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. 2009 Nov 2;587(Pt 24):5959–5969. doi: 10.1113/jphysiol.2009.179549

Influence of age on syncope following prolonged exercise: differential responses but similar orthostatic intolerance

Carissa Murrell 1,2, James D Cotter 2, Keith George 3, Robert Shave 4, Luke Wilson 1, Kate Thomas 1, Michael J A Williams 5, Tim Lowe 6, Philip N Ainslie 7
PMCID: PMC2808552  PMID: 19884316

Abstract

Orthostatic tolerance is reduced with increasing age and following prolonged exercise. The aim of this study was to determine the effect of age on cardiovascular and cerebrovascular responses to orthostatic stress following prolonged exercise. Measurements were obtained before, and within 45 min after, 4 h of continuous running at 70–80% of maximal heart rate in nine young (Y; 27 ± 4 years; Inline graphic 59 ± 10 ml kg−1 min−1) and twelve older (O; 65 ± 5 years; Inline graphic 46 ± 8 ml kg−1 min−1) athletes. Middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound), blood pressure (BP; Finometer) and stroke volume (SV) were measured continuously whilst supine and during 60 deg head-up tilt for 15 min or to pre-syncope. Orthostatic tolerance was reduced post-exercise (tilt completed (min:s, mean ±s.d.): Pre, 14:39 ± 0:55; Post, 5:59 ± 4:53; P < 0.05), but did not differ with age (P > 0.05). Despite a 25% higher supine MCAv in the young, MCAv at syncope was the same in both groups (Y: 34 ± 10 cm s−1; O: 32 ± 13; P > 0.05). Although the hypotensive response to syncope did not differ with age, the components of BP did; SV was lowered more in the young (Y: –57 ± 16%; O: –34 ± 13%; P < 0.05); and total peripheral resistance was lowered in the older athletes but was unchanged in the young (Y: +8 ± 10%; O: –21 ± 12%; (at 10 s pre-syncope) P < 0.05). Despite a lower MCAv in the older athletes, time to syncope was similar between groups; however, the integrative mechanisms responsible for syncope did differ with age. The similar MCAv at pre-syncope indicates there is an age-independent critical cerebral blood flow threshold at which syncope occurs.

Introduction

Syncope in athletes following prolonged exercise is widely reported (Gratze et al. 2005; Murrell et al. 2007) and is a consequence of an inability to maintain adequate cerebral perfusion. Orthostatic stress transiently reduces arterial blood pressure (BP). Normally this drop in BP is restored via the arterial baroreflex, which increases heart rate (HR) and systemic vascular resistance, thereby helping to maintain cerebral blood flow (CBF). An important protective feature of the cerebral circulation is the ability to maintain a relatively stable CBF over a wide range of mean arterial blood pressures (MAP; ∼60–140 mmHg) by altering cerebrovascular resistance; a process termed cerebral autoregulation (Franco Folino, 2007). Experimental studies indicate that blood flow velocity in the middle cerebral artery (MCAv; an index of CBF) is also dependent on cardiac output (Inline graphic) (Ide et al. 1998; Ogoh et al. 2005).

Vasovagal syncope is the most common form of neurally mediated syncope. It is an autonomic reflex which results in an increase in vagal activity and the withdrawal of sympathetic tone, causing bradycardia and hypotension. Once BP falls below the lower limit of autoregulation, and oxygen extraction is maximized, further cerebral vasodilatation cannot maintain sufficient flow to maintain consciousness, and syncope ensues (Franco Folino, 2007). Following prolonged exercise, the adoption of an upright posture challenges the cardiovascular system. Post-exercise hypotension combined with venous pooling in vasodilated vessels reduces venous return and consequently Inline graphic (Halliwill, 2001). Related to this, reduced transmission of sympathetic activity into systemic vascular resistance has been observed following moderate (Halliwill et al. 1996) and prolonged exercise (Murrell et al. 2007), limiting the ability to maintain MAP and ultimately cerebral perfusion. A further mechanism which may exacerbate the development of syncope following prolonged exercise is continued hyperventilation-induced hypocapnia and related cerebral vasoconstriction (Lucas et al. 2008).

The incidence of syncope increases with ageing, especially in individuals older than 65 years (Tan & Parry, 2008). Baroreflex sensitivity and the HR response to orthostasis are also reduced (Laitinen et al. 2004), contributing to the lowered orthostatic tolerance. Cerebral autoregulation appears to be unaffected by ageing (Van Beek et al. 2008); however, a reduced basal CBF may provide an explanation for the increased incidence of syncope with age. No studies have documented whether there is a differential age-related elevation in syncope incidence following prolonged exercise. The purpose of this study was to assess the CBF response to orthostatic stress in young and older athletes following prolonged exercise. We examined the hypothesis that older athletes would be more orthostatically intolerant following prolonged exercise than their younger counterparts.

Methods

Subjects and ethical approval

Nine young (18–35 years) and twelve older (60–80 years; Table 1) trained runners volunteered for this study which was approved by New Zealand's Lower South Region Ethics Committee, and complied with the Declaration of Helsinki. Subjects were informed of the experimental procedures and potential risks involved in the study before their written consent was obtained. Subjects were not taking any cardiovascular medications, all were non-smokers, and none had any history of cardiovascular, cerebrovascular or respiratory disease, or a prior diagnosis of orthostatic hypotension. None reported frequent recurrent episodes of syncope and/or related symptoms.

Table 1.

Participant characteristics

Young Older
Males:females 7:2 10:2
Age (years) 27 ± 4 65 ± 5 *
Height (cm) 179 ± 10 173 ± 8
Body mass (kg) 72.0 ± 9.0 71.6 ± 7.6
BMI (kg m2) 22.3 ± 1.6 23.9 ± 2.4
Inline graphic (ml kg−1 min−1) 59.0 ± 9.6 45.5 ± 7.7 *
Training (h week−1) 8 ± 3 8 ± 4
Years competing in endurance events 4 ± 2 27 ± 9 *
Endurance events completed in lifetime (n) 6 ± 3 (range 2−10) 111 ± 88 * (range 20−250)
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Values are means ±s.d. based on 9 young and 12 older subjects. BMI, body mass index; Inline graphic, maximal oxygen consumption.

*

Different from young (P < 0.05).

Experimental protocol

Subjects were required to report to the laboratory on three occasions. Prior to inclusion into the study all subjects were screened by means of a thorough medical history, chest auscultation and 12-lead ECG. If left ventricular hypertrophy, murmur or significant arrhythmia were detected, subjects underwent a clinical transthoracic echocardiogram to exclude overt pathology. Following successful screening, subjects underwent familiarization to the laboratory and testing procedures before completing a maximal aerobic capacity (Inline graphic) test. Subjects were requested to abstain from alcohol for 12 h before, and from caffeine for 4 h before, the Inline graphic and main testing protocols. Subjects were also instructed to arrive well hydrated by consuming 1000 ml of water on the evening before and 500 ml on the morning of testing. On arrival at the laboratory for the main session, subjects voided their bladder prior to having height and mass recorded. Following ∼30 min supine rest, subjects completed head-up tilt (HUT) to 60 deg for 15 min or to syncope. We instructed participants to indicate when they were experiencing pre-syncopal symptoms of dizziness/light-headedness, nausea etc. and wished to be returned to the supine position. The result of this symptom-dependent, rather than BP-dependent cessation of HUT means that in most cases BP fell to low levels. These criteria permitted a detailed determination of the haemodynamic changes associated with syncope. Typical signs and symptoms of impending circulatory collapse were also closely monitored. To limit the effect of the skeletal muscle pump, subjects were instructed not to make any muscle contractions at rest or during the tilt. After baseline (pre-exercise) testing, following a ∼30 min warm-up (at 70–80% of maximal HR) participants completed 4 h of continuous running at 70–80% of maximal HR on a flat course. During this time, HR was continuously displayed and recorded (Polar S610i monitors, Polar, Finland). The above protocol was then repeated within 20 min of exercise completion (post-exercise).

CBF velocity, arterial BP and heart rate

Blood flow velocity in the right middle cerebral artery (MCAv) was measured using a 2 MHz pulsed Doppler ultrasound system (DWL Doppler, Sterling, VA, USA). Beat to beat BP was measured using finger photoplethysmography (Finometer, TPD Biomedical Instruments, The Netherlands). In addition, following 5–10 min of supine rest, manual BP recordings were obtained intermittently to confirm the accuracy of the finger photoplethysmography measurements. From the blood pressure waveform, HR, stroke volume (SV) and cardiac output (Inline graphic) were calculated using the ModelFlow method which incorporates sex, age, height and mass data (BeatScope 1.0 software; TNO; TPD Biomedical Instruments). This method provides a reliable estimate of changes in Inline graphic in healthy humans at rest, during exercise (Sugawara et al. 2003) and during 70 deg HUT (Jellema et al. 1996). Heart rate was measured by 3-lead ECG. All data were sampled continuously at 200 Hz using an analog–digital converter (Powerlab/16SP ML795; ADInstruments, Colorado Springs, CO, USA) interfaced with a computer. Data were later analysed (Chart version 5.4.2, ADInstruments). Total peripheral resistance (TPR) was estimated as MAP/Inline graphic. An index of cerebrovascular resistance (CVR) was estimated from MAP/MCAv.

Cerebral and muscle oxygenation

Oxygenation was measured using near infrared spectroscopy ((NIRS) NIRO-200; Hamamatsu Photonics KK; Hamamatsu, Japan). A probe holder containing an emission probe and detection probe was attached to the right side of the forehead with a distance of 5 cm between probes (Ferrari et al. 2004). For assessment of muscle oxygenation, optodes were positioned on the middle portion of the right vastus lateralis muscle at the mid-thigh level and parallel with the long axis of the muscle. Similar to the brain, the optodes were housed in an optically dense plastic holder secured on the skin with tape to minimize extraneous light. In the brain and muscle, local oxygenation was measured simultaneously every 1 s throughout the experiment, and expressed as the change from the initial value. NIRS enables the assessment of dynamic changes in the oxygenation state of the underlying tissue which ultimately reflect changes in tissue metabolism, blood flow and oxygen extraction (Ferrari et al. 2004).

Respiratory gas exchange

During each session, subjects breathed through a leak-free respiratory mask (Hans-Rudolph 8980, Kansas City, MO, USA), attached to a one-way non-rebreathing valve (Hans-Rudolph 2700). End-tidal partial pressures of CO2 and O2, Inline graphic and Inline graphic, were sampled from the leak-free mask and measured using gas analysers (model CD-3A (CO2) and model S-3A/I (O2), AEI Technologies, Pittsburgh, PA, USA). Changes in Inline graphic adequately reflect those of arterial CO2 (Inline graphic), especially in the hypocapnic range (Thomas et al. 2009).

Haematological/urinary variables

Following at least 20 min supine rest, a venous blood sample was procured, without stasis, for immediate analysis of haematocrit and haemoglobin concentration in triplicate to allow the estimation of changes in plasma volume. Blood samples were then spun immediately and the plasma removed and frozen for later analysis. Plasma adrenaline and noradrenaline were extracted using the aluminium oxide technique and analysed using high-performance liquid chromatography with electrochemical detection. Hydration status was estimated in duplicate from urine specific gravity (Hand refractometer, Atago, Tokyo, Japan).

Statistical and data analysis

Data were averaged over the 3 min baseline period immediately preceding HUT, and during the final 60 s prior to imminent syncope during HUT. All data were analyzed using SPSS statistical software (SPSS version 17.0, SPSS Inc., Chicago, IL, USA). To assess the mean difference between young and older subjects at baseline, independent-samples t tests were used. To evaluate the effect of exercise and age on physiological changes whilst supine and during HUT, repeated-measures ANOVA was conducted for age (between-subjects factor) and time (repeated factors: pre- and post-exercise; supine and pre-syncope). To assess changes in MCAv relative to changes in putative variables, we used (i) correlations of ΔMCAv vs.Δpredictor variable from supine to syncope, and (ii) multiple linear regression to assess the effect of ΔMCAv vs.Δpredictor variables collectively (i.e. Inline graphic, SV, MAP and Inline graphic). Statistical significance was established at an α level of 0.05, and data are expressed as means (±s.d.).

Results

Exercise

All athletes completed the 4 h of exercise. The young athletes covered 41 ± 4 km, while the older athletes completed 36 ± 6 km (P < 0.05), and distance covered was related to Inline graphic (r2= 0.65, P < 0.01). Food and fluid were consumed ad libitum (mean fluid consumption: 1.5 ± 0.5 l). Body mass was reduced in both groups post-exercise (−2.2 ± 0.6 kg (young); −2.8 ± 0.7 kg (older); P < 0.01 vs. pre-exercise), although to a greater extent in the older athletes (P < 0.05). Plasma volume was reduced post-exercise (−3.1 ± 5.6%; P < 0.05), but was not different with age. Urine specific gravity was elevated following exercise (1.013 ± 0.009 (pre-exercise); 1.020 ± 0.008 (post-exercise); P < 0.05 vs. pre-exercise) but was unchanged with age. Average daily ambient temperature across the 13 days of the study was 14.7 ± 2.1°C (range: 11.8–19.9°C), with 72 ± 8% relative humidity (range: 60–83%).

Syncope

Following the 4 h of exercise, syncope developed in 17 of the 21 subjects during HUT, compared with 3 (1 young, 2 older) of the 21 athletes pre-exercise. Data from the 4 subjects (2 young, 2 older) who did not reach syncope post-exercise were excluded from all syncope analysis. These athletes did not exhibit obvious differences in post-exercise physiological alterations when compared with their orthostatically intolerant counterparts. Duration of HUT was reduced post-exercise (min:s, 5:59 ± 4:53) relative to pre-exercise (14:39 ± 0:55; P < 0.05); this reduction did not differ with age (P > 0.05; Fig. 1) and was unrelated to Inline graphic (r2= 0.00, P > 0.05).

Figure 1.

Figure 1

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Survival curve of time to syncope during 15 min head-up tilt to 60 deg in young and older athletes following 4 h of running at 70–80% maximal HR

Age and supine haemodynamics

Supine MCAv was lower (mean: −24%; systolic: −21%; diastolic: −32%) and CVR higher (46%) in the older group prior to exercise (P < 0.01 vs. young; Table 2). Mean arterial BP, systolic BP and TPR were higher (10%, 13% and 30%, respectively) and muscle oxygenation lower (−5%) in the older group pre-exercise (P < 0.05 vs. young). In the older athletes, Inline graphic was slightly elevated and Inline graphic reduced when compared to the young athletes prior to exercise (P < 0.05).

Table 2.

Steady-state supine cardiovascular and cerebrovascular measures in young and older athletes prior to and following 4 h of running at 70–80% maximal HR

Young
 Older
Pre-exercise Post-exercise Pre-exercise Post-exercise
Cardiovascular
HR (beats min−1) 63 ± 6 81 ± 10 † 57 ± 6 75 ± 9 †
MAP (mmHg) 84 ± 5 79 ± 7 † 92 ± 5 * 84 ± 7 †
SBP (mmHg) 123 ± 9 113 ± 13 † 139 ± 10 * 121 ± 14 †
DBP (mmHg) 65 ± 4 61 ± 5 † 68 ± 3 65 ± 4 †
SV (ml) 112 ± 15 95 ± 20 † 103 ± 17 80 ± 18 †
Inline graphic (l min−1) 7.0 ± 1.4 7.6 ± 1.2 5.9 ± 1.1 5.8 ± 1.3
TPR (mmHg l−1 min−1) 12.5 ± 2.7 10.5 ± 1.0 † 16.2 ± 2.9 * 14.8 ± 2.6 †
Cerebrovascular
MCAv (cm s−1) 66 ± 6 76 ± 12 † 50 ± 9 * 52 ± 9 †
SMCAv (cm s−1) 108 ± 13 120 ± 20 85 ± 16 * 84 ± 14
DMCAv (cm s−1) 47 ± 8 53 ± 7 † 32 ± 6 * 39 ± 10 †
CVR (mmHg cm−1 s−1) 1.31 ± 0.12 1.07 ± 0.22 † 1.91 ± 0.32 * 1.66 ± 0.25 †
Respiratory
Inline graphic (mmHg) 110 ± 4 107 ± 5 115 ± 3 * 114 ± 5
Inline graphic (mmHg) 42 ± 3 41 ± 5 † 38 ± 4 * 35 ± 6 †
Oxygenation index
Cerebral (%) 67.5 ± 5.0 70.6 ± 5.3 65.3 ± 6.3 65.6 ± 8.2
Systemic (%) 71.9 ± 4.1 73.2 ± 4.0 68.5 ± 3.2 * 67.0 ± 4.7
Haematological
Hb (mg dl−1) 14.2 ± 1.1 14.6 ± 1.0 14.5 ± 0.9 14.9 ± 1.0
Hct (%) 42 ± 3 43 ± 3 43 ± 3 43 ± 4
Adrenaline (pg ml−1) 20 ± 8 37 ± 13 † 17 ± 9 56 ± 30 †§
Noradrenaline (pg ml−1) 158 ± 39 283 ± 131 † 201 ± 67 571 ± 114 †§
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Values are means ±s.d. based on up to 9 young and 12 older subjects. Supine data were averaged over 3 min immediately prior to head-up tilt. HR, heart rate; MAP, mean arterial blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; SV, stroke volume; Inline graphic, cardiac output; TPR, total peripheral resistance; MCAv, middle cerebral artery blood flow velocity; SMCAv, systolic MCAv; DMCAv, diastolic MCAv; CVR, cerebrovascular resistance; Inline graphic, partial pressure end-tidal oxygen; Inline graphic, partial pressure end-tidal carbon dioxide; Hb, haemoglobin; Hct, haematocrit.

*

Different from young (P < 0.05);

†

different from pre-exercise;

§

differential alteration with exercise from young (P < 0.05).

Prolonged exercise and supine haemodynamics

Following exercise, MCAv was elevated (10 ± 17%; P < 0.01; Table 2). Systolic MCAv was unchanged (vs. pre-exercise), but diastolic MCAv was higher (19 ± 24%; P < 0.01) post-exercise, irrespective of age. Likewise, CVR was reduced post-exercise in both groups (P < 0.01). Heart rate was elevated, and MAP, systolic and diastolic BP, SV and TPR reduced following 4 h of exercise (P < 0.05), although age had no effect on these exercise-induced alterations. Inline graphic was reduced post-exercise (P < 0.01) but did not differ with age. Adrenaline and noradrenaline concentrations were elevated (P < 0.01) in both groups post-exercise, although the older athletes exhibited greater elevations in both (adrenaline: 110 ± 83% (young) vs. 295 ± 301% (older); noradrenaline: 94 ± 97%vs. 210 ± 98%; P < 0.05).

Haemodynamic alterations immediately prior to syncope

At impending syncope, MCAv was reduced in both the young and older athletes (Fig. 2). The reduction in MCAv with HUT was greater in the young (−43 ± 18 cm s−1vs.−22 ± 11 cm s−1 (older) at 10 s pre-syncope; P < 0.01). Interestingly, however, the absolute mean MCAv immediately prior to syncope was almost identical in both groups (34 ± 10 cm s−1 (young), 32 ± 12 cm s−1 (older) at 10 s pre-syncope; P > 0.05). Hypotension was apparent during HUT in both groups (P < 0.01), but did not differ with age (MAP: −42 ± 22% (young); −45 ± 13% (older) at 10 s pre-syncope; Fig. 3). The older athletes had an attenuated HR response to HUT (+14 ± 9 vs.+36 ± 19 beats min−1 (young) at 60 s pre-syncope; P < 0.01). However, immediately prior to syncope, the young athletes exhibited a drop in HR (−30 ± 26 beats min−1; P < 0.05), not observed in the older athletes. Stroke volume was reduced prior to syncope in both age groups, although to a greater extent in the young (−57 ± 16%vs.−34 ± 13% (older) at 10 s pre-syncope; P < 0.01 vs. supine). Cardiac output was reduced throughout the pre-syncope period in both the young and older athletes (−47 ± 19% (young); −34 ± 13% (older); P < 0.01 vs. supine). Total peripheral resistance was maintained pre-syncope in the young (8 ± 10% at 10 s pre-syncope; P > 0.05 vs. supine) but was reduced in the older athletes (−21 ± 12%; P < 0.01 vs. supine). Muscle oxygenation was lowered in the pre-syncope period in both the young and older athletes, although to a greater extent in the young (−18 ± 10%vs.−10 ± 7% (older) at 10 s pre-syncope; P < 0.05 vs. supine). Inline graphic was reduced pre-syncope in the young (−14 ± 7 mmHg at 10 s pre-syncope; P < 0.05 vs. supine), but did not differ from supine values in the older athletes (P > 0.05 vs. supine). Cerebrovascular resistance and cerebral oxygenation were mostly unchanged with age and in the pre-syncope period.

Figure 2. Absolute (left) and relative (right) postural changes in cerebral variables whilst supine and in the final 60 s prior to syncope in young and older athletes following 4 h of running at 70–80% maximal HR.

Figure 2

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▪, Young; ○, Older. MCAv (A), middle cerebral artery blood flow velocity; Inline graphic (B), end-tidal CO2; CVR (C), cerebrovascular resistance; and cerebral TOI (D), cerebral total oxygenation index. * Different from young (P < 0.05); † different from supine (young; P < 0.05); ‡ different from supine (older; P < 0.05).

Figure 3. Absolute (left) and relative (right) postural changes in cardiovascular variables whilst supine and in the final 60 s prior to syncope in young and older athletes following 4 h of running at 70–80% maximal HR.

Figure 3

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▪, Young; ○, Older. HR (A), heart rate; MAP (B), mean arterial blood pressure; SV (C), stroke volume; Inline graphic (D), cardiac output; TPR (E), total peripheral resistance; and muscle TOI (F), muscle total oxygenation index. * Different from young (P < 0.05); † different from supine (young; P < 0.05); ‡ different from supine (older; P < 0.05).

Discussion

We have conducted the first detailed experiment to examine the influence of ageing on the mechanisms of syncope following prolonged exercise. The three major findings of the study were : (1) there were no age-related differences in orthostatic tolerance following exercise; (2) despite a higher basal MCAv in the younger athletes, which was further elevated following exercise, MCAv at the point of syncope was similar between groups, equating to a 2-fold greater reduction in MCAv in the young; and (3) despite comparable hypotension at the point of impending syncope, there were age-related differential circulatory mechanisms underpinning this response.

Age and supine haemodynamics

As observed previously (Buijs et al. 1998), supine MCAv was higher in the young compared with the older athletes. This reduction in MCAv with ageing is probably due to a reduction in brain volume and therefore metabolism and blood flow (Pantano et al. 1984). Mean arterial BP, systolic BP, TPR and CVR were all elevated in the older group whilst supine, most probably due to the ageing-induced increases in sympathetic activity and reductions in vagal activity (Ferrari et al. 2003).

Prolonged exercise and supine haemodynamics

The effects of 4 h of exercise on cardiovascular and cerebrovascular haemodynamics were apparent irrespective of age. Despite a lowered Inline graphic, MCAv was elevated by 15% in the young and tended to be lower (4%) in the older athletes whilst supine following exercise. This increase in MCAv occurred independently of increases in Inline graphic, indicating that elevations in neuronal activity or cerebral metabolism are more likely to be responsible (Dalsgaard, 2006). Because the order of the study was randomized with young and older participants, and individualized and identical Doppler settings were used for each subject prior to and following exercise, it would seem unlikely that this finding is explained by technological error. Increases in systolic MCAv have been observed immediately following 6–8 min of dynamic heavy exercise (75–80% max HR) in young individuals (Ogoh et al. 2007); however, this elevation did not persist beyond 1–3 min. In the older athletes, there was little change in MCAv post-exercise, although Inline graphic was lowered at this time point. There is a ∼2–4% reduction in MCAv per mmHg reduction in Inline graphic (Kastrup et al. 1998; Peebles et al. 2007), which is maintained with healthy ageing. If MCAv was corrected for the post-exercise hypocapnia more evident in the older group (52 cm s−1 (uncorrected) to 55–57 cm s−1 (corrected)), the post-exercise elevation in MCAv in the older group would still only be half that observed in the young. The mechanism underlying these age-dependent changes in neurovascular coupling following exercise warrant further research.

Following exercise, in both the young and older athletes, elevations in HR and adrenaline and noradrenaline concentrations were apparent, indicating reductions in vagal activity and increases in sympathetic activity. Post-exercise hypotension was evident following exercise, with significant reductions in both systolic and diastolic BP and TPR. The magnitude of hypotension (∼10 mmHg) was unrelated to age or pre-exercise BP, although it was similar to that reported previously (Halliwill, 2001), supporting the notion that exercise duration has little effect on the magnitude of post-exercise hypotension (MacDonald et al. 2000).

Haemodynamic alterations immediately prior to syncope

In the young, at the point of syncope, MCAv was 54% lower than supine. Van Lieshout et al. (2003) have speculated that reductions in MCAv of at least 50% are required to induce syncope. However, in the older group, the reduction in MCAv at syncope (vs. supine) was only 41%. It should be noted that this critical limit has not been clearly shown, especially in an older population who already have a reduced CBF. Although supine MCAv was 32% higher in the young athletes following exercise, at the point of syncope MCAv was similar between the young and older athletes. This finding indicates that an absolute MCAv (irrespective of age), rather than a relative reduction in MCAv may be more important in the maintenance of cerebral perfusion and consciousness. The reticular activating system in the brainstem is responsible for maintaining consciousness. Since this structure undergoes little atrophy with increasing age (Luft et al. 1999), it seems plausible that to maintain consciousness the ‘older’ brain would require a similar blood flow to its younger counterpart.

An attenuated HR response to orthostasis, as apparent in the older group following exercise (Fig. 3), is a well established consequence of ageing, due collectively to a reduction in baroreflex sensitivity, an inability to withdraw vagal outflow, and a desensitization to elevations in sympathetic activity (Laitinen et al. 2004). Prior to syncope in the young group only, there was a precipitous drop in HR. This is an autonomic reflex whereby the final effect is an increase in vagal activity and a reduction in sympathetic drive (Franco Folino, 2007), typical of vasovagal syncope. Younger individuals tend to exhibit a bradycardic response immediately prior to syncope whereas in older individuals there is a greater hypotensive response (Kurbaan et al. 2003). Although there is no established link between exercise-induced cardiac dysfunction and syncope, it seems possible to suggest that the two could be related. One study found that desensitization of β-adrenergic receptors following 4 h of rowing contributed to an attenuated left ventricular systolic function (Hart et al. 2006), which ultimately could compromise CBF.

Although the extent of hypotension prior to syncope during HUT was similar in the young and older athletes, the determinants of MAP differed with age. In the young at pre-syncope during HUT, SV was reduced by approximately 50% compared with supine. Total peripheral resistance was maintained at supine levels, indicating that an inability to maintain venous return was the major cause of syncope in this group. Conversely, in the older group, TPR and SV were both reduced from supine values, indicating that impairments in both vasoconstriction and venoconstriction were responsible for syncope. At rest, sympathetic activity is under the control of the arterial and cardiopulmonary baroreflex; however, baroreflex sensitivity is reduced with increasing age (Laitinen et al. 2004). Although resting sympathetic activity increases with age, vasoconstrictor responses to the same level of sympathetic stimulation are reduced 10–15% in older individuals (Dinenno & Joyner, 2006). The inability of the older athletes to maintain TPR pre-syncope supports a reduced vasoconstrictive responsiveness to sympathetic stimulation with age (at least in the vasculature of the lower limb) (Dinenno & Joyner, 2006). Previous thoughts were that syncope is chiefly caused by hypotension owing to a fall in systemic vascular resistance (Schondorf & Wieling, 2000). Recently, this concept has evolved to the possibility that the hypotension may equally be caused by a precipitous fall in Inline graphic (Verheyden et al. 2008). Our findings in the younger athletes support this concept, as Inline graphic was compromised but TPR was maintained at syncope.

Reduced muscle oxygenation is an early indicator of central hypovolaemia during lower body negative pressure, indicating a limited SV, Inline graphic and supply of blood to skeletal muscle (Soller et al. 2007). The inverse relationship between muscle oxygenation and TPR indicates that peripheral vasoconstriction in response to central hypovolaemia is the major cause of the reduced muscle blood flow (Soller et al. 2007). Our data are consistent with this notion, as evidenced by greater reductions in muscle oxygenation and SV in the young. TPR was maintained in the young during HUT, indicating a greater vasoconstriction, in an attempt to increase central blood volume; however, pooling in venous capacitance vessels prevented this. The older athletes exhibited lesser reductions in muscle oxygenation, potentially due to an inability to constrict arterioles supplying skeletal muscle, as indicated by a reduction in TPR pre-syncope. Post-exercise reductions in thoracic blood volume and increases in thigh blood volume have been documented 2–3 h following 6 min of rowing at maximal intensity (Hanel et al. 1997). These data indicate that a redistribution of central blood volume to the periphery following exhaustive exercise, may contribute to post-exercise orthostatic intolerance. Madsen et al. (1995) observed that the reduction in muscle oxygenation due to vasoconstriction during early HUT was followed by an increase in muscle oxygenation as pre-syncopal symptoms appeared, due to the typical ‘vasovagal’ response. Our data did not display a marked increase in muscle TOI immediately prior to syncope, indicating that hypotension at syncope may equally be due to a reduced Inline graphic (Verheyden et al. 2008) as sympathetic nervous activity is not always withdrawn pre-syncope (Cooke et al. 2009).

Cerebral blood flow is maintained over a range of blood pressures; however, it has been established that CBF is also dependent on Inline graphic. The relationship between Inline graphic and MCAv has been shown both at rest and during exercise, with linear changes in MCAv in response to changes in Inline graphic (Ide et al. 1998; Ogoh et al. 2005). Our data indicate that reductions in MCAv were related to reductions in Inline graphic (along with MAP and SV) at syncope (Fig. 4). However, when data were analysed by multiple linear regression, changes in MCAv were accounted for by changes in SV alone, which will partly reflect lack of power for regression. Nonetheless, in view of SV being a major determinant of Inline graphic and especially its pulsatility (which would influence cerebrovascular dampening of changes in perfusion), this predictor may be partly responsible for the degree of cerebral hypoperfusion at the point of syncope. Despite lesser reductions in SV at syncope, the older athletes exhibited an increased sensitivity of changes in MCAv to changes in SV at this point (Fig. 4).

Figure 4. Relationship between relative changes in MCAv with changes in predictor variables from supine in the 10 s immediately prior to syncope in young and older athletes following 4 h of running at 70–80% maximal HR.

Figure 4

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▪, Young; ○, Older. MCAv, middle cerebral artery blood flow velocity; SV, stroke volume; Inline graphic, cardiac output; MAP, mean arterial blood pressure; and Inline graphic, end-tidal CO2. Although not displayed separately, the mean slope of ΔMCAv with ΔSV did differ with age (P < 0.05). Age had no effect on other variables.

Hyperventilation-induced hypocapnia and consequent reductions in MCAv at syncope have been well documented (Levine et al. 1994; Novak et al. 1998), and were apparent in our subjects at this point, independent of age (Fig. 4). Some studies have reported that the responsiveness of cerebral vessels to alterations in Inline graphic is reduced with age (Yamaguchi et al. 1979; Kastrup et al. 1998), which could reduce the onset of syncope as the fall in MCAv per unit change in Inline graphic is reduced. However, our data indicate similar percentage reductions in MCAv per mmHg change in Inline graphic of 4% (young) and 5% (older), indicating this ageing-induced reduction in cerebrovascular reactivity in response to changes in Inline graphic may either be altered following prolonged exercise, or absent in a highly active older population.

Considerations

Velocity vs. flow

We measure blood flow velocity in the middle cerebral artery by transcranial Doppler ultrasound. However, MCAv is a reliable and valid index of CBF (Giller et al. 1993; Serrador et al. 2000). Similarly, we also assume that changes in blood flow velocity are consistent between the major cerebral arteries.

Hydration

Hypohydration, by a reduction in blood volume, can reduce orthostatic tolerance (Davis & Fortney, 1997). Body mass was reduced in both the young and older participants following 4 h of running. However, loss of glycogen and intracellular water bound to glycogen is likely to contribute significantly to this body mass loss. Our data displayed no relationship between the change in plasma volume and tilt time completed, indicating that post-exercise hypohydration had no effect on time to syncope.

Sex

Orthostatic tolerance is reduced in females (Franke et al. 2003). However, regardless of age, the females (2 young and 2 older) in our study did not exhibit a lowered orthostatic tolerance when compared to their male counterparts. One study found that neither sex nor menstrual cycle phase affected post-exercise haemodynamics following 60 min of exercise (Lynn et al. 2007), indicating that any sex differences in orthostatic tolerance may be eliminated post-exercise.

In conclusion, orthostatic tolerance was not reduced to a greater extent in older athletes post-exercise. Despite a lower basal MCAv in the older athletes, MCAv at the point of syncope was similar to that in younger athletes, indicating that there may be an age-independent critical CBF threshold for syncope. Although the tilt-induced hypotension during pre-syncope was also similar between age groups, the circulatory mechanisms responsible for it differed with age. In the young, SV was reduced and TPR maintained pre-syncope, indicating that venous pooling led to an inability to maintain central blood volume. In the older athletes, a reduced SV was concomitant with a lowered TPR, indicating an inability to maintain both arterial and venous tone.

Acknowledgments

Funding for this study was provided by Sport and Recreation New Zealand (SPARC) and the Department of Physiology, University of Otago.

Glossary

Abbreviations

BP

blood pressure

CBF

cerebral blood flow

CVR

cerebrovascular resistance

HR

heart rate

HUT

head-up tilt

MAP

mean arterial blood pressure

MCAv

middle cerebral artery blood flow velocity

SV

stroke volume

TPR

total peripheral resistance

Author contributions

All authors contributed to the conception and design, or analysis and interpretation of data, the drafting of the article or revising it critically for important intellectual content, and the final approval of the version to be published. The experiments for this manuscript were completed in the Department of Physiology at the University of Otago.

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