Trial Report Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt −5° in middle-aged healthy men, 1985, Gaffney et al.

[SNT Gatchaman]

Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt −5° in middle-aged healthy men
Gaffney; Nixon; Karlsson; Campbell; Dowdey; Blomqvist

Cardiovascular deconditioning after prolonged bedrest has been attributed to inactivity. To examine the role of the altered distribution of body fluids, healthy men, aged 41 to 48 years, were studied before, during and after a 20-hour period of bedrest with head-down tilt (-5’).

This intervention produces a marked central shift of intravascular and interstitial fluid, but the short duration minimizes the effects of inactivity. Central venous pressure, cardiac output and stroke volume all increased significantly (p <0.05) from supine baseline mean values; central venous pressure from 8.6 to 12.6 cm H20, cardiac output from 6.9 to 7.9 liters/min, and stroke volume from 104 to 113 ml after 15 minutes of tilt, but all values returned to baseline within 20 hours. Supine central venous pressure afler tilt was 7.4 cm H20, cardiac output 5.7 liters/min and stroke volume 84 ml. Blood volume decreased 0.51 liters. After tilt, orthostatic stress produced a higher heart rate (90 ± 18 vs 88 ± 12 beats/min). Maximal oxygen consumption decreased (2.36 ± 0.41 vs 2.62 ± 0.48 liters/min), mainly owing to reduced stroke volume (87 ± 22 vs 107 ± 18 ml, p <0.05).

Thus, tilt produced a transient increase in central venous pressure, stroke volume and cardiac output, but supine mean values were below baseline levels after 20 hours. The post-tilt state was qualitatively and quantitatively similar to that seen after 2 to 3 weeks of bedrest or several days of spaceflight. These results are also similar to those from a previously studied group of ten 20- to 30-year-old normal men. However, the increase in central venous pressure tended to be larger and of longer duration in the middle-aged group. Furthermore, in the young men the initial increase in stroke volume produced relative bradycardia, with no change in cardiac output and arterial pressure. Cardiac output increased in the middle-aged group, but arterial pressure was controlled by vasodilatation. Heart rate did not change.

The results support the concept that cardiovascular deconditioning after bedrest is primarily an adaptation to a postural fluid shift rather than to inactivity. Age-related differences in hemodynamic responses to central fluid shifts appear to be present.

Link | PDF (The American Journal of Cardiology)

 

[SNT Gatchaman]

This 1985 paper appears to be referenced in recent long covid papers to support the idea that people can become deconditioned and develop POTS / OI in as little as 20 hours of acute illness. Eg Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID (2023)

As noted in the final paragraph of the abstract —

The results support the concept that cardiovascular deconditioning after bedrest is primarily an adaptation to a postural fluid shift rather than to inactivity. Age-related differences in hemodynamic responses to central fluid shifts appear to be present.

Also this is with 5° head-down tilt, which is unquestionably not something that happens to real people in real life.

Also also, this is middle-aged men, so not the predominant demographic seen in LC/ME.

 

[Hutan]

There's a paywall, so I can't check. I find the results given in the abstract a bit unclear. What parameters remained altered after the 20 hours of bedrest, and how long did they stay altered?

 

[SNT Gatchaman]

They don't specify. This study followed similar studies in younger men (20s) in 1979 and 1980. These followed zero-g studies in SkyLab and were designed to simulated zero-g. Bed rest, supine at 0° did not cause the same effect. But head-down tilt did. Also water immersion but that had hydrodynamic gradient confounders. I can't see these earlier studies described duration of abnormality, but they showed OI physiology using lower body negative pressure (similar to the study that showed POTS wasn't anxiety paper from the late 2000s).

The head down tilt method came from earlier Russian cosmonaut studies. Presumably there was a reasonably rapid return to normality (eg over subsequent 20 hours of fluid de-shifting) but I'm not sure this will be detailed - I'll look.

In the meantime here's a liberal quote from this paper's discussion —

Several lines of evidence argue against inactivity being the major cause of deconditioning after bedrest. First, this and previous studies of short periods of bedrest with head-down tilt+ documented deconditioning in the absence of any prolonged inactivity, Myocardial and musculoskeletal adaptations to inactivity would be measured in days to weeks rather than the 20 hours of inactivity used in our studies. Second, exercise in the supine position during bedrest, with programs ranging from heavy dynamic exercise to static efforts, generally fails to prevent the development of cardiovascular dysfunction. Several studies of supine exercise during bedrest, recently reviewed by Blomqvist and Stone,* showed little or no protection. Third, if inactivity is a major factor, physical training should accelerate recovery, but this was not found in a recent study by DeBusk et ali. These investigators postulated that the mere exposure to orthostatic stress was sufficient to overcome the deconditioning associated with bedrest. These data, combined with the fact that prolonged bedrest, head-down tilt, upright water immersion and spaceflight produce similar states of cardiovascular dysfunction, suggest that the primary cause is a response to an altered distribution of body fluids and intravascular pressures. The common denominator of these interventions is a cephalad fluid shift and a transient increase in cardiac filling pressure.

 

[Arnie Pye]

I would have thought a head down tilt while sleeping or spending time in bed would give people headaches (possibly severe) as well as the indigestion from hell if the subjects had slightly less than perfect junctions between stomach and esophagus (which I would think was common in people in their 40s). I would never have volunteered for any research like this.

 

[rvallee]

In response to the crap paper about 20h of inactivity being their preferred cause of Long Covid, plenty of long haulers have shared their past experiences of having been bedbound for other reasons, like ICU stay or recovering from surgery, and how easy and quick it was to get back to normal, because there was no PEM.

It's so frustrating how it's a common trope for MDs to acknowledge that patients know their body best and they should trust us, but literally invent entire illness models, all psychosomatic of course, for the cases when they just, for some reason, disagree. Obviously a few days of inactivity doesn't cause deconditioning, no smart person actually believes that. Most people will have been severely ill 2-3 times in their lives, stuck in bed for a few days with flu, food poisoning or something like it. It doesn't cause that at all.

Just like the equally ridiculous, and very old, causality-defying assertion of "talking too much about Long Covid caused Long Covid", it's maddening how ridiculous the claims are, how obviously wrong they are, how they might as well be about alien bugs invading our bodies, and yet nearly the entire medical profession plays along with it.

 

[Mij]

I rested for 6 yrs PVFS and was never deconditioned. I started running again right where I left off when I started feeling better again, but PEM set in and I had to stop.

 

[Hutan]

This intervention produces a marked central shift of intravascular and interstitial fluid, but the short duration minimizes the effects of inactivity. Central venous pressure, cardiac output and stroke volume all increased significantly (p <0.05) from supine baseline mean values; central venous pressure from 8.6 to 12.6 cm H20, cardiac output from 6.9 to 7.9 liters/min, and stroke volume from 104 to 113 ml after 15 minutes of tilt, but all values returned to baseline within 20 hours. Supine central venous pressure afler tilt was 7.4 cm H20, cardiac output 5.7 liters/min and stroke volume 84 ml. Blood volume decreased 0.51 liters. After tilt, orthostatic stress produced a higher heart rate (90 f 18 vs 88 f 12 beats/min). Maximal oxygen consumption decreased (2.36 f 0.41 vs 2.62 f 0.48 liters/min), mainly owing to reduced stroke volume (87 f 22 vs 107 f 18 ml, p <0.05).

Thus, tilt produced a transient increase in central venous pressure, stroke volume and cardiac output, but supine mean values were below baseline levels after 20 hours. The post-tilt state was qualitatively and quantitatively similar to that seen after 2 to 3 weeks of bedrest or several days of spaceflight. These results are also similar to those from a previously studied group of ten 20- to 30-year-old normal men. However, the increase in central venous pressure tended to be larger and of longer duration in the middle-aged group. Furthermore, in the young men the initial increase in stroke volume produced relative bradycardia, with no change in cardiac output and arterial pressure. Cardiac output increased in the middle-aged group, but arterial pressure was controlled by vasodilatation. Heart rate did not change.

With the benefit of a night's sleep, they seem to be saying this, for example for central venous pressure
Supine central venous pressure - 8.6 cm H2O when first supine,
increasing to a maximum of 12.6 cm H2O during the headdown tilt,
but then returning to baseline over the 20 hours spent in the headdown tilt.

However, after the tilt (how much time after the tilt? and what did the person do after the tilt - lie supine without head down, or sit, or stand up, or just go about their normal business?), supine central venous pressure was 7.4 cm H2O. So, they stopped the 20 hours of lying head down, did something that wasn't that for an unspecified period of time, and then, when they became supine again (but not head down), the supine central venous pressure was a bit reduced compared to the baseline.

Crucially, the abstract does't tell us how long the lower supine central venous pressure (and other altered parameters) were maintained after the end of the head down tilt. What we appear to be seeing is an adaptation to lying head down, which is perfectly achieved over 20 hours.

but all values returned to baseline within 20 hours.

Possibly, adaptation to another relationship to gravity can be achieved in a similar time, in healthy people?

The results support the concept that cardiovascular deconditioning after bedrest is primarily an adaptation to a postural fluid shift rather than to inactivity. Age-related differences in hemodynamic responses to central fluid shifts appear to be present.

The conclusion of the abstract seems to hint at transient effects - once the postural fluid shift changes, the body re-adapts.

 

[SNT Gatchaman]

See also summary thread The Dallas Bed Rest and Training Study (2019) which covers 40 years of evaluations in the same subjects.

 

[Hubris]

I rested for 6 yrs PVFS and was never deconditioned. I started running again right where I left off when I started feeling better again, but PEM set in and I had to stop.

I have had surgery complications recently that forced me to stay in bed completely horizontal 24/7 for months, after about a month I was starting to feel the deconditioning as extra fatigue and weakness - but it is maybe, 0.1% compared to my ME symptoms? And you can, you know, just walk a bit in the house and it goes away. Maybe the most trivial "health problem" I've ever had.

 

[SNT Gatchaman]

What parameters remained altered after the 20 hours of bedrest, and how long did they stay altered?

Crucially, the abstract does't tell us how long the lower supine central venous pressure (and other altered parameters) were maintained after the end of the head down tilt. What we appear to be seeing is an adaptation to lying head down, which is perfectly achieved over 20 hours.

The conclusion of the abstract seems to hint at transient effects - once the postural fluid shift changes, the body re-adapts.

I've had a read through this group's original studies —

Early cardiovascular adaptation to simulated zero gravity (1979, Journal of Applied Physiology)
Early cardiovascular adaptation to zero gravity simulated by head-down tilt (1980, Acta Astronautica)

It's not clearly spelled out but the implication is that there is swift reversal of the adaptations, back to normal. The 5-6° head-down protocol was derived from Russian studies, that trialled 0° to 12°. This group settled on 5° and state it was well tolerated by the volunteers. I can't access the 1976 Russian paper.

The 1979 paper says —

Plasma renin activity, aldosterone, and antidiuretic hormone were depressed initially but returned to base line within 24 h.

ETA: No it's there in the 1980 paper (actually in the abstract) —

The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5°, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 hr. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin and aldosterone inhibition.

 

[SNT Gatchaman]

Actually that's still ambiguous and I don't think this means 6 hours after the tilt, but 6 hours into the tilt - but confined to haemodynamic measures (which have been compensated for). See the middle graph below.

 

[Sean]

Several lines of evidence argue against inactivity being the major cause of deconditioning after bedrest....

Third, if inactivity is a major factor, physical training should accelerate recovery, but this was not found in a recent study by DeBusk et ali.

See also null results from PACE, et al.

 

[SNT Gatchaman]

I would have thought a head down tilt while sleeping or spending time in bed would give people headaches (possibly severe) as well as the indigestion from hell if the subjects had slightly less than perfect junctions between stomach and esophagus (which I would think was common in people in their 40s). I would never have volunteered for any research like this.

See this new study report where volunteers were 6° head-down permanently for 60 days !! "all activities and hygiene maintenance took place in this position".

Artificial gravity during a spaceflight analog alters brain sensory connectivity (2023)

 

[sneyz]

I rested for 6 yrs PVFS and was never deconditioned. I started running again right where I left off when I started feeling better again, but PEM set in and I had to stop.

This has been my experience too! Years of inactivity, then straight back to being in better shape than most of my friends and family who exercise regularly… I’ve abandoned exercise almost entirely due to PEM, but still preform way beyond what would be expected on the 3-4 bike rides I do in a year.

 

[SNT Gatchaman]

On the subject of recovery from bedrest and spaceflight / analogue studies, note these comments on social media in response to simplistic "criticisms" from a member of the BPS/FND school —

Re: Muscle abnormalities worsen after post-exertional malaise in long COVID (2024, Nature Communications)

Interesting and longitudinal design helpful - but small so needs replication but also needs a bed rest or similar comparison - are we seeing the cause or the effect?

Dear Alan, please bear with me for 2 weeks, when we publish our results of a bed rest study in Cell Reports Medicine. I am also excited to see this work replicated elsewhere, but this work is in line with previous studies on similar topics (even one dating back from 1980s)

Also, it’s important to remember that people undergoing bed rest get better when they start exercising again, but this is not the case in long COVID patients. They get worse…

No, we don’t need to see this because we already have abundant data from people who are de-loaded from such circumstances as bedrest and space flight. These data are what we often use to teach undergraduates in their very first exercise physiology course. Nothing new there.

(It's a poorly thought out criticism anyway as the LC subjects were not bed-bound, but at the mild end of the disease spectrum, with actimetry-proven daily step counts of 4000 - although as we know even "mild" disease is significantly disabling).

Carson | Wüst | Davenport