- The combination of dehydration, hyperthermia, and strenuous whole-body exercise poses a marked challenge to human cardiovascular control.
- This physiological strain is typified by reductions in cardiac output (Q̇), arterial blood pressure, and active muscle, brain, and skin blood flow during exercise approaching aerobic capacity.
- Although dehydration also reduces stroke volume and arterial blood pressure at rest and during isolated-limb exercise, limb blood flow and Q̇ are maintained or elevated in parallel to elevations in heart rate, whereas limb muscle aerobic metabolism remains unaltered.
- However, dehydration-induced reductions in peripheral blood flow impair tissue oxygen supply and active muscle but not brain metabolism during exhaustive whole-body exercise.
- Regional and systemic hemodynamics therefore differentially are affected by dehydration and hyperthermia depending on the magnitude of physiological stress imposed by exercise. How fluid- and thermosensitive mechanisms influence the functioning of the human brain, heart, skin, and muscles across exercise domains warrants investigation.
Editor's note: Go online to view the Journal Club questions in the Supplemental Digital Content: seehttp://links.lww.com/ESSR/A34.
Whole-body dehydration, associated with reductions in plasma, interstitial, and intracellular volume, generally occurs when people exercise for prolonged periods without fluid replacement. The progressive fall in total body fluid poses a marked challenge to thermoregulation and cardiovascular control. This is because dehydration attenuates sweat rate and skin blood flow (25,42) and reduces active muscle and systemic blood flow and mean arterial pressure (11,14,15,23), which result in significant increases in rate of body heat storage, core hyperthermia, and physiological strain. A compromised active muscle perfusion when dehydrated or hyperthermic has been implicated as an important factor in the chain of events leading to eventual fatigue because of its negative impact on oxygen supply (11,12). Based on an earlier series of investigations (11,14,15), previously discussed in this journal (7), our related findings from recent work indicate that the detrimental effects of dehydration and hyperthermia are not necessarily uniform among the tissues of the human body and across a range of exercise intensities and modalities (36,44,47,48). Our current hypothesis is that the cardiovascular challenge of dehydration, evident during strenuous whole-body exercise, does not occur at rest, during isolated muscle group exercise, or low-intensity whole-body exercise. Moreover, essential tissues of the human body (e.g., the brain) are still susceptible to the combined cardiovascular challenge of dehydration and exhaustive exercise but seem to be better able to defend their metabolism in the face of compromised oxygen delivery than active skeletal muscle.
Throughout this article, and unless otherwise stated, the term “dehydration” is referred to as a loss of body fluids (e.g., equivalent to a body mass loss of ~3%–5%) in combination with elevations in body core temperature (hyperthermia). This is because many of the studies in the literature induced dehydration through prolonged exercise in the heat. For reference, studies invoking hyperthermia without dehydration are presented and distinguished from those combining body hyperthermia and dehydration, respectively. The primary data presented in this review are from studies investigating the impact of dehydration and concomitant hyperthermia on physiological function in young, healthy, trained men undertaking knee-extensor and cycling exercise. Comparable cardiovascular data currently are limited for other population groups (e.g., young untrained, older trained and untrained, and women); however, it is reasonable to suggest that the physiological principles, explored subsequently, also would be applicable to those populations.
DEHYDRATION CHALLENGES CARDIOVASCULAR FUNCTION DURING STRENUOUS EXERCISE
Dehydration and concomitant core hyperthermia, accrued progressively during prolonged submaximal exercise in the heat, lead to increases in heart rate and total peripheral resistance, arterial hemoconcentration, small reductions in blood volume and mean arterial pressure, and marked reductions in stroke volume and cardiac output (Q̇) and active and nonactive limb, skin, and cerebral blood flow (CBF) (Fig. 1) (7,11,14,15,23). Importantly, these circulatory responses are prevented completely when dehydration and hyperthermia are offset by regular oral rehydration (14,15,23) or when dehydrated individuals exercise in a cold environment, where the core-to-skin temperature gradient increases and the excessive rise in body core temperature is prevented (14,16,22). Without dehydration, substantial core and internal hyperthermia impairs regional and systemic blood flow during exercise close to aerobic capacity (12,46) but not during moderate-intensity exercise (27,29). Thus, the impact of dehydration on cardiovascular function and aerobic performance is most prevalent when large water losses are coupled with hyperthermia during prolonged exercise (4,14,15,31). In the following sections, we explore whether the physiological strain invoked by the combination of dehydration and hyperthermia is consistent among the tissues of the human body and across a range of exercise modalities.
DEHYDRATION AND SYSTEMIC BLOOD FLOW
A progressive fall in Q̇ is a common feature of the dehydration-induced cardiovascular strain observed during prolonged, strenuous whole-body exercise in the heat (Fig. 1) (7). Concomitant to the declining Q̇, heart rate rises continuously, whereas stroke volume declines by approximately 30% (14,15), with the latter equally and additively influenced by the loss in blood volume and the rise in core body temperature and heart rate (10,15). Contrastingly, hyperthermia alone does not compromise stroke volume and Q̇ is significantly elevated (40,45). These differential findings suggest that compromised systemic blood flow is dependent on the extent of the cardiovascular challenge induced by combined stress evoked by dehydration, hyperthermia, and exercise. To provide support for this notion, recent findings from our laboratory explored the impact of progressive dehydration on central hemodynamics, at rest and during exercise of a low physiological load (isolated-limb exercise) (44). Progressive dehydration reduced blood volume (~5%) and lowered stroke volume (~20 mL) to a similar degree to that seen in the whole-body exercise paradigm. The fall in stroke volume was coupled to a substantial fall in end-diastolic volume, with only a small fall in end-systolic volume, and a marked elevation in heart rate (~30 bpm) compared with control (hydrated) values. Interestingly, however, and in contrast with whole-body exercise, Q̇ was maintained from rest to exercise among the hydration manipulations. Thus, it seems that the extent of the total muscle mass recruited, and by extension the physiological demands of the exercise, plays an important role in determining the cardiovascular strain induced by dehydration.
Factors Contributing to the Fall in Stroke Volume With Dehydration
Stroke volume is determined by intrinsic factors within the heart itself (i.e., cardiac contractility) and extrinsic factors associated with alterations in preload (i.e., venous return) and afterload (i.e., arterial blood pressure). Recent investigations have shed some light into the contribution of these mechanisms on the dehydration-induced stroke volume reduction. It seems that at rest and during exercise of a low cardiovascular demand, when Q̇, mean arterial pressure, systemic vascular resistance, cardiac ejection fraction, and left ventricle (LV) mechanics are stable, the reduction in stroke volume is unrelated to functional changes in left ventricular function (44). Measures of systolic twist and basal rotation velocity (e.g., LV mechanics) largely are maintained or somewhat enhanced by dehydration (44), similar to findings during intermittent, submaximal exercise (9). It remains to be seen whether more substantial body-mass losses, in combination with more prolonged, high-intensity exercise, negatively affect left ventricular function; some evidence has suggested depressed regional strains, torsion, and untwisting velocity in the presence of an enhanced Q̇, after an ultraendurance activity inducing a body mass loss of approximately 4.5% (30). It is likely that the intensity and duration of exercise and the magnitude of dehydration influence the LV responses during and after exercise. The lack of effect of dehydration at rest and low-intensity exercise (44), however, supports the notion that altered LV mechanics are unlikely to play a major role in the stroke volume reduction with dehydration. Another intrinsic factor, which could contribute to the reduction in stroke volume with dehydration, is the progressive reduction in cardiac filling time secondary to the increase in heart rate. The increase in heart rate is a response to reduced blood volume and elevations in core temperature and neuroadrenal sympathetic activity (7,15). The contribution of cardiac tachycardia on the reduced stroke volume with dehydration is supported by the observation that raising heart rate, by right atrial pacing, leads to reductions in stroke volume at any given exercise intensity (24). Therefore, the combination of strenuous exercise, dehydration, and core hyperthermia heightens systemic sympathetic activity that further increases heart rate, reducing cardiac filling time and compounding the fall in stroke volume.
However, measures of mean arterial pressure and LV volumes afford discussion of the role of extrinsic factors in the stroke volume decline. Augmented afterload is not a factor because progressive dehydration lowers arterial pressure (15). Instead, the diminished LV end-diastolic volume and lowered femoral beat volume (Fig. 2) indicate that venous return is compromised in conditions of dehydration (Fig. 3). The lower blood volume and the enhanced peripheral vasoconstriction are two factors associated with the lesser venous return. Granted the close circuit nature of the cardiovascular system and the multiple mechanisms involved in cardiovascular regulation make it difficult to establish the cause-and-effect relation among the aforementioned factors, evidence indicates that venous return and tachycardia are contributing to the stroke volume decline with dehydration at rest and during exercise.
DEHYDRATION AND LIMB BLOOD FLOW
The skeletal muscle circulation mirrors the varied central hemodynamic alterations, due to dehydration, at rest and during isolated-limb and strenuous whole-body exercise. At rest, limb vascular conductance and limb blood flow (LBF) are enhanced with progressive dehydration, a response maintained during small muscle mass exercise, despite substantial body mass losses (~3.5%) and reductions in limb perfusion pressure (Fig. 4) (36). Conversely, during prolonged, whole-body exercise, the substantial fall in stroke volume (47 mL·beat−1) and Q̇ (~4 L·min−1) is coupled to an approximately 2 L·min−1 reduction in LBF versus control exercise (11). The marked fall in active limb perfusion during whole-body exercise is offset when fluid intake matches fluid loss (11,28) and when central hemodynamics are normalized by exercising in a supine or semirecumbent position, despite marked body hyperthermia (27,29). Collectively, these studies highlight that the LBF and central hemodynamic responses to dehydration are coupled, such that reductions in LBF are only seen when Q̇ declines.
What Mechanisms Explain the Different Leg Blood Flow Responses?
A number of putative mechanisms might explain these divergent limb hemodynamic responses to dehydration under resting and different exercise conditions. At rest, the dehydration-induced elevation in limb vascular conductance and LBF (Fig. 4) likely is related in part to thermosensitive mechanisms, responding to changes in internal and local tissue temperature, similar to that observed during local and whole-body passive heating (5,6,19,37). The disparate LBF responses to small muscle mass and whole-body exercise could be related to alterations in either perfusion pressure or local vascular conductance. In this regard, the increase in LBF seen in small muscle mass exercise must be due to net local vasodilation, because mean arterial and limb perfusion pressure is suppressed (36). Furthermore, systemic sympathetic activity was only slightly elevated on the transition from rest to exercise, among the full range of dehydration conditions (e.g., circulating noradrenaline increased from 1 to a peak of 2 nmol·L−1). During whole-body prolonged exercise, a similar fall in mean arterial pressure (~8%) was seen, but circulating catecholamines markedly were elevated (~18 nmol·L−1). Nevertheless, increased sympathetic vasoconstrictor activity did not explain the fall in active-limb perfusion, because vascular conductance was essentially unchanged or slightly enhanced (11,36). However, the progressive decline in Q̇ and perfusion pressure accounts for most of the reduced end-exercise LBF. This observation is similar to those seen during constant-load, maximal exercise with superimposed body hyperthermia (12). Thus, during strenuous whole-body exercise, reductions in Q̇ and mean arterial pressure are related to the fall in active-muscle perfusion with dehydration.
DEHYDRATION AND CBF
The findings from our recent studies indicate that the cardiovascular strain induced by dehydration also has consequences for the cerebral circulation. Regional and global CBF increases on the transition from rest to moderate-intensity exercise (20,35), remaining stable throughout the duration of moderate-intensity exercise (33). However, if exercise intensity progresses beyond approximately 60% V˙O2max, or when constant load exercise is performed in an uncompensable hot environment, CBF is suppressed toward or below baseline levels (33,41). Our experimental findings indicate that dehydration, concomitant to an elevated body core temperature (~1°C), further enhances the cerebrovascular strain by reducing CBF to a similar end-exercise value, equivalent to control conditions, but at a substantially reduced absolute work rate (~270 vs ~340 W), during whole-body cycling exercise (Fig. 5) (48). This advancement of the fall in CBF was not present before dehydration, or after 1 h of recovery with full fluid replenishment, where CBF dynamics were restored to those in the control exercise bout. The independent effect of dehydration was confirmed further when the same participants recorded CBF dynamics comparable with that observed in the control and rehydration tests, during three similar graded exercise bouts, performed on the same day, while fully hydrated. As outlined in Figure 1, the deleterious impact of dehydration on CBF is not isolated to short-duration incremental exercise. We found that during approximately 2 h of prolonged submaximal exercise, without regular fluid ingestion, CBF progressively was suppressed, whereas blood flow to other vessels across the head (e.g., the common- and external-carotid arteries) was comparable with those seen during prolonged exercise while hydrated (47). The dehydration-induced suppression of CBF during prolonged submaximal exercise is similar to the decline seen with substantial elevations in body core temperature (32,33). It is apparent therefore that dehydration compromises CBF during strenuous prolonged and maximal incremental exercise to volitional exhaustion.
How Does Dehydration Reduce CBF?
Numerous mechanisms, acting independently or synergistically, are purported to regulate the CBF response to exercise (34). Like other vascular beds, perfusion of the cerebral circulation depends on the balance between perfusion pressure and local vascular conductance; it is, however, unlikely that mean arterial pressure per se accounts for the changes in cerebral perfusion during exercise (43). However, and consistent with the available literature, strenuous exercise is coupled to a fall in cerebrovascular conductance, concomitantly to elevations in internal temperature and reductions in the carbon dioxide tension in arterial blood (PaCO2) (47,48); the latter a potent substance invoking both vasodilation (increase PaCO2) and vasoconstriction (decrease PaCO2) across the cerebral circulation (50). Of note, in our present manipulations of hydration status, was that body core temperature was elevated (~1°C) when dehydration developed during prolonged, submaximal and maximal incremental exercise, versus control (hydrated) exercise. It has been shown that body hyperthermia induces nonmetabolic hyperventilation (49) that in turn lowers PaCO2 and CBF (3,26,33,38); restoring PaCO2, while hyperthermic, restores cerebral hemodynamics, even with high levels of minute ventilation (21,26). Thus, dehydration promotes body hyperthermia and decreases CBF, at least in part by a hyperthermic-hyperventilatory reduction in PaCO2.
DEHYDRATION-INDUCED REDUCTIONS IN PERFUSION CAN AFFECT TISSUE AEROBIC METABOLISM
Dehydration can reduce aerobic exercise performance (4) and aerobic work capacity (31). Central to the onset of fatigue in both scenarios is the high internal and skin temperatures and the aforementioned, exercise-dependent, reductions in regional and systemic blood flow (Fig. 6). Reduced tissue blood flow (and O2 delivery), in the absence of enhanced O2 extraction, can suppress tissue aerobic metabolism. However, as discussed subsequently, this physiological strain does not affect different tissues equally and may not be present during low- or moderate-intensity exercise.
Consequences of Altered Blood Flow for Active-Limb Muscle Metabolism
An important function of the cardiovascular system during exercise is to match active muscle O2 delivery to metabolic demand (1,8,17,18). Manipulation of arterial O2 content (CaO2) leads to concurrent and reciprocal changes in LBF and Q˙ that preserve limb aerobic metabolism, indicating an important role of O2 sensing pathways in blood flow regulation (17). As such, despite the dehydration-induced fall in LBF during prolonged whole-body exercise, limb O2 delivery and aerobic metabolism are, for the most part, maintained due to a widening of the arterial-venous O2 difference and arterial hemoconcentration (11). At rest and during isolated-limb exercise, with a stable limb aerobic metabolism, a small hemoconcentration induced by dehydration might be expected to be accompanied by a reduced LBF. However, both LBF and CaO2 were elevated by dehydration and possibly the effect of exercise per se (36). Because our LBF measures did not discriminate between the different tissues of the limb (e.g., the skin, bone, and muscle), the uncoupling between LBF and CaO2 is likely due to pathways sensing other stimuli such as local tissue and core temperature. Notwithstanding, the differing LBF responses at rest and during small and large muscle mass exercise are met by reciprocal alterations in O2 content and extraction that maintains active muscle aerobic metabolism. However, under intense physiological load (severe exercise, high skin and core temperatures, and substantial dehydration), these adjustments may not compensate for the fall in limb O2 delivery (12).
Reduced CBF Does Not Impair Global Cerebral Metabolism
A relevant question is whether this circulatory challenge to the brain is conducive to a compromised cerebral tissue metabolism. It has been suggested that reductions in CBF impair cerebral oxygenation, which might contribute to fatigue during strenuous exercise (39). However, our experimental work indicates that the cerebral metabolic rate for oxygen (CMRO2) remains remarkably stable across a range of hydration states, exercise intensities, and rest-to-exercise transitions (Fig. 5). Reciprocal elevations in O2 extraction served to compensate for the approximately 18% fall in CBF (13,47,48). Although we acknowledge that global measures of CMRO2 are an imperfect assessment of regional cerebral metabolism (and metabolism of other substrates), and that it remains theoretically possible that substantial reductions in CBF (to the order of >50%) could compromise cerebral oxygenation (2,43), the stable aerobic metabolism of the brain suggests that other circulatory factors (e.g., LBF) play a greater role in the compromised whole-body exercise capacity when dehydrated.
Our model highlights that progressive exercise-induced dehydration, with concomitant hyperthermia, can lead to impaired perfusion to multiple regional tissues and organs. However, the extent of the impact of dehydration on physiological function depends on the level of dehydration, the exercise intensity, and the ambient environmental conditions. Blood flow through the heart, active muscles, and brain is elevated with dehydration at rest and during isolated-muscle or low-intensity exercise. However, during strenuous or prolonged whole-body exercise (>60% V˙O2max), brain, active muscle, and systemic blood flow is compromised, mechanistically associated to an enhanced vasoconstrictor activity, suppressed venous return, and cardiac filling. The fall in regional and systemic perfusion has differing effects on tissue metabolism. However, reductions in active muscle blood flow, which are not compensated fully by elevations in O2 extraction when exercise requires aerobic capacity or close to it, are a likely precursor to early fatigue. Future research should address how fluid- and thermosensitive mechanisms influence the functioning of the human brain, heart, skin, and muscles across exercise domains. Additional research is needed to quantify the limits of the circulatory adjustments across the human brain, among a wider range of hydration and temperature manipulations, to explore any possible association with the onset of fatigue.
The dehydration and hyperthermia studies conducted at the Centre for Human Performance, Exercise and Rehabilitation, Brunel University London, were funded by the Gatorade Sports Science Institute, PepsiCo Inc, USA.
The primary studies contained within this manuscript were supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA. The views contained within this document are those of the authors and do not necessarily reflect those of PepsiCo Inc.
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