in beats/min. Significances are signalled by * and bold type in comparison to preflight values. A value is considered significantly different when outside the range of the preflight value +/− 3 × SEM; n.a. = not applicable; this astronaut was not available for postflight measurements.
in Space, earlier recordings having failed due to various technical reasons. Table 2 presents a condensed overview of all measurements of circadian BP and HR in both astronauts, pre-, in- and postflight, respective values taken together as appropriate. It substantiates the impression given by Fig. 1 that, indeed, there are subtle changes in the circadian pattern of BP and HR inflight compared to preflight. Values were considered significantly different when they were outside the range of preflight value +/− 3 × SEM. In view of the low number of subjects (and few repetitions of the recordings) this seemed a reasonable compromise. Daytime inflight diastolic pressures are significantly lower than preflight in both astronauts. HR values in subject B are inflight significantly lower, day and night, and significantly higher during daytime postflight. 4. Discussion The heart is a mirror of the soul. That is one of the reasons why physiologists and psychologists alike have such interest in heart rate and blood pressure since they are supposed to tell the underlying story of the (autonomic) nervous system. In this study we have followed astronauts in their daily activities with portable blood pressure recording devices. In view of the Space-conditions it is not easy to virtually block the use of one hand for measurement by the Portapres technique. In microgravity hands are the best instruments for propulsion and steering, legs having almost no function. This fact limits the occasions where Portapres can be used without too much hindering the normal activities of the crewmember. And even then it is almost impossible to prevent artifacts due to bending the fingers or bumping into objects or the surrounding walls. In view of the absence of gravity, it was to be expected that BP and HR would mainly be determined by physical activity and psychological status. An earlier study in 12 male astronauts (FritschYelle et al., 1996) had documented subtle changes in circadian patterns of BP and HR, comparable to what we observed here. Both astronauts showed decreased diastolic pressures during the day. Here the question arises if the preflight circadian pattern should be considered the gold standard for spaceflight comparison. Usually BP is referenced to heart level, daytime BP is mainly upright BP. In that posture a hydrostatic pressure difference exists between the carotid sinuses and the heart. As a consequence, the carotid sinuses will signal a lowered pressure (by some 20 mmHg) after a rise from supine. In the upright posture this will add to the up regulation of BP at heart level. Therefore, it is more appropriate to compare the condition in Space to the awake, supine BP on the ground when all hydrostatic effects are minimized. Since both astronauts had taken part in yet another experiment in our laboratory, we do have preflight tilttable recordings in both. In the head-up tilt test of subject A we observed no change in systolic pressure and an increase of diastolic pressure by 11 mmHg; subject B showed and increase of 17 mmHg
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of both, systolic and diastolic pressures. Upright HR increased by 26 bpm in A and by 18 bpm in B. This makes the observed drop in diastolic BP in subject A (10 mmHg, Table 2) a value to be expected, and the drop in subject B (8 mmHg) even less than expected. The same holds true for inflight daytime HR, which dropped less in B than to be expected from the tilt test and it did not change at all in A. The reports of the Neurolab-mission in 1998 (Cox et al., 2002; Ertl et al., 2002; Eckberg, 2003) have documented an increase in sympathetic nervous system activity in Space for the first time by direct measurement of neural efferent traffic in man. This was explained as adaptation to the condition of hypovolemia. In the present study indications of systematically increased sympathetic activity are only indirect. As argued above, in subject B the inflight daytime values for BP and HR are higher than to be expected and in A only HR was higher. Additionally, in both astronauts inflight daytime values are more variable than on the ground, situationally determined. Recovery period measurements were only possible in subject B, since he had been assigned to stay in Star-city for follow-up measurements; subject A was not available to us postflight. As shown in Table 2, postflight BP values show a tendency to be higher than preflight and definitely so for HR. A long recovery period after short spaceflight has been observed before (Migeotte et al., 2003). This has been confirmed in a study by Verheyden et al., 2007, who followed cardiovascular reflexes among others in the same test subjects as we did. They showed that it took at least 25 days postflight for these reflex responses to return to preflight levels. The inflight changes that we had expected from our earlier HDTexperience at first seemed to materialize in subject A, but only as far as his pattern of diastolic pressures was concerned. The daytime stresses in actual spaceflight probably make for more arousal than is experienced during HDT bed rest. Subject B’s Portapres recordings did not show the expected reversal of SVR-pattern: nighttime-SVR higher than daytime in HDT, lower in Space. However, subject B already had a very outspoken SVR-pattern preflight, which was different from what we had found in our 7 HDT-test subjects. In conclusion, we have shown the feasibility of extensive inflight cardiovascular measurements, even in busy astronauts, while they are performing many of their normal duties. From these observations we have learned to take the psychological aspects of spaceflight more into account when judging the adaptation to microgravity. The waking blood pressure and heart rate values are determined both by the psychology and the physiology of the weightless condition. Our earlier findings in HDT have not been confirmed.
Acknowledgments This study was supported by the Dutch Space Research Organization Netherlands (SRON) by several grants. We are very grateful to the ESA-test subjects, i.e. the astronauts and their back-ups who cordially took part and helped at various moments in these studies. The help by ESA, NASA, CNES, Medes and IBMP is gratefully acknowledged. We mention in particular the BMI-TNO crew who helped us out on many occasions and the representative of the Dutch Department of Economic Affairs who eased our way through international diplomacy. The authors are indebted to their co-workers who helped to carry out these experiments. The interpretation given in this paper is entirely their own and need not necessarily represent the views of Wim J. Stok and Gert A. van Montfrans. References Christensen, N.J., Heer, M., Ivanova, K., Norsk, P., 2005. Sympathetic nervous activity decreases during head-down bed rest but not during microgravity. J. Appl. Physiol. 99, 1552–1557. Cox, J.F., Tahvanainen, K.U., Kuusela, T.A., Levine, B.D., Cooke, W.H., Mano, T., Iwase, S., Saito, M., Sugiyama, Y., Ertl, A.C., Biaggioni, I., Diedrich, A., Robertson, R.M., Zuckerman, J.H., Lane, L.D., Ray, C.A., White, R.J., Pawelczyk, J.A., Buckey Jr., J.C., Baisch, F.J., Blomqvist, C.G., Robertson, D., Eckberg, D.L., 2002. Influence of microgravity on astronauts’ sympathetic and vagal responses to Valsalva’s manoeuvre. J. Physiol. 538, 309–320. Eckberg, D.L., (for the Neurolab Autonomic Nervous System Team), 2003. Bursting into space: alterations of sympathetic control by space travel. Acta Physiol. Scand. 177, 299–311. Ertl, A.C., Diedrich, A., Biaggioni, I., Levine, B.D., Robertson, R.M., Cox, J.F., Zuckerman, J.H., Pawelczyk, J.A., Ray, C.A., Buckey Jr., J.C., Lane, L.D., Shiavi, R., Gaffney, F.A., Costa, F., Holt, C., Blomqvist, C.G., Eckberg, D.L., Baisch, F.J., Robertson, D., 2002. Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. J. Physiol. 538, 321–329. Fritsch-Yelle, J.M., Charles, J.B., Jones, M.M., Wood, M.L., 1996. Microgravity decreases heart rate and arterial pressure in humans. J. Appl. Physiol. 80, 910–914. Imholz, B.P., Wieling, W., van Montfrans, G.A., Wesseling, K.H., 1998. Fifteen years experience with finger arterial pressure monitoring: assessment of the technology. Cardiovasc. Res. 38, 605–616, Review. Kvetnansky, R., Vigas, M., Tigranyan, R.A., Nemeth, S., Macho, L., 1981. Activity of the sympathetic-adrenomedullary system in rats after space flight on the Cosmos biosatellites. Adv. Space Res. 14, 187–192. Migeotte, P.F., Prisk, G.K., Paiva, M., 2003. Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans. Am. J. Physiol. Heart Circ. Physiol. 284, H1995–2006. Verheyden, B., Beckers, F., Couckuyt, K., Liu, J., Aubert, A.E., 2007. Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight. Acta Physiol. (Oxf.). 191, 297–308. Voogel, A.J., Stok, W.J., Pretorius, P.J., Van Montfrans, G.A., Langewouters, G.J., Karemaker, J.M., 1997. Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt. Acta Physiol. Scand. 161, 71–80. Wesseling, K.H., Jansen, J.R.C., Settels, J.J., Schreuder, J.J., 1993. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J. Appl. Physiol. 74, 2566–2573.
Contents lists available at ScienceDirect
Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol
24-h blood pressure in Space: The dark side of being an astronaut夽 John M. Karemaker ∗ , Janneke Berecki-Gisolf Department of Systems Physiology, Academic Medical Center at the University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
a r t i c l e
i n f o
Article history: Accepted 20 May 2009 Keywords: Systemic vascular resistance Spaceflight Blood pressure ESA HDT-bed rest Microgravity Portapres Psychological stress
a b s t r a c t Inflight 24-h profiles of blood pressure (BP) and heart rate (HR) were recorded in 2 ESA-astronauts by automatic upper arm cuff measurements. In one astronaut this was combined with PortapresTM continuous finger blood pressure recordings. It was the intention to contrast the latter to 24-h recordings in an earlier Head-Down-Tilted (HDT) bed rest study [Voogel, A.J., Stok, W.J., Pretorius, P.J., Van Montfrans, G.A., Langewouters, G.J., Karemaker, J.M., 1997. Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt. Acta Physiol. Scand. 161, pp. 71–80]. BP-levels in Space were not very much changed from preflight; the circadian BP-rhythm seemed dampened. Only daytime diastolic pressures (both subjects) and nighttime HR (one subject) were significantly lower in Space. However, compared to the effect of a control tilt manoeuvre on the ground, even lower BP values might have been expected. Striking were the BP- and HR-surges during the working days in Space, often related to stressful moments like live appearances on public TV. Systemic vascular resistance (SVR) dropped during the night, unlike HDT. Thus, actual spaceflight refuted our earlier findings in HDT both for BP-levels and for daytime to nighttime changes. The combined observations lead to the hypothesis that short-lasting spaceflight may induce strong psychological stress in astronauts. When interpreting space-physiological observations this must be taken into account. © 2009 Elsevier B.V. All rights reserved.
1. Introduction In earlier studies (Fritsch-Yelle et al., 1996) the matter of how microgravity affects the circadian pattern of the cardiovascular system seems to have been settled once and for all: Blood pressure (BP) and heart rate (HR) are slightly decreased, the circadian pattern is almost unchanged. In contrast to these findings, sympathetic activity was found to be slightly increased, probably to compensate for the reduced blood volume in the circulation (animal studies by Kvetnansky et al., 1981, confirmed in human studies by, among others, Christensen et al., 2005 and in the Neurolab-mission, see below). In general, the approach of scientists to the loss of gravity in spaceflight has been to consider their subjects of study just as that: subjects more or less passively undergoing the effect of the changed gravity. This view takes only part of the story into account. It leaves aside the fact that for most astronauts “their” spaceflight is a life-event, the culmination of a long period of training after a selection procedure which lifted them from the competing crowd for their special capacities.
夽 This paper is part of a supplement entitled “Cardio-Respiratory Physiology in Space”, guest-edited by P. Norsk and D. Linnarsson. ∗ Tel.: +31 20 5664827. E-mail address: [email protected] (J.M. Karemaker). 1569-9048/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2009.05.006
This sketch may be considered a caricature, but it holds particularly true for countries like European Space Agency (ESA)-member states where chances of becoming an astronaut are low, and even when someone has made it to that level, the waiting time to get assigned to a flight can take a persons’ best years. Under these circumstances the circadian pattern of inflight blood pressure may not represent a truthful image of the effect of microgravity alone. The present study was designed to compare the circadian pattern of blood pressure and heart rate in actual spaceflight to what we had observed earlier in HDT-bed rest (Voogel et al., 1997). The initial hypothesis was that simulation and spaceflight would show the same day/night changes. HDT had shown a dampened day/night systolic pressure pattern, with almost equal diastolic pressures day and night, the same diastolic pressure as during a control night. This was combined with almost unchanged heart rate (HR) and cardiac output (CO) patterns but reversed systemic vascular resistance (SVR) pattern, nighttime-SVR being higher than during the day. We had the co-operation of 2 ESA-selected astronauts to investigate their circadian blood pressure and heart rate when they took part in Soyuz-Taxi-flights to and from the International Space Station as short-stay cosmonauts. Such a flight brings up a fresh Soyuz-module to dock to the International Space Station to serve as emergency-return module for the next period of half a year. Of the crew of 3 cosmonauts 2 remain on the ISS for the coming shift. The third crew member returns with 2 replaced ISS-crew in the ‘old’ Soyuz-module after 10 days. (Candidate-) astronauts from the ESA-
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J.M. Karemaker, J. Berecki-Gisolf / Respiratory Physiology & Neurobiology 169S (2009) S55–S58
Table 1 Subject data and experiment days in relation to launch of spaceflight. Subject
Age (y)
Height (m)
Weight (kg)
Preflight
Inflight
Postflight
A B
40 45
1.80 1.85
67 87
L-65/L-30 L-50/L-49
FD 8 FD 5/FD 8
n.a. R + 4/R + 10
corps can have the role of the third Soyuz crew member, staying on the ISS for the intervening 10-day period. This gives the member states an extra opportunity to have microgravity experiments performed on ISS. In general, this implies that the short-stay astronaut has a heavy load of experiments to be carried out in the short period on the ISS, on top of the extra training and language lessons which are required to be able to work the Russian module. We followed the circadian pattern of blood pressure and heart rate by a portable device that made automatic upper arm cuff measurements at set intervals. Additionally, in one of the 2 astronauts this was complemented with continuous blood pressure recording by the Finapres/PortapresTM technique. This would enable us to analyze beat-by-beat changes in blood pressure and heart rate during (parts of) the ‘normal’ day and night of an astronaut in Space. Moreover, by pulse contour analysis of the arterial wave form (relative) changes in stroke volume and systemic vascular resistance can be tracked (Wesseling et al., 1993). This would allow the analysis of the changes that underlie observed changes in blood pressure, in particular in the transition from day to night. 2. Test subjects and methods Two ESA-astronauts scheduled for Taxi-flights participated in this study. Subject data and recording days are given in Table 1. To protect the identity and privacy of the subjects as much as possible in this case where only 2 astronauts participated, these data must be limited. We will refrain from giving exact blood pressure levels and zoom in on the changes that were observed on the various experiment days. Therefore, we have set the average diastolic blood pressure over the nadir of 2 nights of preflight recordings as reference level 0. This is explained in Fig. 1; the nadir occurring around
4 o’clock at night. Every blood pressure data point is referenced to that level (in mmHg). Subjects participated in the experiments after written informed consent. The protocol had been approved both by the local ethics committee of the Academic Medical Center and ESA’s Medical Board. The study complies with the declaration of Helsinki. To measure the circadian blood pressure pattern an automatic upper arm cuff device was used (equipment provided by ESA: TM 2430PC BOSO -Germany and space-qualified by Kayser-Threde GmbH). This device automatically measures blood pressure and heart rate by an oscillometric method every 15 min during the waking period and every half hour during the period reserved for sleep. For continuous recording of finger pressure by the Finapres technique a space-qualified version of PortapresTM (BMI-TNO, Amsterdam, NL) was used. This instrument has been integrated by CNES (Fra) into the physiological measurement suite ‘Cardioscience System’. Portapres was programmed to switch between measuring on the middle- and ring-finger every half hour. The various modules are available onboard the ISS through ESA and CNES (the French Space Agency) for investigators. Subject B, the second astronaut who underwent recordings of upper arm cuff pressure measurement and Portapres together, could only do so at moments where the finger pressure measurement would not interfere with normal daily activities that required the use of both hands. This restricted the application of Portapres to more or less quiet moments of the day and the late evening presleep to sleep transition. When exactly Portapres would be applied was left to the discretion of the astronaut. The main problem to use the ISS-onboard Portapres in a ‘freefloating’ application rather than on a power-wire connected to the equipment was to find rechargeable batteries that would fulfill the stringent safety requirements for the ISS. NASA technical crew pointed out that the onboard MakitaTM power tools (used for drilling and screwdrivers) do have rechargeable packs that fulfill the requirements of Portapres. Therefore the 2nd astronaut carried 2 adapted Makita power tool handles to the ISS to be used with these battery packs for the planned Portapres recordings.
Fig. 1. 24-h blood pressure and heart rate recordings before and during spaceflight. All blood pressure levels are referenced to the nadir of diastolic values in the 2 nights of the preflight baseline recordings (ellipses in panels A and C). L-50 denotes 50 days before launch, FD 8 denotes flight day 8. The darkened portions indicate the sleep period. Due to logistics not all recordings are starting at the same time of the day, time scale is indicated. Symbols: ( ) denote HR values (right hand scales), () systolic pressures and () diastolic pressures. To improve readability a moving average of 4 has been applied to the various data sets.
J.M. Karemaker, J. Berecki-Gisolf / Respiratory Physiology & Neurobiology 169S (2009) S55–S58
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Table 2 Averaged circadian blood pressures and heart rates.
Fig. 2. Portapres recording inflight at the moment of ‘official’ picture taking during a meal (actual photo moment marked by up arrow). Probably due to movements the Portapres signal had become unstable, as evidenced by the repeated ‘staircases’ in the recording where the Physiocal© mechanism cuts in to check volume clamp conditions required for a stable recording (cf. Imholz et al., 1998).
3. Results As implied in this study, the obtained results must be seen as ‘anecdotal’ since only 2 subjects participated. Subject A was on his second spaceflight, he had earlier experience on the Shuttle, subject B was a Space-novice. As shown in Fig. 1A already the preflight circadian pattern of BP and HR in subject A had only a clear-cut increase and some variability in HR during daytime, BP-day/night pattern was not very conspicuous. The inflight pattern was even less outspoken (Fig. 1B), almost no clear day/night pattern in diastolic BP, only some BP increases related to work at the ISS, HR being as ‘reactive’ in Space as it was on the ground. Fig. 1C/D shows for subject B that his baseline BP-increase of around 20 mmHg during daytime had become much more variable during the working day in Space, mostly situational related. For some of these data points we had concurrent Portapres recordings, which documented this instantaneous impact as shown in Fig. 2 where pictures were taken during mealtime. Remarkable were the increases in BP and HR during a live TV-interview with officials from his home state. Since the values in Fig. 1 are smoothed with a moving average of 4 adjacent points to increase readability these extremes are not readily observed in the pictures. However, the distribution width of daytime inflight systolic pressure values had doubled compared to preflight as an expression of this variability. Sleeping HR was remarkable in subject B: inflight it dropped to values around 50 bpm which he did not have on the ground, neither before nor after spaceflight. The results of the wake-to-sleep Portapres-recordings refuted the earlier HDT-observations. Preflight we observed a conspicuous drop in systemic vascular resistance on falling asleep (to 65% of awake in the first half hour). Inflight this was less: a drop to 85% in the first half hour. This picture was mirrored by increases in stroke volume during sleep: +55% preflight to +20% inflight. In view of a peculiarity of Portapres we have to restrict our comparisons to the first half hour of the sleeping period, even though more data are available. Fig. 3 shows how the blood pressure tracing jumped by some 20 mmHg when the recording site changed from one finger to the other every 30 min. This did not occur in all recordings, but it spoiled this one good Portapres sleep recording that we obtained
Fig. 3. Portapres recording inflight during the first hours of sleep (flight day 10, additional recording). This 3.5 h recording shows a peculiarity of the automatic finger-switching feature of Portapres: after 30 min running on the middle finger automatically the measurement switches to the adjacent cuff on the ring finger and vice versa. However, the set point algorithm finds and maintains different pressure levels in the two fingers, resulting in spurious pressure jumps every half hour.
Subject
Parameter
Preflight
Inflight
Postflight
Day
Night
Day
Night
Day
Night
A
Systolic (ref) Diastolic (ref) HR
58.8 15.0 65.2
43.3 2.3 51.6
55.7 4.9* 67.9
42.2 −1.0 50.6
n.a. n.a. n.a.
n.a. n.a. n.a.
B
Systolic (ref) Diastolic (ref) HR
78.2 22.1 81.9
52.5 3.2 65.2
74.1 13.9* 75.1*
50.4 8.0 56.1*
81.4 19.2 87.7*
60.3 8.6 69.9
Systolic and diastolic pressures (in mmHg) are referenced to the preflight diastolic nightly trough, as indicated in the text. HR is in beats/min. Significances are signalled by * and bold type in comparison to preflight values. A value is considered significantly different when outside the range of the preflight value +/− 3 × SEM; n.a. = not applicable; this astronaut was not available for postflight measurements.
in Space, earlier recordings having failed due to various technical reasons. Table 2 presents a condensed overview of all measurements of circadian BP and HR in both astronauts, pre-, in- and postflight, respective values taken together as appropriate. It substantiates the impression given by Fig. 1 that, indeed, there are subtle changes in the circadian pattern of BP and HR inflight compared to preflight. Values were considered significantly different when they were outside the range of preflight value +/− 3 × SEM. In view of the low number of subjects (and few repetitions of the recordings) this seemed a reasonable compromise. Daytime inflight diastolic pressures are significantly lower than preflight in both astronauts. HR values in subject B are inflight significantly lower, day and night, and significantly higher during daytime postflight. 4. Discussion The heart is a mirror of the soul. That is one of the reasons why physiologists and psychologists alike have such interest in heart rate and blood pressure since they are supposed to tell the underlying story of the (autonomic) nervous system. In this study we have followed astronauts in their daily activities with portable blood pressure recording devices. In view of the Space-conditions it is not easy to virtually block the use of one hand for measurement by the Portapres technique. In microgravity hands are the best instruments for propulsion and steering, legs having almost no function. This fact limits the occasions where Portapres can be used without too much hindering the normal activities of the crewmember. And even then it is almost impossible to prevent artifacts due to bending the fingers or bumping into objects or the surrounding walls. In view of the absence of gravity, it was to be expected that BP and HR would mainly be determined by physical activity and psychological status. An earlier study in 12 male astronauts (FritschYelle et al., 1996) had documented subtle changes in circadian patterns of BP and HR, comparable to what we observed here. Both astronauts showed decreased diastolic pressures during the day. Here the question arises if the preflight circadian pattern should be considered the gold standard for spaceflight comparison. Usually BP is referenced to heart level, daytime BP is mainly upright BP. In that posture a hydrostatic pressure difference exists between the carotid sinuses and the heart. As a consequence, the carotid sinuses will signal a lowered pressure (by some 20 mmHg) after a rise from supine. In the upright posture this will add to the up regulation of BP at heart level. Therefore, it is more appropriate to compare the condition in Space to the awake, supine BP on the ground when all hydrostatic effects are minimized. Since both astronauts had taken part in yet another experiment in our laboratory, we do have preflight tilttable recordings in both. In the head-up tilt test of subject A we observed no change in systolic pressure and an increase of diastolic pressure by 11 mmHg; subject B showed and increase of 17 mmHg
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of both, systolic and diastolic pressures. Upright HR increased by 26 bpm in A and by 18 bpm in B. This makes the observed drop in diastolic BP in subject A (10 mmHg, Table 2) a value to be expected, and the drop in subject B (8 mmHg) even less than expected. The same holds true for inflight daytime HR, which dropped less in B than to be expected from the tilt test and it did not change at all in A. The reports of the Neurolab-mission in 1998 (Cox et al., 2002; Ertl et al., 2002; Eckberg, 2003) have documented an increase in sympathetic nervous system activity in Space for the first time by direct measurement of neural efferent traffic in man. This was explained as adaptation to the condition of hypovolemia. In the present study indications of systematically increased sympathetic activity are only indirect. As argued above, in subject B the inflight daytime values for BP and HR are higher than to be expected and in A only HR was higher. Additionally, in both astronauts inflight daytime values are more variable than on the ground, situationally determined. Recovery period measurements were only possible in subject B, since he had been assigned to stay in Star-city for follow-up measurements; subject A was not available to us postflight. As shown in Table 2, postflight BP values show a tendency to be higher than preflight and definitely so for HR. A long recovery period after short spaceflight has been observed before (Migeotte et al., 2003). This has been confirmed in a study by Verheyden et al., 2007, who followed cardiovascular reflexes among others in the same test subjects as we did. They showed that it took at least 25 days postflight for these reflex responses to return to preflight levels. The inflight changes that we had expected from our earlier HDTexperience at first seemed to materialize in subject A, but only as far as his pattern of diastolic pressures was concerned. The daytime stresses in actual spaceflight probably make for more arousal than is experienced during HDT bed rest. Subject B’s Portapres recordings did not show the expected reversal of SVR-pattern: nighttime-SVR higher than daytime in HDT, lower in Space. However, subject B already had a very outspoken SVR-pattern preflight, which was different from what we had found in our 7 HDT-test subjects. In conclusion, we have shown the feasibility of extensive inflight cardiovascular measurements, even in busy astronauts, while they are performing many of their normal duties. From these observations we have learned to take the psychological aspects of spaceflight more into account when judging the adaptation to microgravity. The waking blood pressure and heart rate values are determined both by the psychology and the physiology of the weightless condition. Our earlier findings in HDT have not been confirmed.
Acknowledgments This study was supported by the Dutch Space Research Organization Netherlands (SRON) by several grants. We are very grateful to the ESA-test subjects, i.e. the astronauts and their back-ups who cordially took part and helped at various moments in these studies. The help by ESA, NASA, CNES, Medes and IBMP is gratefully acknowledged. We mention in particular the BMI-TNO crew who helped us out on many occasions and the representative of the Dutch Department of Economic Affairs who eased our way through international diplomacy. The authors are indebted to their co-workers who helped to carry out these experiments. The interpretation given in this paper is entirely their own and need not necessarily represent the views of Wim J. Stok and Gert A. van Montfrans. References Christensen, N.J., Heer, M., Ivanova, K., Norsk, P., 2005. Sympathetic nervous activity decreases during head-down bed rest but not during microgravity. J. Appl. Physiol. 99, 1552–1557. Cox, J.F., Tahvanainen, K.U., Kuusela, T.A., Levine, B.D., Cooke, W.H., Mano, T., Iwase, S., Saito, M., Sugiyama, Y., Ertl, A.C., Biaggioni, I., Diedrich, A., Robertson, R.M., Zuckerman, J.H., Lane, L.D., Ray, C.A., White, R.J., Pawelczyk, J.A., Buckey Jr., J.C., Baisch, F.J., Blomqvist, C.G., Robertson, D., Eckberg, D.L., 2002. Influence of microgravity on astronauts’ sympathetic and vagal responses to Valsalva’s manoeuvre. J. Physiol. 538, 309–320. Eckberg, D.L., (for the Neurolab Autonomic Nervous System Team), 2003. Bursting into space: alterations of sympathetic control by space travel. Acta Physiol. Scand. 177, 299–311. Ertl, A.C., Diedrich, A., Biaggioni, I., Levine, B.D., Robertson, R.M., Cox, J.F., Zuckerman, J.H., Pawelczyk, J.A., Ray, C.A., Buckey Jr., J.C., Lane, L.D., Shiavi, R., Gaffney, F.A., Costa, F., Holt, C., Blomqvist, C.G., Eckberg, D.L., Baisch, F.J., Robertson, D., 2002. Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. J. Physiol. 538, 321–329. Fritsch-Yelle, J.M., Charles, J.B., Jones, M.M., Wood, M.L., 1996. Microgravity decreases heart rate and arterial pressure in humans. J. Appl. Physiol. 80, 910–914. Imholz, B.P., Wieling, W., van Montfrans, G.A., Wesseling, K.H., 1998. Fifteen years experience with finger arterial pressure monitoring: assessment of the technology. Cardiovasc. Res. 38, 605–616, Review. Kvetnansky, R., Vigas, M., Tigranyan, R.A., Nemeth, S., Macho, L., 1981. Activity of the sympathetic-adrenomedullary system in rats after space flight on the Cosmos biosatellites. Adv. Space Res. 14, 187–192. Migeotte, P.F., Prisk, G.K., Paiva, M., 2003. Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans. Am. J. Physiol. Heart Circ. Physiol. 284, H1995–2006. Verheyden, B., Beckers, F., Couckuyt, K., Liu, J., Aubert, A.E., 2007. Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight. Acta Physiol. (Oxf.). 191, 297–308. Voogel, A.J., Stok, W.J., Pretorius, P.J., Van Montfrans, G.A., Langewouters, G.J., Karemaker, J.M., 1997. Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt. Acta Physiol. Scand. 161, 71–80. Wesseling, K.H., Jansen, J.R.C., Settels, J.J., Schreuder, J.J., 1993. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J. Appl. Physiol. 74, 2566–2573.