Effects of Prolonged Head-Down Bed Rest on Cardiac and Vascular Baroreceptor Modulation and Orthostatic Tolerance in Healthy Individuals.

Franca Barbic,Dana Shiffer,Jens Tank,André Diedrich,Alberto Porta,Maura Minonzio,Peter Gauger,Beatrice Cairo,Karsten Heusser,Roberto Antonio Zamuner,Raffaello Furlan,Jens Jordan

doi:10.3389/fphys.2019.01061

Abstract

Orthostatic intolerance commonly occurs after prolonged bed rest, thus increasing the risk of syncope and falls. Baroreflex-mediated adjustments of heart rate and sympathetic vasomotor activity (muscle sympathetic nerve activity – MSNA) are crucial for orthostatic tolerance. We hypothesized that prolonged bed rest deconditioning alters overall baroreceptor functioning, thereby reducing orthostatic tolerance in healthy volunteers. As part of the European Space Agency Medium-term Bed Rest protocol, 10 volunteers were studied before and after 21 days of −6° head down bed rest (HDBR). In both conditions, subjects underwent ECG, beat-by-beat blood pressure, respiratory activity, and MSNA recordings while supine (REST) and during a 15-min 80° head-up tilt (TILT) followed by a 3-min −10 mmHg stepwise increase of lower body negative pressure to pre-syncope. Cardiac baroreflex sensitivity (cBRS) was obtained in the time (sequence method) and frequency domain (spectrum and cross-spectrum analyses of RR interval and systolic arterial pressure – SAP, variability). Baroreceptor modulation of sympathetic discharge activity to the vessels (sBRS) was estimated by the slope of the regression line between the percentage of MSNA burst occurrence and diastolic arterial pressure. Orthostatic tolerance significantly decreased after HDBR (12 ± 0.6 min) compared to before (21 ± 0.6 min). While supine, heart rate, SAP, and cBRS were unchanged before and after HDBR, sBRS gain was slightly depressed after than before HDBR (sBRS: −6.0 ± 1.1 versus −2.9 ± 1.5 burst% × mmHg−1, respectively). During TILT, HR was higher after than before HDBR (116 ± 4 b/min versus 100 ± 4 b/min, respectively), SAP was unmodified in both conditions, and cBRS indexes were lower after HDBR (α index: 3.4 ± 0.7 ms/mmHg; BRSSEQ 4.0 ± 1.0) than before (α index: 6.4 ± 1.0 ms/mmHg; BRSSEQ 6.8 ± 1.2). sBRS gain was significantly more depressed after HDBR than before (sBRS: −2.3 ± 0.7 versus −4.4 ± 0.4 burst% × mmHg−1, respectively). Our findings suggest that baroreflex-mediated adjustments in heart rate and MSNA are impaired after prolonged bed rest. The mechanism likely contributes to the decrease in orthostatic tolerance.

Highlights

In 1944, Dock pointed out that “The physician must always consider complete bed rest as a highly un-physiologic and definitely hazardous form of therapy, to be ordered only for specific indications and discontinued as early as possible” (Dock, 1944)
The assessment of sBRS considers how the Diastolic arterial pressure (DAP) value relates to the occurrence of a muscle sympathetic nerve activity (MSNA) burst accounting for the baroreflex latency (Hart et al, 2010)
As previously described (Hart et al, 2010; Barbic et al, 2015; Marchi et al, 2015), DAP values were grouped into bins of 1 mmHg; the percentage of times that a MSNA burst was detected as associated with the considered

Summary

Introduction

In 1944, Dock pointed out that “The physician must always consider complete bed rest as a highly un-physiologic and definitely hazardous form of therapy, to be ordered only for specific indications and discontinued as early as possible” (Dock, 1944). The statement, which challenged medical beliefs of that period, is supported by numerous physiological investigations and clinical observations. Bed rest is associated with reductions in both effective circulating blood volume and cardiac output. Prolonged bed rest predisposes to the common hospitalization-associated disability syndrome (Allen et al, 1999; Covinsky et al, 2011; Ettinger, 2011). Orthostatic intolerance and syncope have been observed after prolonged bed rest in various clinical settings (Feldstein and Weder, 2012; Guerin et al, 2016; Tzur et al, 2018). Weightlessness elicited changes in muscle sympathetic nerve activity (MSNA) (Ertl et al, 2002) and in baroreflex heart rate regulation (Cox et al, 2002; Eckberg et al, 2010)

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Conclusion