any bio students doing Summer Fellowships??

This article might be of interest to you. It's an informal synopsis I turned in for a physiology course.

Article: Cox, J.F., et al. (2002) Influence of microgravity on astronauts’ sympathetic and vagal responses to Valsalva’s manoeuvre. Journal of Physiology 538.1, pp. 309-320

What is the significance of this study?

As part of a group of three studies, this research is the first to report direct recordings of human muscle sympathetic nerve activity and noradrenaline kinetics in space. After space travel, subjects were tilted upright and their muscle sympathetic nerve activity was directly recorded.

Background

Astronauts do not have impaired function in space. However, upon returning to Earth they experience intolerance such as tachycardia, hypotension and presyncope (Buckey et al. 1996 as cited by Cox et al.). This study on the Neurolab mission focused on autonomic transients provoked by the Valsalva maneuver.

Hypothesis

Exposure to microgravity impairs sympathetic muscle and vagal-cardiac baroreflexes.

Results

Valsalva straining triggers a greater increase in muscle sympathetic nerve activity in microgravity, and the stimulus, falling arterial pressure, is also greater. This causes for the reflex gain, which is defined as the sympathetic response as a function of diastolic pressure reduction, to be normal. In summary, microgravity yields different affects on the baroreflexes. While the vagal baroreflexes are impaired, sympathetic baroreflexes are unaffected.

Discussion

What are the physiological changes in microgravity?

Studies have observed that plasma volume decreases in space, with the depression of volume being most significant on the first day of exposure. Left ventricular dimensions are found to be less in space than on Earth (Charles et al. 1994 as cited by Cox et al.) This led Cox et al. to believe that the carotid artery and aorta should have been affected in the same way. If this were the case, the function of baroreceptors in these structures may be compromised, thus leading to an altered baroreflex response.

What is the influence of microgravity on arterial baroreflexes?

While Cox et al. admit to lacking similar statistical power, they cite a study that proves that vagal baroreflex responses are impaired by microgravity. Fritsch & Eckberg measured that the range, maximum gain and operational point of sigmoid carotid distending pressure-R-R interval response relations were all lower in space. The Neurolab mission established results that concurred (R-R interval fluxes were smaller in space).

However, the two studies differ in their conclusions about space’s effect on the sympathetic baroreflexes. Fritsch & Eckberg argued that sympathetic baroreflexes would be affected, but the Neurolab mission offers contrasting results. The Neurolab mission found that responses to Valsalva straining is greater in space, but that the arterial pressure changes that stimulated this response is also greater. Thus, sympathetic gain should have occurred, and was not abnormal.

What are the potential physiological mechanisms that mediate these changes?

Blood volume is a modulator of the autonomic response to Valsalva straining. Hypovolemia in space induces a decrease in arterial pressure and in increase in muscle sympathetic activity during Valsalva straining. Chronic blood volume reductions after prolonged head-down bed rest induced similar results, but not to a lesser degree for arterial pressure and muscle sympathetic activity.

It is possible that cardiac receptors may be involved in mediating these changes. Strong evidence points to the involvement of arterial baroreceptors. If a sinoaortic denervation procedure is performed, leaving cardiac efferent and afferent neural pathways intact, then the vasoconstriction and heart rate responses disappear (Blombery & Korner 1982 as cited by Cox et al.).

It may appear that there are no baroreceptor changes in microgravity, since there is no change in baseline arterial pressure and R-R intervals. However, there are other documented studies where a stimulus should have caused change in arterial pressure, but did not such as creating a major reduction in thoracic aorta dimensions. Rather, the case is that hypovolemia causes an increase in sympathetic response, which would maintain arterial pressure. This can only be measured by direct recording of sympathetic nerve activity (baroreceptive artery dimensions).

Exercise may also play a role in mediating physiological changes. Exercise, plasma volume and autonomic function are interrelated. Exercise increases plasma volume, and during head down bed rest can restore vagal baroreflex function (Convertino et al. 1992 as cited by Cox et al.).

Cardiac atrophy has been shown to reduce left ventricular dimensions more so than hypovolemia does. In this case, cardiac receptors may be affected which may affect the regulation of these receptors by the sympathetic nervous system.

It has been established that healthy adults operate near the middle of the linear region of the vagal sigmoid arterial pressure-R-R interval relations (Rea & Eckberg 1987 as cited by Cox et al.). In addition, healthy adults also operate close to the threshold region of their reverse noradrenaline spillover. In space, astronauts do not operate under these conditions, and it may be a contributing factor that impedes the vagal baroreflex response.

Astronauts undergo chronic hypovolemia and have a decreased input from autonomic sensors. This would shift the reverse sigmoid arterial pressure-muscle sympathetic nerve activity relations. Note that the shift may begin near the astronaut’s threshold. Thus, changes in baroreceptor input caused by Valsalva maneuver may not bring them past the linear range. This would cause for the sympathetic baroreflex gain to also remain unchanged. However, the shift in the operating position on the vagal arterial pressure-R-R interval relation brings an astronaut closer to threshold. This would cause for Valsalva straining to induce a smaller reduction of R-R intervals in space than on Earth, due to reductions in baroreceptor input.

References
Blomberry, P. A. & Korner, P. I. (1982). Role of aortic and carotid sinus baroreceptors on Valsalva-like vasoconstrictor and heart rate reflexes in the conscious rabbit. Journal of the Autonomic Nervous System 5, 303–315.

Buckey, J. C., et al. (1996). Orthostatic intolerance after spaceflight. Journal of Applied
Physiology 81, 7–18.

Charles, J. B., et al. (1994). Cardiopulmonary function. In Space Physiology and Medicine, ed.N ICOGOSSIAN, A. E., LEACHHUNTOON, C. & POOL, S. L., 3rd edn, pp.286–304. Lea & Febiger, Philadelphia. Medicine 63, 439.

Convertino, V. A., et al. (1990). Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension. Journal of Applied Physiology 68, 1458–1464.

Fritsh, J. M. & Eckberg, D. L. (1992). Effects of weightlessness on human baroreflex function. Aviation, Space, and Environmental Medicine 63, 439.

Rea, R. F. & Eckberg, D. L. (1987). Carotid baroreceptor-muscle sympathetic relation in humans. American Journal of Physiology 253, R929–934.