Nocturnal lower body positive pressure to counteract microgravity-induced cardiac remodeling/atrophy

The following is the abstract of the article discussed in the subsequent letter:

	ABSTRACT

Perhonen, Merja A., Fatima Franco, Lynda D. Lane, Jay C. Buckey, C. Gunnar Blomqvist, Joseph E. Zerwekh, Ronald M. Peshock, Paul T. Weatherall, and Benjamin D. Levine. Cardiac atrophy after bed rest and spaceflight. J Appl Physiol 91: 645-653, 2001.Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 ± 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 ± 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 ± 12.2 vs. 153.4 ± 12.1 g, P = 0.81). Mean wall thickness decreased (4 ± 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 ± 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 ± 2.7% (P = 0.06) and RV end-diastolic volume by 16 ± 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 ± 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.

	LETTER

To the Editor: Perhonen and co-workers (4) report that existence in simulated and actual microgravity leads to cardiac atrophy. I thank the authors for their interesting, convincing, and important work. In their DISCUSSION, they speculate that chronic lack of cardiac distension in microgravity contributes to cardiac atrophy, as previously hypothesized (7). This idea raises the possibility of using nocturnal lower body positive pressure (LBPP) as a countermeasure against microgravity-induced cardiac atrophy.

Application of LBPP during sleep in microgravity could potentially reproduce the central fluid volume redistribution and cardiac distension experienced while recumbent for several hours per night on Earth. LBPP is a relatively benign and technically simple procedure, physiologically similar to head-out water immersion in 1 G (1). If lack of cardiac distension for several hours per night causes cardiac remodeling and reduced myocardial mass in chronic microgravity, then replacement via LBPP of this nightly cardiac distension may help prevent such myocardial atrophy.

Previous work demonstrates that central volume expansion at night does not elicit diuresis to the extent that similar volume expansion provokes during the day (e.g., Ref. 5). Therefore, nocturnal LBPP should not exacerbate microgravity-induced hypovolemia if nighttime antidiuresis operates during spaceflight similarly to Earth-bound circadian conditions.

In regard to microgravity-induced hypovolemia, from the discussion of Perhonen et al. (4) on diuresis during the first 24 h of bed rest, a reader could reasonably conclude that a similar renal response occurs during spaceflight. However, diuresis is not seen in flight; in fact, existing data suggest acute and chronic antidiuresis early in spaceflight (2, 3, 6). I respect that Perhonen et al. did not state that "spaceflight causes diuresis." However, because this is a widespread misconception, these differences between bed rest and spaceflight need to be explicitly recognized.

	REFERENCES

1.   Geelen, G, Kravik SE, Hadj-Aissa A, Leftheriotis G, Vincent M, Bizollon CA, Sem-Jacobsen CW, Greenleaf JE, and Gharib C. Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men. J Appl Physiol 66: 792-799, 1989[Abstract/Free Full Text].

2.   Leach, CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, and Krauhs JM. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 81: 105-116, 1996[Abstract/Free Full Text].

3.   Norsk, P, Drummer C, Rocker L, Strollo F, Christensen NJ, Warberg J, Bie P, Stadeager C, Johansen LB, Heer M, Gunga HC, and Gerzer R. Renal and endocrine responses in humans to isotonic saline infusion during microgravity. J Appl Physiol 78: 2253-2259, 1995[Abstract/Free Full Text].

4.   Perhonen, MA, Franco F, Lane LD, Buckey JC, Blomqvist CG, Zerwekh JE, Peshock RM, Weatherall PT, and Levine BD. Cardiac atrophy after bed rest and spaceflight. J Appl Physiol 91: 645-653, 2001[Abstract/Free Full Text].

5.   Shiraki, K, Konda N, Sagawa S, Claybaugh JR, and Hong SK. Cardiorenal-endocrine responses to head-out immersion at night. J Appl Physiol 60: 176-183, 1986[Abstract/Free Full Text].

6.   Watenpaugh, DE. Fluid volume control during short-term space flight and implications for human performance. J Exp Biol 204: 3209-3215, 2001[Abstract/Free Full Text].

7.   Watenpaugh, DE, and Hargens AR. The cardiovascular system in microgravity. In: Handbook of Physiology. Environmental Physiology. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 4, vol. I, chapt. 29, p. 631-674.

Donald E. Watenpaugh, Naval Submarine Medical Research Laboratory Box 900 Groton, Connecticut 06349-5900 E-mail: watenpaugh{at}nsmrl.navy.mil

	REPLY

To the Editor: Dr. Watenpaugh presents an interesting hypothesis, namely, that providing a positive pressure to the lower part of the body at night, also called LBPP, could stretch the heart and minimize cardiac atrophy during exposure to microgravity. Pilot work in our laboratory could not confirm a sustained increase in either central venous pressure or stroke volume from LBPP, possibly due to stress-relaxation of the venous capacitance vessels or even translocation of blood past the heart into the head and neck. Therefore, we have not been enthusiastic about applying this stimulus as a tool to expand the heart during our experiments. However, the idea certainly is intriguing, and we look forward to seeing such experiments conducted by Dr. Watenpaugh or others.

Dr. Watenpaugh also rightly points out that a diuresis has not been observed during early spaceflight, and we were careful not to state so explicitly. However, as noted by Dr. Watenpaugh himself (2), much of this failure may be due to the specific circumstances of flight experiments and the specific body position to which the comparison is being made. In space, the first measurements are usually not made until after the astronauts have been lying for many hours with their feet up in the air in the "prelaunch" position. Thus much of the short-term diuresis and natriuresis that would normally occur with the transition from standing upright in 1 G to microgravity has already occurred before launch. Subsequent measurements are then affected by limited fluid intake during the first few hours in space, in part because of the development of space motion sickness and also because of reduced access to fluids. Ultimately, it has been well documented that plasma volume is reduced early during exposure to space flight (1), although it is not certain whether this reduction occurs in the kidney or in the extravascular space. We agree with Dr. Watenpaugh's speculation (2) that if an astronaut could be transported immediately from the upright position on Earth to space then a diuresis would likely be observed, as has been noted in virtually all ground-based models.

	FOOTNOTES

10.1152/japplphysiol.01016.2001

	REFERENCES

1.   Leach, CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, and Krauhs JM. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 81: 105-116, 1996.

2.   Watenpaugh, DE. Fluid volume control during short-term space flight and implications for human performance. J Exp Biol 204: 3209-3215, 2001.

Benjamin Levine, Institute for Exercise and Environmental Medicine Presbyterian Hospital of Dallas Dallas, Texas 75231-5129 E-mail: benjaminlevine{at}texashealth.org