Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

Abstract

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals.

exposure to microgravity, as well as its ground-based analog, 6° head-down bed rest (HDBR), results in numerous cardiovascular adaptations, including reduced cardiac function (22), reduced aerobic power (7, 21, 37), as well as diminished ability to withstand the upright posture (i.e., reduced orthostatic tolerance) (2–4, 18, 26, 27, 40). Identification of effective countermeasures against this reduction in orthostatic tolerance has been actively pursued. The effectiveness of countermeasures, such as exercise training and repeated simulated gravity exposure, has been examined (2, 18, 26, 27); however, an easily implemented and effective countermeasure has yet to be identified.

Previous attempts to identify effective countermeasures against simulated and actual microgravity-induced orthostatic intolerance have resulted in limited success. Studies utilizing acute maximal exercise prior to cessation of microgravity exposure (27), exercise training throughout microgravity exposure (17), as well as exercise training with concomitant lower-body negative pressure (LBNP) (25, 40) have resulted in either no change or only modest improvements in orthostatic tolerance following actual (or simulated) microgravity exposure. Studies investigating acute administration of sympathomimetic drugs have helped prevent (30) or did not alter (34) orthostatic tolerance following microgravity exposure. It is important to note that many of the investigated countermeasures require significant time (e.g., daily exercise throughout exposure to microgravity) and resources (e.g., financial, equipment space, etc.) to carry out. Therefore, the development of a safe and effective countermeasure that can be applied with relatively little additional time or resources would be of particular importance.

Skin surface cooling increases plasma norepinephrine concentration (14) and skin sympathetic nerve activity (32), decreases skin blood flow (10), as well as increases mean arterial blood pressure (MAP) (10, 14) in resting humans. With the use of tube-lined perfusion suits as the cooling stimulus, Durand et al. (14) found that skin surface cooling improved orthostatic tolerance (via graded LBNP) by >35%. However, the effectiveness of skin surface cooling as a countermeasure to the reduction in orthostatic tolerance observed following exposure to microgravity, or its ground-based analog HDBR, remains unknown.

The aim of the current study was to test the hypothesis that skin surface cooling would be an effective countermeasure against the reduced orthostatic tolerance resulting from prolonged HDBR. Positive findings from this investigation may have an important implication for the treatment of individuals upon return to a gravity environment post-spaceflight, as well as immobilized or bed-stricken individuals.

METHODS

Subjects

Eight subjects (six men and two women) voluntarily participated in the investigation (age, 44 ± 9 yr; height, 178 ± 13 cm; mass, 86 ± 14 kg; mean ± SD). All procedures conformed to the standards set by the Declaration of Helsinki. Each subject signed an informed consent that was approved by the Institutional Review Boards at the University of Texas Southwestern Medical Center (Dallas, TX), the General Clinical Research Center at the University of Texas Southwestern Medical Center, and Texas Health Presbyterian Hospital (Dallas, TX). Prior to participation, all subjects were familiarized with the testing protocols. Subjects were healthy, nonsmokers, free of known cardiovascular, respiratory, and metabolic diseases, and not using prescription or over-the-counter medications. Subjects were not permitted to consume alcohol 24 h before any of the scheduled experiments or throughout bed rest. Subjects were also asked to refrain from the consumption of caffeinated beverages 12 h before the scheduled experiments.

Study Timeline

The entire study consisted of 5 experimental days (2 pre-HDBR days and 3 post-HDBR days) and 18 days of 6° HDBR. The 2 pre-HDBR days were always performed in similar order. Pre-HDBR day 1 consisted of orthostatic-tolerance testing during normothermic conditions and determination of blood volume (carbon monoxide rebreathing). Pre-HDBR day 2 consisted of the determination of multiple cardiovascular and neural responses to submaximal steady-state orthostatic challenges during normothermic and skin surface cooling conditions. Two days after this pre-HDBR testing, subjects began 6° HDBR. The 3 post-HDBR tests days were performed on days 16, 17, and 18 of HDBR. Post-HDBR day 16 or day 18 consisted of orthostatic-tolerance testing during either normothermic or skin surface cooling conditions (order of thermal condition randomized). Similar to pre-HDBR day 1, the determination of blood volume was performed on the same day as the normothermic orthostatic tolerance testing (i.e., either day 16 or day 18). On day 17, experimental testing was identical to pre-HDBR day 2.

Instrumentation

Pre-HDBR day 1 and post-HDBR days 16 and 18.

Upon entering the laboratory, subjects were dressed in a tube-lined perfusion suit, enabling the control of skin (T_sk) and core temperatures (T_core) via changing the temperature of the water perfusing the suit. The suit covered the entire body with exception of the hands, feet, neck, face, and head. For post-HDBR trials, subjects were transported to the laboratory in the supine position and remained in this position throughout the experimental days. T_core was measured using a telemetry temperature pill, which has been validated to adequately reflect other indices of internal temperature (28). The temperature pill was swallowed by subjects at least 1 h before data collection. Whole-body T_sk was measured from the electrical average of six thermocouples (36) fixed to the skin of the chest, upper back, lower back, abdomen, thigh, and calf with porous adhesive tape. Arterial blood pressure was measured using auscultation of the brachial artery (SunTech Medical Instruments, Morrisville, NC), as well as continuous finger-cuff photoplethysmography (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands). Only the auscultation arterial blood pressure data are presented, as finger-derived blood pressures were used solely to identify pre-syncope during tolerance testing. Heart rate was collected from an ECG signal (Agilent, Santa Clara, CA) interfaced with a cardiotachometer (1,000 Hz sampling rate; CWE, Ardmore, PA).

A laser doppler flowmeter probe (Perimed, North Royalton, OH) was placed on dorsal forearm skin mid-way between the wrist and the elbow. Laser doppler indices of skin blood flow [arbitrary units (A.U.)] were used to calculate cutaneous vascular conductance (CVC) using the following formula: CVC = skin blood flux (A.U.)/MAP × 100.

Pre-HDBR day 2 and post-HDBR day 17.

Upon entering the laboratory, subjects were instrumented as described above with the following additional instrumentation on these experimental days. A catheter was inserted into the basilic vein of a subject's arm, with the tip of the catheter advanced into the superior vena cava to measure central venous pressure (CVP). Catheter position was confirmed by 1) the distance inserted into the body, 2) appropriate pressure waveforms, and 3) rapid rise and fall in CVP during Valsalva and Müller maneuvers, respectively. The catheter was connected to a calibrated pressure transducer with the zero reference set at the subjects' midaxillary line. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography (from the contralateral arm relative to the arm with the central catheter). Cardiac output was determined using carbon dioxide (13)- or acetylene (11, 38)-rebreathing techniques as previously described. Following completion of the pre- and post-HDBR testing of the first two subjects using the carbon dioxide-rebreathing technique, the acetylene technique was used for the remaining subjects given the availability of the acetylene technique in the lab following these initial two subjects.

Multifiber recordings of muscle sympathetic nerve activity (MSNA) were obtained using a tungsten microelectrode positioned in the common peroneal nerve. A reference electrode was placed subcutaneously ∼2–3 cm from the recording electrode. The position of the recording electrode was adjusted until a site was attained in which bursts of MSNA were identified using previously established criteria (39). The nerve signal was amplified, passed through a bandpass filter with a bandwidth of 700–2,000 Hz, and integrated with a time constant of 0.1 s (University of Iowa Bioengineering, Iowa City, IA).

Experimental Protocols

Orthostatic tolerance testing: pre-HDBR day 1, post-HDBR days 16 and 18.

Orthostatic tolerance was determined pre-HDBR day 1, post-HDBR day 16, and post-HDBR day 18 using graded LBNP at 3-min stages starting at 20 mmHg and decreasing by 10 mmHg/stage until test termination. Testing was terminated on predetermined signs of ensuing syncope, including subject “feeling faint”, subject reporting he/she can no longer tolerate the test, pallor, diaphoresis, a sustained drop in MAP of >25 mmHg or a continued systolic blood pressure <80 mmHg, relative bradycardia, and pronounced narrowing pulse pressure accompanying the reduction in arterial blood pressure. Pre-HDBR orthostatic tolerance was determined only while subjects were normothermic (i.e., 34°C water perfused through suit). Post-HDBR orthostatic tolerance was determined during both normothermic (34°C water through the tube-lined suit) and skin surface cooling conditions (i.e., ∼12–15°C water through the tube-lined suit for ∼30 min prior to tolerance testing, as well as throughout tolerance testing) in random order on either day 16 or day 18. The effectiveness of skin surface cooling on orthostatic tolerance prior to bed rest (i.e., pre-HDBR) was not examined, as that question has previously been investigated (14). Moreover, the focus of the present investigation was to specifically address the effectiveness as a countermeasure following HDBR exposure, as well as potential related mechanisms independent of an effect pre-HDBR or potential interactive effects following HDBR.

Submaximal steady-state LBNP testing: pre-HDBR day 2 and post-HDBR day 17.

Throughout instrumentation, 34°C water was perfused through the tube-lined suit. After instrumentation was completed (∼90 min), data were collected for a 30-min baseline period. During basal data collection, two to three rebreathe cardiac output trials were performed, as well as forearm blood-flow measures. After baseline data collection, LBNP at 15 mmHg was applied for 10 min, immediately followed by 30 mmHg for 10 min (20 min total time). Forearm blood flow was measured during min 2–4 of both LBNP stages. Arterial blood pressure was measured via brachial cuff immediately preceding and following the forearm blood-flow measures and was used for the calculation of forearm vascular resistance for each stage of data collection. Rebreathe cardiac output trials were performed between min 5 and 10 for each LBNP. Subjects were asked to remain relaxed and motionless throughout data collection. Subsequently, skin surface cooling was initiated by perfusing ∼12–15°C water through the tube-lined suit for ∼30 min. This cooling paradigm previously increased MAP by ∼5–10 mmHg (10, 14). After ∼30 min of cooling, the above protocol was repeated (i.e., baseline data collection followed by 15 and 30 mmHg LBNP). Cooling was slightly adjusted between subjects to administer maximal skin surface cooling while minimizing/eliminating skeletal muscle shivering. However, the cooling protocol used for each individual on his/her pre-HDBR day 2 was identical (i.e., the temperature and duration) to his/her post-HDBR steady-state LBNP day and the post-HDBR tolerance test.

Statistical Analysis

Statistical significance for all tests was set at P < 0.05. Comparisons of resting physiological variables between pre-HDBR and post-HDBR were made using paired t-tests. Comparisons of steady-state physiological variables during LBNP trials between thermal conditions (i.e., normothermia vs. skin surface cooling conditions on post-HDBR day 17) were made using two-way repeated measures ANOVA. If a significant interaction were identified, multiple comparison tests were used to determine specific differences. When normality was not achieved, as was the case for forearm vascular-resistance responses, the data underwent a log transformation prior to the statistical analysis. Orthostatic tolerance, expressed as cumulative stress index (CSI), was compared between pre-HDBR and post-HDBR (during normothermia and cooling) using one-way repeated measure ANOVA. The CSI was calculated for each LBNP protocol by summing the product of the applied negative pressure and the duration of the pressure stimulus for each stage of LBNP (mmHg LBNP·min). Values, with the exception of subject characteristics, are reported as mean ± SE.

RESULTS

Resting Cardiovascular Variables Pre- and Post-HDBR

Resting heart rate was increased post-HDBR (69 ± 3 bpm) compared with pre-HDBR (59 ± 2 bpm; P < 0.05), whereas MAP was unchanged (pre-HDBR: 90 ± 3; post-HDBR: 93 ± 4 mmHg). CVP decreased post-HDBR (3.8 ± 0.6 mmHg) compared with pre-HDBR (5.3 ± 0.9 mmHg; P < 0.05). Forearm blood flow and forearm vascular resistance were unchanged following HDBR.

As expected, blood volume (pre-HDBR: 6.3 ± 0.5 vs. post-HDBR: 5.5 ± 0.5 liters; P < 0.05) and plasma volume (pre-HDBR: 4.0 ± 0.3 vs. post-HDBR: 3.4 ± 0.3 liters; P < 0.05) were reduced following HDBR.

Response to Submaximal Steady-State 15 and 30 LBNP Pre- and Post-HDBR

Cardiovascular and neural responses to submaximal steady-state LBNP during normothermic and skin surface cooling conditions pre- and post-HDBR are summarized in Tables 1 and 2, respectively. During pre-HDBR testing, skin surface cooling decreased T_sk from 34.6 ± 0.1 to 29.1 ± 0.5 (P < 0.001), whereas T_core remained unchanged (normothermia: 37.1 ± 0.1 vs. skin surface cooling: 37.2 ± 0.1). Again, during post-HDBR testing, skin surface cooling decreased T_sk from 34.5 ± 0.2 to 28.7 ± 0.5 (P < 0.001). However, during post-HDBR testing, T_core slightly increased during cooling (normothermia: 37.0 ± 0.1 vs. skin surface cooling: 37.4 ± 0.1; P = 0.01). Skin surface cooling increased MAP during pre-HDBR (P = 0.027) and post-HDBR (P < 0.01) testing compared with the respective normothermic conditions. Despite these increases in MAP, there were no consistent increases in either cardiac output or total peripheral resistance in response to cooling during pre- and post-HDBR trials. Interestingly, while skin surface cooling increased CVP during pre-HDBR testing (P < 0.001), skin surface cooling did not significantly increase CVP after HDBR prior to or throughout the steady-state LBNP protocol (P = 0.164). The imposed level of cooling was not sufficient to significantly decrease CVC prior to LBNP, either pre-HDBR or post-HDBR. Subsequent LBNP also was not of a sufficient magnitude to decrease CVC pre-HDBR or post-HDBR. regardless of the thermal condition.

Table 1.

Cardiovascular and neural responses to submaximal steady-state LBNP between thermal conditions pre-HDBR

	Normothermia			Skin Surface Cooling
	Baseline	15 LBNP	30 LBNP	Baseline	15 LBNP	30 LBNP
HR, bpm	59 ± 2	64 ± 3	74 ± 4*,†	60 ± 1	60 ± 2	64 ± 2§
MAP, mmHg	90 ± 3	90 ± 3	86 ± 3*	96 ± 4§	95 ± 4§	92 ± 4*,†
CVP, mmHg	5.3 ± 0.9	2.1 ± 0.9*	0.5 ± 0.6*,†	7.3 ± 1.0§	3.3 ± 0.8*,†	1.6 ± 0.6*,†,§
FVR, mmHg · ml−1 · min−1/100 ml	49 ± 8	57 ± 7	56 ± 10	60 ± 9§	71 ± 6§	77 ± 5§
Cardiac output, liter	4.4 ± 0.6	4.0 ± 0.5	3.7 ± 0.6*	4.5 ± 0.5	4.2 ± 0.6	3.9 ± 0.5*
Stroke volume, ml	66 ± 9	58 ± 8	48 ± 9*	74 ± 9§	65 ± 9§	59 ± 8*,†
TPR, mmHg · l−1 · min−1	23 ± 3	25 ± 3	27 ± 4	24 ± 3	27 ± 4	27 ± 4
MSNA, burst/min	24 ± 5	28 ± 3	41 ± 5*	25 ± 6	34 ± 4	40 ± 4*
MSNA, burst/100 ml	39 ± 7	43 ± 3	56 ± 5*	44 ± 10	56 ± 6	61 ± 6*

LBNP, lower-body negative pressure; HDBR, head-down bed rest; HR, heart rate; MAP, mean arterial blood pressure; CVP, central venous pressure; FVR, forearm vascular resistance; TPR, total peripheral resistance; MSNA, muscle sympathetic nerve activity.

^*Significantly different from Baseline within the indicated thermal condition (P < 0.05);

^†significantly different from 15 mmHg LBNP within the indicated thermal condition (P < 0.05);

^§significantly different from Normothermia condition (P < 0.05).

Table 2.

Cardiovascular and neural responses to submaximal steady-state LBNP between thermal conditions post-HDBR

	Normothermia			Skin Surface Cooling
	Baseline	15 LBNP	30 LBNP	Baseline	15 LBNP	30 LBNP
HR, bpm	69 ± 3	78 ± 3*	92 ± 6*,†	69 ± 3	72 ± 4§	83 ± 6*,†,§
MAP, mmHg	93 ± 4	91 ± 4	86 ± 4*	97 ± 4§	93 ± 5§	92 ± 4*,†
CVP, mmHg	3.8 ± 0.6	1.9 ± 0.5*	1.0 ± 0.6*,†	4.1 ± 0.7	2.6 ± 0.7*	1.3 ± 0.7*,†
FVR, mmHg · ml−1 · min−1/100 ml	49 ± 3	60 ± 5	52 ± 4	66 ± 7§	77 ± 9§	88 ± 15§
Cardiac output, liter	4.6 ± 0.7	4.5 ± 0.5	3.9 ± 0.3*	4.8 ± 0.6	4.2 ± 0.5	4.0 ± 0.4*
Stroke volume, ml	62 ± 9	55 ± 7*	42 ± 4*,†	68 ± 9	55 ± 6*	48 ± 4*,†
TPR, mmHg · l−1 · min−1	22 ± 3	22 ± 2	24 ± 2	22 ± 3	24 ± 2	24 ± 2
MSNA, burst/min	33 ± 7	39 ± 6	47 ± 6*,†	35 ± 6	40 ± 6	48 ± 7*,†
MSNA, burst/100 ml	44 ± 8	48 ± 8	50 ± 6*	47 ± 8	52 ± 7	54 ± 5*

^*Significantly different from Baseline within the indicated thermal condition (P < 0.05);

^†significantly different from 15 mmHg LBNP within the indicated thermal condition (P < 0.05);

^§significantly different from Normothermia condition (P < 0.05).

The Effect of Skin Surface Cooling on Orthostatic Tolerance

The group-averaged orthostatic tolerance (indexed as CSI) for pre-HDBR was 1,037 ± 96 mmHg·min. Following HDBR exposure, orthostatic tolerance significantly decreased to 574 ± 63 mmHg·min, while subjects were normothermic (P < 0.001). Acute skin surface cooling increased orthostatic tolerance post-HDBR (797 ± 77 mmHg·min) compared with post-HDBR normothermic conditions (P = 0.029; see Fig. 1). However, skin cooling was not sufficient to return orthostatic tolerance to that observed prior to HDBR.

Fig. 1.

Group-averaged and individual orthostatic-tolerance data (expressed as cumulative stress index) during normothermia (NT) prior to head-down bed rest (HDBR; Pre NT) and post-HDBR during NT (Post NT) and skin surface cooling conditions (Post SSC). *Significantly different from pre-HDBR (P < 0.05); †significantly different from Post NT (P = 0.03); indiv, individual responses.

DISCUSSION

The primary finding of this investigation is that HDBR-induced orthostatic intolerance was partially reversed with acute application of skin surface cooling prior to and throughout orthostatic testing. Potential mechanisms responsible for the effectiveness of skin surface cooling as a countermeasure to orthostatic intolerance are likely related to a general increase in arterial pressure observed during the cooling stimulus.

It is widely accepted that exposure to either microgravity or HDBR decreases orthostatic tolerance (2–4, 18, 26, 27). As a result, development of effective countermeasures to protect against orthostatic intolerance upon return to Earth has been a particularly important area of interest, as it relates directly to astronaut safety and health. To date, however, countermeasures to protect against postflight (or HDBR) orthostatic intolerance involve exercise paradigms (16, 17, 27), volume expansion (5), pharmacological intervention (29, 30), or LBNP during exposure with (25, 33) or without (6, 20, 35) exercise. Other studies have investigated the effectiveness of acute pharmacological administration on microgavity-induced orthostatic intolerance (30, 34) with mixed success.

While a variety of countermeasures to microgravity-induced orthostatic intolerance has resulted in mixed findings, it is worth noting that many countermeasures require substantial time (e.g., daily exercise throughout exposure to microgravity) and resources (e.g., financial, equipment, space, etc.) to complete. Therefore, the development of an effective countermeasure that can be applied with relatively little additional time or resources would be of particular importance. Given that astronauts currently wear water-perfused suits during re-entry, the use of acute skin surface cooling could be incorporated without substantial added time or resources.

In 2004, Durand et al. (14) examined the effect of acute skin surface cooling applied prior to and throughout orthostatic-tolerance testing in ambulatory healthy individuals. In that study, orthostatic tolerance was augmented by skin surface cooling compared with normothermic testing conditions by ∼39% (range from ∼3% to 84% increase in tolerance, as indexed by the same CSI used in the present study). Consistent with those findings, the application of skin surface cooling in the current study improved orthostatic tolerance following HDBR by ∼45% (see Fig. 1). In fact, six of the eight subjects demonstrated 20% or more improvements in orthostatic tolerance (as indexed by CSI; ranging from ∼22% to 170% increased tolerance) during skin surface cooling trials, while one demonstrated an approximate 16% increase in tolerance. One subject showed a small reduction (∼7%) in tolerance with skin surface cooling compared with normothermic testing post-HDBR. It is interesting to note that this “nonresponsive” subject exhibited the greatest change in MSNA (burst incidence) following the HDBR (i.e., ∼29 burst/100 cardiac cycles). The average change in MSNA (burst incidence) for the remaining subjects post-HDBR was ∼0, with an approximately even distribution of subjects slightly increasing and decreasing MSNA following bed rest. Whether the large increase in MSNA post-HDBR in this subject had a role in the lack of response to skin surface cooling is not readily apparent.

The acute application of skin surface cooling increases plasma norepinephrine concentration (14), increases skin sympathetic nerve activity (32), and decreases skin blood flow (10). Skin surface cooling also increases MAP (10, 14, 15). In the aforementioned study by Durand et al. (14), they reported increased MAP in response to skin surface cooling at baseline and throughout graded LBNP compared with normothermic testing. Similar to those findings, in the current study, pre- and post-HDBR skin surface cooling increased MAP at rest and during −15 and −30 LBNP during the submaximal steady-state assessment (see Tables 1 and 2). Also, similar to the work of Durand et al. (14), heart rate was reduced during combined skin surface cooling and LBNP compared with normothermic trials both prior to and following HDBR.

Skin surface cooling during an orthostatic challenge of normothermic and heat-stressed individuals preserves cerebral blood velocity (and presumably, cerebral blood flow), as measured with transcranial Doppler techniques (41). Although not examined in the current study, it is hypothesized that similar responses were observed during cooling in the present subjects. Furthermore, while skin surface cooling of heat-stressed individuals (core temperature elevated ∼2°C) increased end-tidal CO₂ relative to heat stress alone (24)—a change that likely contributed to the preservation of cerebral perfusion—skin surface cooling of normothermic individuals does not change end-tidal CO₂ (14). Thus although not measured in the current study, it is expected that the applied cooling stimulus likewise did not change end-tidal CO_2.

Based on the current observations, a general increase in arterial blood pressure is likely the primary mechanism resulting in improvements in orthostatic tolerance. The lack of a statistically significant increase in total peripheral resistance or cardiac output, despite the consistent increase in MAP, is likely related to variability in individual responses to skin surface cooling (i.e., some individuals may exhibit greater vascular resistance responses, whereas others exhibit greater cardiac output responses). However, MSNA did not increase with skin cooling (see Tables 1 and 2), which is consistent with our prior findings (10). In contrast, Fagius and Kay (15) reported that arterial pressure and MSNA increased following exposure to environmental cold stress (i.e., a hypothermic surgical chamber). This may be due to differences in the magnitude of the cold stimulus between the studies. Regardless, the observed increase in arterial pressure could provide a greater “reserve” for reductions in arterial pressure during orthostatic challenge and therefore, greater tolerance.

CVP has been shown to increase during skin surface cooling (11, 14, 42). Likewise, in the current study, skin surface cooling resulted in elevated CVP at rest and during −15 and −30 LBNP prior to HDBR compared with LBNP while normothermic. Interestingly, for unknown reasons, skin surface cooling did not increase CVP following HDBR (see Table 2). It is possible that decreased blood volume after HDBR limited potential increases in CVP to this cooling stimulus. Furthermore, a change in the perception of cooling (i.e., central or peripheral) may have resulted in blunted responses leading to reduced changes in CVP following HDBR. Regardless, MAP was increased following HDBR with cooling.

The present data clearly demonstrate an increase in orthostatic tolerance upon application of skin surface cooling following ∼16–18 days of exposure to HDBR, indicating its effectiveness as a countermeasure to HDBR-induced (and presumably, microgravity-induced) orthostatic intolerance. Despite the benefit of this countermeasure, it may be that the study design limited the extent of the improvement. The skin surface cooling protocol was applied in a fashion through adjusting temperature (between 12°C and 15°C) and duration (∼30 ± 5 min) in each subject to minimize cooling-related shivering. We chose this approach, as shivering would interfere with the collection of some of the measured cardiovascular and neural variables, as well as have obvious detrimental operational consequences for astronauts. However, it is important to note that the individualized cooling protocol implemented during the pre-HDBR, steady-state LBNP trial (see methods) was repeated identically (i.e., temperature and duration) for each subject during their post-HDBR-submaximal, steady-state LBNP day and their post-HDBR-tolerance day trials. It is possible that a more profound skin surface cooling stimulus may have improved orthostatic tolerance to a greater extent than the protocol used in this study, particularly given the subjective observation that the perception of the cooling stimulus was attenuated post-HDBR. Such a possibility would not change the interpretation of the primary finding of this study (i.e., improved tolerance with skin surface cooling post-HDBR). However, a greater cooling stimulus may have more clearly delineated the mechanism(s) responsible for this occurrence.

A limitation of the current study is related to the interpretation of the steady-state LBNP testing for both pre-HDBR and post-HDBR, in which responses were only measured during 15 and 30 mmHg LBNP. While findings from these experimental days may provide insight into the role of cardiovascular or neural responses (particularly MSNA) as a mechanism for skin surface cooling improvements in orthostatic tolerance, the orthostatic challenge may be considered relatively mild. Considering that graded orthostatic tolerance testing often utilizes much greater LBNPs (e.g., 70–100 mmHg), findings during 15 and 30 mmHg LBNP may not fully apply during greater orthostatic challenges. Furthermore, more specific mechanisms explaining the improvement in orthostatic tolerance post-HDBR may have been manifested at higher stages of LBNP. That said, the current design was chosen to take into account a reduced orthostatic tolerance following exposure to HDBR. Therefore, while it was expected that all subjects could withstand steady-state LBNP up to 30 mmHg during the pre-HDBR testing, it was possible that some (or even many) subjects would not be able to withstand steady-state LBNP >30 mmHg following HDBR.

Perspective

Core body temperature increases during re-entry of the space shuttle (31). Given this observation, the currently used approach to cool astronauts within the pressurized space suit during re-entry is inadequate. Given the profound effects of heat stress in compromising blood pressure regulation (8, 9) and orthostatic tolerance (1, 12, 19, 23, 41), a more aggressive cooling stimulus may be warranted during re-entry. By incorporating a more aggressive cooling stimulus, the following two benefits will be realized: 1) hyperthermia associated with re-entry, as well as egress, would be greatly attenuated; and 2) improvements in orthostatic tolerance during this critical period of the mission.

In conclusion, acute application of skin surface cooling may serve as an effective and easily implemented countermeasure for individuals upon return to Earth or other partial gravity environments following microgravity exposure. The mechanism responsible for this occurrence appears to be related to a generalized increase in arterial blood pressure.

GRANTS

This research project was funded by grants from the National Heart, Lung and Blood Institute HL-61388, HL-67422, HL-84072, as well as HL-082406.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author(s).