The Effect of Microgravity on Central Aortic Blood Pressure

It is well-known, that weightlessness during short-term spaceflights (days to few weeks) causes a shift of ~2 liters of blood and fluids from the lower body segments to the upper part of the body, that goes along with an increase of cardiac output of ~20%, despite an unchanged or decreased heart rate.1–4 The observed increase of cardiac output is thought to be due to increased venous return, i.e., an increase in cardiac preload going along with an increase of transmural central venous pressure.4 However, blood pressure either was unchanged or decreased (mainly the diastolic blood pressure) and heart rate decreased by up to 15 beats per minute during weightlessness, despite maintenance of a high sympathetic nerve activity.2–5 During long duration space flights (3 to 6 months) cardiac output and stroke volume have been shown to be increased even more by 35–41%, along with a decrease in systemic vascular resistance of 39%, despite an unchanged sympathetic nervous system (at least when assessed via measurement of plasma noradrenaline and adrenaline concentrations).6 Notwithstanding the increase of cardiac output and stroke volume, 24-h average systolic, diastolic and mean arterial pressures in space were reduced by 8, 9, and 10 mm Hg, respectively.6 Though heart rate overall was unchanged during long duration space flights, it decreased during the sleep period by 5 beats per minute, probably due to a strong parasympathetic drive during sleep.6 In addition to weightlessness studied during short-term and long duration space flights, very short-term weightlessness can be achieved during airplane flights in Keplerian trajectories also termed parabolic flights.7 Before and after achieving weightlessness for some 20 seconds, subjects are subjected to G-levels of up to 1.8. Nevertheless, parabolic flights allow to study very acute changes affected by weightlessness: the left atrium is distended abruptly, the transmural central venous pressure (this is not the central venous pressure, but takes into account intrathoracic/interpleural pressure) is increased as an indicator of increased cardiac preload, and both cardiac output and stroke volume increase considerably.4,7 Despite the increase in cardiac output and stroke volume, blood pressure is decreased by 5–12 mm Hg during this type of weightlessness, suggesting, that there must be an immediate decrease in peripheral vascular resistance due to arteriolar vasodilation. It has been speculated, that this arteriolar vasodilatation is due to a decrease of stimulation of the local myogenic vasoconstrictor responses in the lower limbs and by stimulation of the cardiopulmonary and carotid baroreflexes inducing a decrease in efferent sympathetic nerve activity to the arteriolar resistance vessels.8 This latter hypothesis has been supported by a decrease in peroneal muscle sympathetic nerve activity measured by microneurography.8 Interestingly, in addition to the factors mentioned above, spaceflight-induced changes in arterial function have been shown to happen at the level of the vessels themselves. On the one hand, it has been suggested that microgravity may result in structural changes, i.e., arterial remodeling.9 On the other hand, functional changes have been found. In order to adequately address vessel contractile function independent from humoral, metabolic, and other influences, arteries have been isolated and studied in vitro in these studies. Vessels were obtained from mice sent to space. It was observed that constriction of mouse skeletal muscle arteries evoked by different vasoconstrictor agents was reduced, while pressure-induced vasoconstriction was unaltered.10 Further, noradrenaline-induced constriction of mouse mesenteric arteries was attenuated.11 Moreover, constriction of mouse cerebral arteries induced by changes in transmural pressure, a reaction contributing considerably to cerebral blood flow autoregulation, was decreased.12 In addition, in the same vessels, the response to different vasoconstrictors (acting through different signaling pathways) was reduced and the reaction to the endothelium-dependent vasodilator acetylcholine was absent.13 Of note, all these studies employed vessels obtained from a limited number of vascular beds. Moreover, the cerebral circulation is a very specialized vascular bed. Thus, it remains to be determined whether the reported findings are representative for the circulatory system in general. All together these findings suggest that the dynamic range of vasomotor control may be attenuated in spaceflight. In the above-mentioned studies dealing with hemodynamic effects of weightlessness, blood pressure measurements were restricted to peripheral blood pressure. However, it has been known since decades, that central (aortic) blood pressure is lower than peripheral (brachial) blood pressure, and that brachial and aortic blood pressure correlate not well with each other. Evidence has been accumulating, that central blood pressure may be a better predictor for future cardiovascular morbidity and mortality than peripheral blood pressure; furthermore, differential effects of antihypertensive drugs on central versus peripheral blood pressure have been reported, i.e., betablocking agents such as atenolol and bisoprolol have been shown to exert an inferior antihypertensive effect specifically on central blood pressure when compared with angiotensin receptor blockers or calcium channel blockers.14–18 Therefore, it is of obvious interest for the scientific community to learn more on the effects of weightlessness on central blood pressure in comparison to peripheral blood pressure. It is the merit of the study by Felix Seibert et al.19 published in this issue of the American Journal of Hypertension to report the effect of microgravity (weightlessness) on central aortic blood pressure for the first time. Microgravity was achieved by 217 parabolic flight maneuvers during 7 flights with an Airbus A310 performed in Bordeaux by Novespace. Noninvasive measurement of central aortic pressure was done with the Mobil-O-Graph device via a tonometric contour analysis of the brachial arterial pulse wave. Main findings in 20 healthy subjects aged 19–43 years were an increase of central systolic blood pressure from 124 mm Hg (interquartile range [IQR] = 118–133) to 127 mm Hg (IQR = 119–133), despite a decrease of peripheral vascular resistance from 1.30 s * mm Hg/ml (IQR = 1.14–1.48) to 1.25 s * mm Hg/ml (IQR 1.15–1.40), and an increase of cardiac index from 2.5 l/min/m2 (IQR = 2.2–2.8) to 2.7 l/min/m2 (IQR = 2.3–3.0) due to a considerable increase in stroke volume given the parallel decrease of heart rate from 80 beats/min (IQR = 70–91) to 74 beats/min (IQR = 66–82). In contrast to central systolic blood pressure, peripheral systolic blood pressure was unchanged. Interestingly, direct telemetric measurement of blood pressure in mice during spaceflight showed a slight increase in blood pressure,20 supporting the findings by Seibert et al. published in this issue of the American Journal of Hypertension. Of note, in the much smaller mice, fluid redistribution during spaceflight due to changes in hydrostatic pressure conditions is much smaller compared to humans. This study by Seibert thereby adds important novel information on (i) central blood pressure regulation during microgravity, and (ii) short-term cardiovascular regulation during microgravity. However, the study results are somewhat at variance with the above trials during parabolic flight maneuvers, where peripheral blood pressure was considerably decreased during weightlessness. One possible explanation of this difference might be that participants of the present study were amateurs, but not professionally trained astronauts. Amateurs might be more excited/nervous about all the unknown procedures than professional astronauts. In this line, heart rate has continuously decreased from sets 1 to 6 of the first and second parabolic flight campaign from on average 94 beats/min to 87 beats/min and overall was lower during the second parabolic flight campaign with 80 beats/min. Similarly peripheral systolic blood pressure has continuously decreased from sets 1 to 6 of the first and second parabolic flight campaign from on average 135 mm Hg to 125 mm Hg. Nevertheless, during this second parabolic flight campaign, central systolic blood pressure increased during weightlessness. It would be of high interest to repeat these studies with professionally trained astronauts. In order to better understand the underlying mechanisms of cardiocirculatory regulation during parabolic flight maneuvers, additional information about central and peripheral blood pressure, heart rate, peripheral vascular resistance, cardiac index/stroke volume as well as augmentation index and pressure, and pulse wave velocity with regard to pull up and pull out phase with a gravity of 1.5–1.8g should be obtained or provided, if already available. For the scientific community, it is of high interest to learn more about the effects of weightlessness on central blood pressure regulation, therefore we strongly support the concept of including central blood pressure measurements on the ongoing ISS mission. It is of special interest to study long-term effects of weightlessness on central blood pressure and arterial elasticity in astronauts, since these results may have implications for cardiovascular risk estimation and choice of treatment. The authors declared no conflict of interest.