Tadaaki Mano

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

Muscle sympathetic nerve activity (MSNA) was measured directly along with blood pressure at rest in 69 healthy women (20-79 yr old) and 76 age-matched healthy men (16-80 yr old). All were nonobese and normotensive. In the women and men the MSNA was positively correlated with age (women: y = 0.788x - 5.418, r = 0.846, P < 0. 0001; men: y = 0.452x + 12.565, r = 0.751, P < 0.0001). The regression intercept of y was significantly lower (P < 0.0001) in the women than in the men, and the regression slope was significantly steeper (P < 0.0001) in the women. The MSNA was lower in women than in men among those <30 (P = 0.0012), 30-39 (P = 0. 0126), and 40-49 yr old (P = 0.0462) but was similar in women and men among those 50-59 (P = 0.1911, NS) and >/=60 yr old (P = 0.1739, NS). The results suggest that MSNA increases with age in women and men and that the activity is markedly lower in young women than in men but is markedly accelerated with age.

Responses in muscle sympathetic activity (MSA) to acute hypoxia were studied in 13 healthy male subjects under hypobaric hypoxic conditions at a simulated altitude of 4,000, 5,000, and 6,000 m. Efferent postganglionic MSA was recorded directly with a tungsten microelectrode inserted percutaneously into the tibial nerve. Heart rate (HR) and respiratory rate (RR) were counted respectively from the R wave of an electrocardiogram and from the respiratory tracing recorded by the strain-gauge method. The average values of the MSA burst rate and total activity of MSA (burst rate x mean burst amplitude) at 4,000, 5,000, and 6,000 m were 36.4 +/- 2.6, 39.1 +/- 3.1, and 40.2 +/- 4.2 (SE) bursts/min and 616 +/- 138, 794 +/- 190, and 764 +/- 227 arbitrary units, respectively. These values were significantly higher than the values of 27.1 +/- 2.9 bursts/min and 446 +/- 28 at sea level. HR increased significantly at altitudes, but RR did not show significant change. Under severe hypoxic conditions beyond 5,000 m, there were large interindividual differences in the MSA responsiveness to hypoxia. The results indicate that MSA is activated under hypoxia by stimulating the chemoreceptors. However, the central controlling mechanisms that would be affected by hypoxia may also influence the MSA responsiveness under severe hypoxia.

Muscle sympathetic nerve activity (MSA) was recorded microneurographically from the tibial nerve in 40 healthy male subjects aged 18 to 75. Passive and graded head-up tiltings were loaded on the subjects. The effects of aging on the resting activity of muscle sympathetic nerve in supine position at rest (burst number per minute), increase in MSA from the resting level by orthostasis (slope of the regression line between sine of the tilt angle and MSA bursts per minute), and the MSA in upright standing position were analyzed. The resting MSA increased with age, and a significant positive correlation was observed between age and resting activity (Y = -6.83 +/- 0.876X, r = .882, p less than .001). The MSA was enhanced by head-up tilt linearly with the sine of the tilt angle, and a significant negative correlation was observed between age and the MSA increase by orthostasis (Y = 57.6 - 0.582X, r = . 843, p less than .001). Standing MSA increased significantly but less remarkably than resting MSA. It was concluded that aging increases the resting activity, but there is less increase in the standing activity of sympathetic outflow to muscles in humans.