Standing upright challenges the cardiovascular system as the pull of gravity displaces about 70% of the circulating blood volume to below heart level, much of it to the compliant veins of the dependent limbs and the pelvic organs. In patients with autonomic failure due to neurodegenerative diseases, the normal cardiovascular adjustments to this challenge are impaired, and symptomatic orthostatic hypotension becomes a common risk on standing or even sitting quietly. These patients learn to sway and shift, so that the pumping action of the muscles can be utilized to counter gravitational displacement of blood by squeezing venous blood from the legs upward. Augmentation of venous return in the upright posture can also be achieved by deliberate tensing of lower limb and abdominal muscles [1, 2], as depicted in Fig. 1.
These clinical observations were the basis for physical countermeasures, which are taught to patients with autonomic failure to combat symptomatic orthostatic hypotension [3-5]. Physical counterpressure manoeuvres specifically generate a counterpressure to oppose gravitational venous pooling (e.g. a single bout of lower-body muscle contraction to translocate blood centrally and sustained tensing of the same muscles to prevent subsequent peripheral pooling in the legs and abdomen). More recently, it has been shown that physical counterpressure manoeuvres are also effective interventions in otherwise healthy subjects with episodic orthostatic syncope due to neurally mediated (i.e. vasovagal reactions) [6, 7] or postexercise syncope .
In this narrative review, we will primarily consider these physical counterpressure manoeuvres. Secondarily, we will describe the broader category of physical countermeasures that include breathing manoeuvres and other physical methods, to oppose orthostasis. Existing external devices, which operate through some of the same physiological principles as these manoeuvres, will only be discussed for proof of principle.
The defining characteristic of the manoeuvres described in this review is the fact that they can be employed by patients when a faint is imminent. This is in contrast to devices such as bandages and abdominal belts, which require ongoing use to be effective. We will discuss both early studies in patient with primary autonomic failure due to neurodegenerative diseases, as well as more recent experience obtained in patients with neurally mediated syncope. The physiology and pathophysiology of orthostatic blood pressure control and perfusion of the brain are key factors in understanding how physical countermeasures work. These topics have been reviewed extensively [2, 9-12] and will only be discussed here briefly.
Physical counterpressure manoeuvres
It has been reported that intramuscular pressure is related to orthostatic tolerance . Henderson et al. demonstrated that intramuscular pressure measured in the relaxed biceps muscle was decreased after prolonged bed rest (38%), following surgery (35%), during voluntary hyperventilation (28%) and in the absence of air movement over the skin (31%) [13, 14]. These conditions are strongly associated with decreased orthostatic tolerance and a tendency to faint [2, 15]. In addition, intramuscular calf pressure has been shown to be 15–24 and 6–9 mmHg, respectively, in those without and with a tendency to faint during the head-up tilt test using a tilt table with a saddle and suspended legs (Fig. 1) .
Although these interesting results from studies performed in the 1930s and early 1940s have never been confirmed, it is highly likely that any increase in muscle tension will function to augment intramuscular pressure. Intramuscular pressure can be thought of as a pressure opposing that within the veins. As such, venous distension is determined by the difference in the opposing pressures on each side of the venous wall (i.e. the venous transmural pressure). Increasing pressure outside the vein will therefore reduce venous distension, displacing blood back towards the heart .
During quiet standing, the body behaves more or less as an inverted pendulum that sways about the ankles. The static increase in tone of the antigravity muscles that are involved in maintaining upright posture also function to oppose venous pooling in lower limb veins, thereby protecting central blood volume, i.e. the amount of blood available for the heart to pump [13, 14, 17-19].
It is considered that postural sway during quiet standing is able to compensate for otherwise poor orthostatic tolerance [20, 21]. Along these lines, Amberson  suggested the possibility of a connection between arterial baroreceptors and skeletal muscle tone, which could serve to increase muscle tensing during orthostasis. Although the precise neural pathway has not been established , recent work by Bernardi et al. demonstrated that carotid baroreflex modulation influences postural sway .
The first reports of the application of skeletal muscle tensing to prevent fainting reactions were from psychologists interested in the prevention of fainting reactions due to haemophobia. In the 1980s Öst and Sterness reported that ‘applied tension’ could be used as a behavioural method for treatment of this phobia , but the physiological mechanisms underlying its effect remained poorly understood due to the lack of haemodynamic measurements. However, the development in the early 1990s of the Penaz-Wesseling volume-clamp method, combined with the computation of stroke volume by pulse wave analysis, commercially available as the Finapres device, enabled clinical researchers to combine the experiences of individual patients with continuous noninvasive measurements of beat-by-beat changes in arterial pressure [25, 26]. As a result, the underlying haemodynamics of a wide range of movements that simulated every day activities could be investigated, first in patients with symptomatic orthostatic hypotension due to autonomic failure [1, 3] and in recent years as a countermeasure to avert an impending vasovagal faint. Single case reports were published at first [1, 27-31]. Figure 2 shows an example of such work, in which the combination of leg crossing and leg muscle tensing is effective in counteracting an impending vasovagal syncope .
Further evidence came from a study by Krediet et al., which included 20 patients . This work confirmed that the combination of leg crossing and leg muscle tensing depicted in Fig. 2 is highly effective. A rise in blood pressure was observed in all 20 subjects, and the vasovagal reaction was averted in five of these individuals. The remaining 15 subjects were able to postpone the faint by an average of 2.5 min. Patients who could completely abort the faint started the manoeuvre at a significantly higher blood pressure level than those patients who could not (79/51 vs. 61/41 mmHg). In a study focusing on the underlying haemodynamic mechanism, Krediet et al.  demonstrated that physical counterpressure manoeuvres such as leg crossing, muscle tensing, squatting and the crash position are effective against vasovagal reactions solely through increases in cardiac output as shown in Fig. 3.
During the manoeuvres involving muscle tensing, cardiac output increased by a factor of 1.3–1.7 from the low levels during presyncope and was restored to 95–104% of the stable values recorded in the head-up position in the first few minutes of tilt . Systemic vascular resistance responses varied, but remained largely unchanged. Because lower-body muscle tensing is accompanied by a threefold increase in leg blood flow , a counteracting presumably reflex-mediated vasoconstriction must occur in other parts of the circulation, such as the nonworking muscle, kidney and splanchnic vascular beds.
The rise in cardiac output during muscle tensing is largely attributed to mechanical and not to autonomic effects. The change in cardiac output as produced by leg crossing with muscle tensing is strikingly similar to that which is produced by inflation of an antigravity suit, which is similarly effective at aborting an impending vasovagal faint (see Fig. 4) . This reinforces the notion that the physiological effects of muscle tensing are mainly mechanical.
However, an instantaneous increase in heart rate (see Figs 2 and 3) was also observed during muscle tensing. This indicates that autonomic effects are present as well. The instantaneous increase in heart rate at the onset of muscle tensing is a reflex effect produced by a combination of the muscle mechanoreflexes and central command with inhibition of cardiac vagal tone . Such chronotropic changes at the onset of exercise are generally associated with concurrent increases in cardiac contractility, which may contribute to the increased cardiac output .
It is worth noting that forceful arm tensing manoeuvres, i.e. hand gripping at maximal voluntary force using a rubber ball and arm tensing by gripping one hand with the other and abducting both the arms at the same time [7, 36, 37], are also effective if they are accompanied by whole-body muscle tensing and thereby by an increase in cardiac output. Isometric arm exercises without tensing of large lower-body muscle groups are far less effective and cannot prevent an impending vasovagal faint [6, 38].
Activation of the muscle venous pump of the legs during tiptoeing or walking, in the presence of competent venous valves, pumps blood back to the heart and partially restores cardiac filling pressure. The leg muscle pump can be considered as a ‘second heart’  and is capable of translocating blood against a substantial pressure gradient (e.g. >90 mmHg). Manoeuvres that use skeletal muscle pumping are heel raises (i.e. plantar flexion; rising on the toes using calf muscles to raise heels off the floor) and repeated knee flexion (i.e. marching in place) [4, 16, 39]. However, their effects on standing blood pressure in patients with autonomic failure vary. The variable responses may stem from differences in the degree of sympathetic vasomotor failure in these patients [40, 41].
Knowledge that bending forward can mitigate orthostatic hypotension dates back to the 1930s  i.e. to the time of the first description of patients with idiopathic orthostatic hypotension in the English literature by Bradbury and Eggleson.
It is a useful manoeuvre for patients with autonomic failure to increase blood pressure in the upright posture, as has been reported by many investigators [1, 41, 43] and is shown in Fig. 5.
The beneficial effect of bending forward in patients with autonomic failure can be ascribed to pronounced abdominal compression and to lowering the head to heart level. Abdominal compression squeezes blood from the compliant splanchnic venous pool towards the heart, resulting in an increase in cardiac output and thereby in arterial pressure [44, 45]. Additionally, lowering the head to heart level shortens the hydrostatic column between the heart and the brain instantaneously by 25–30 cm corresponding to a hydrostatic pressure increase of 15–20 mmHg in mean blood pressure .
In patients prone to vasovagal syncope, bending forward is also reported to be a useful manoeuvre to increase orthostatic tolerance. Treatment of fainting patients traditionally consists of lowering the head between the knees whilst sitting (Fig. 6) [46-49]. Likewise, bending forward with hands on knees appears to be a preferred position for many athletes during recover from vigorous physical activity.
The beneficial effect of leg crossing in patients with autonomic failure (Fig. 7) [1, 43, 50, 51] has been attributed to mechanical compression of the veins in the legs, buttocks and abdomen, which displaces gravitationally pooled blood towards the heart and increases thoracic blood volume [39, 52, 53]. This results in an increase in cardiac filling pressure, stroke volume and cardiac output, effectively correcting the symptom-causing reductions in systemic arterial pressure and cerebral blood flow.
When leg crossing is practiced routinely, standing systolic/diastolic blood pressure can be increased by ~20/10 mmHg in patients with autonomic failure [3, 4, 9, 39, 43]. Even such a small rise in upright blood pressure may be clinically important, as it may shift mean arterial pressure from just below to just above the critical level of perfusion of the brain . Larger increases of ~30/15 mmHg can be seen when leg crossing is combined with the additional tensing of the leg musculature, thighs and buttocks.
Leg crossing improves orthostatic tolerance in healthy subjects as well as in patients with vasovagal fainting [27, 54-56]. When standing for prolonged periods, healthy humans who have a tendency to faint often unknowingly utilize this leg crossing countermeasure (i.e. the ‘cocktail party posture’ serves a physiological purpose).
By sitting down, the orthostatic load due to gravitational displacement of blood is decreased, resulting in increases in venous return, stroke volume and cardiac output and thereby blood pressure is increased [57, 58]. Portable chairs have been shown to be quite useful for patients who are severely incapacitated by their orthostatic symptoms . We have shown that the beneficial effect of sitting is greater, i.e. blood pressure increases more, when using lower portable chairs . A chair height of about 40 cm may be optimal for many patients, being effective in raising blood pressure and yet not so low as to cause difficulty in rising, although this may be more of a concern for patients with neurodegenerative diseases with motor disability [9, 59]. Leg crossing can increase seated systolic blood pressure considerably in patients with autonomic failure (Fig. 7) [5, 60, 61], whereas the effects in healthy normotensive subjects (on average <2 mmHg) and patients with hypertension (on average <7 mmHg) are small . Cheshire has reported an interesting phenomenon, observed in six patients with autonomic failure, of an urge to produce leg movements in the sitting position; these movements were effective at increasing seated blood pressure. This ‘hypotensive akathisia’ appeared to be habitual and could be transiently suppressed, yet felt irresistible to the patients .
Squatting, which is a combination of sitting, bending and increased muscle tone, expresses blood out of the leg venous vessels, thereby rapidly restoring venous return, cardiac filling pressure and cardiac output (Fig. 6) [33, 63, 64]. The temporary hindrance to blood flow to the legs caused by physical compression or kinking of blood vessels is thought to increase systemic vascular resistance mechanically as well, but this issue is debated . There are two varieties of the squatting posture. In the first, the body is vertical, with the weight resting on the balls of the feet and/or the toes and with the calves strongly pressed against the back surface of the thighs. In the second, the body is inclined forward, with the feet flat on the floor. The latter is reported to have a stronger effect in most subjects , but might be considered difficult by the less athletic. It is worth noting that the greater the amount of blood pooled in the lower limbs, the more robust the effect of squatting . In patients with autonomic failure, squatting is a useful manoeuvre when syncope is imminent  as it increases blood pressure and cerebral blood flow almost instantaneously (Fig. 7). It can produce an increase in systolic and diastolic blood pressure of about 60 mmHg and 35 mmHg, respectively, in these patients [1, 4, 9].
Squatting is also very effective for aborting an imminent vasovagal faint (Fig. 6). Suspension with a double-strop device imitating squatting is used as a position that secures venous return during helicopter rescue transportation . A drawback of squatting is that patients may have difficulty in returning to standing from this position. They may experience orthostatic lightheadedness due to a rapid fall in pressure during the transition [67-70]. This fall in pressure occurs primarily because of the sudden increase in blood flow to the legs due to vasodilatation of resistance vessels as the result of the brief large muscular effort to stand up from squatting, with widening of the local arterial–venous pressure gradient and removal of the physical hindrance of blood flow to the legs (reactive hyperaemia) as additional factors . The accelerative force during standing up from squatting may play an additional role . The fall in pressure upon arising from squatting can be exacerbated if the patient strains during the transition thereby decreasing venous return and further reducing stroke volume and cardiac output . Muscle tensing, such as clenching the buttocks or immediately walking upon standing, may reduce this problem (Fig. 8) [68, 69].
The beneficial effects of sitting in a knee-chest position [46, 49, 72] or placing one foot on a chair whilst standing [46, 73] are comparable to squatting (Fig. 7). It is clear that lying down (preferably with raised legs) is also a very effective intervention in case of an impending orthostatic faint .
Effects of breathing manoeuvres
Although the main focus of this review is the physical counterpressure manoeuvres that directly oppose gravitational venous pooling, it is worth discussing several breathing-related physical countermeasures that appear to indirectly benefit cardiovascular stability in the upright individual via action on the respiratory pump.
Intrathoracic and intra-abdominal pressures demonstrate counterpoised oscillations with breathing, such that intrathoracic pressure decreases during inspiration whilst intra-abdominal pressure increases. This pumps blood towards the heart through the abdominal region during inspiration, as veins in the iliac and femoral veins prevent retrograde flow out of the abdomen when this region is compressed by inspiratory efforts. The negative intrathoracic pressure further facilitates venous return from the abdomen, as well as augmenting return from the upper limbs and head . The large oscillations in peripheral venous return to the heart that are generated by this respiratory pump are buffered during normal breathing by the splanchnic circulation, as the hepatic vein is compressed to the point of occlusion by the diaphragm during inspiration, but in turn will release pooled blood during expiration when the vein is decompressed . The net result is that preload on the heart is somewhat enhanced during inspiration, but still maintained during expiration with normal breathing. With rib-cage-only breathing, intra-abdominal pressure no longer rises with inspiration, and the primary effect is augmented venous flow into the thorax during inspiration .
It appears that humans are ‘wired’ to take advantage of this respiratory pump during orthostatic challenge, as deep inspirations and sighs are common precedents to faints and may serve to augment venous return. Such sighs and gasps may also promote vasoconstriction and venoconstriction in the skin . Indeed, recent findings by Lucas et al. suggest that slow deep breathing in the absence of hyperventilation may improve orthostatic tolerance .
Negative-pressure breathing and inspiratory resistance
Manipulation of intrathoracic pressure, designed to take advantage of the action of the endogenous respiratory pump, can be affected by changing breathing patterns and breathing resistances. Early work by Weissler et al. demonstrated that negative-pressure breathing (inspiring and expiring against a slight vacuum of 16–19 mmHg) was an effective means to reverse or protect against experimentally induced orthostatic vasovagal syncope . More recent refinement of this concept has been the development of an impedance threshold device (ITD) for treatment of severe haemorrhage and as an adjunct to cardiopulmonary resuscitation, CPR. In spontaneously breathing subjects, this commercially available device prevents inspiration until a negative pressure of 7 cmH2O (~5 mmHg) has been generated at the mouth by greater inspiratory effort, and thus creates a more negative intrathoracic pressure during the inspiratory phase, but with minimal effect on expiration.
In healthy subjects, use of an ITD has been shown to increase tolerance to simulated haemorrhage (lower-body negative pressure) , increase orthostatic tolerance during free standing , reduce orthostatic hypotension during a squat/stand test  and increase tolerance to upright tilt following 1 min of all-out sprinting on a cycle ergometer against a high resistance , as illustrated in Fig. 9. The use of an ITD also has been shown to be beneficial in subjects with a tendency towards vasovagal syncope) . In patients with autonomic failure, use of an ITD augments standing blood pressure by ~8 mmHg . The notion that this additional circulatory pump is under volitional control prompted the study of other manoeuvres, without the use of a device, including inspiratory sniffing and inspiration through pursed lips. However, responses across patients were more variable than with the ITD, as the voluntary breathing manoeuvres sometimes resulted in concomitant hypocapnia and hypotension, due to inadvertent hyperventilation. Hypocapnia causes vasodilatation in skeletal muscle and vasoconstriction in the brain and can induce syncope in patients with autonomic failure [84, 85]. Thus, voluntary inspiratory sniffing and inspiration through pursed lips can also reduce orthostatic hypotension with the important caveat that hyperventilation must be avoided . This highlights the importance of training and feedback in the use of many countermeasures.
It is worth noting that use of inspiratory resistance, either by means of a device or by breathing through pursed lips, may generate additional benefits beyond the primary effects on venous return. Along these lines, it appears that inspiring against resistance resets the operating point of the arterial baroreflex towards higher pressures, akin to what happens during exercise. This may provide an advantage for defending against hypotension. It has also been suggested that inspiratory resistance may increase cerebral blood flow independent of changes in arterial pressure. From animal studies, it is clear that breathing against an inspiratory resistance will lower intracranial pressure , which is inversely related to cerebral vascular resistance owing to the Starling resistor effect. In addition, negative intrathoracic pressures may augment cerebral blood flow via a siphon effect, although the presence of a functional cerebral siphon in upright humans remains controversial (as discussed by Lacewell et al. ). Further refinements related to purposeful slow deep breathing  or use of rib-cage-only versus diaphragmatic breathing need to be explored .
Physical countermanoeuvres: from single observations and small series to clinical trials
When physical countermanoeuvres were applied in the early small, open-design patient series (n = 19–29) under conditions of daily living, excellent outcomes were reported during long-term follow-up (6–21 months) [6, 7, 36]. Next, the multicentre PC trial was performed , in which patients were recruited in 15 medical centres worldwide. The PC trial included 223 patients, aged 16–70 years, with recurrent vasovagal syncope (at least three episodes in the past 2 years, or at least one syncopal spell and at least three presyncopal episodes in the past year, and recognizable symptoms). The trial assessed the effect of adding physical counterpressure manoeuvres (either arm tensing or leg crossing) to conventional therapy (explanation of underlying mechanisms of vasovagal syncope, lifestyle modification advice using an information leaflet). There was a 36% relative risk reduction for syncope in the physical counterpressure group versus conventional therapy (Fig. 10). It should be noted that 35% of the patients did not have sufficiently long prodromes to benefit from the manoeuvres. The relative risk reduction of 36% is amongst the largest seen in a randomised controlled trial of any therapy for vasovagal syncope.
In the study by Croci et al., counterpressure manoeuvres were not effective in patients >65 years of age ; however, the number of patients involved was small and, under laboratory conditions, the pressor effect of muscle tensing in fit elderly subjects is at least as great as in young subjects . Squatting was not part of the counterpressure manoeuvres in the PC trial, but its great effectiveness under laboratory conditions is clear. Thus, an additional large prospective randomized controlled trial is not needed .
Teaching physical countermanoeuvres
The subtle but significant effects of physical counterpressure manoeuvres, such as leg crossing or squatting, on a low standing blood pressure are difficult to monitor by sphygmomanometer. A continuous (ambulatory) noninvasive blood pressure device, such as Finapres [25, 26], enables quantification of their effects in detail. The changes in blood pressure can be demonstrated immediately to a patient by showing the finger blood pressure tracing on a video screen in the doctor's surgery. This biofeedback will demonstrate to patients the effectiveness of their manoeuvres and will also help to select effective manoeuvres and to relate symptoms to actual blood pressure readings. Patients can thereby practise applying the manoeuvre effectively whilst being coached, possibly by a specialist nurse practioner [4, 32].
Physical countermanoeuvres often need to be modified specifically for individual patients depending on their abilities. They may be hard to perform in patients with multiple system atrophy. In the elderly, crossing the legs and pressing them together may lead to destabilisation, causing them to fall over. However, the buttock-clenching manoeuvre is often possible in the elderly . In our experience, this manoeuvre is effective to combat initial orthostatic hypotension.
Patients should be instructed in how to perform muscle tensing without raising intrathoracic pressure, as raising intrathoracic pressure impedes venous return to the heart and may cause blood pressure to drop and lead to lightheadedness in patients with neurogenic orthostatic hypotension . Patients should also be advised to avoid deep breathing and consequent hypocapnia during physical manoeuvres, because hypocapnia causes vasodilatation in skeletal muscle and vasoconstriction in the cerebral vessels both in patients with autonomic failure and in those with a tendency to vasovagal fainting [84, 85, 89]. Close observation whilst practising the manoeuvres may be useful to alert patients to this habit.
A great advantage of physical countermanoeuvres is that they can be applied instantaneously at the moment of symptomatic low upright pressure. They thereby give the patient the opportunity to regain self-confidence in provocative situations. Gradual exposure to specific provocative conditions may be of use to regain self-confidence. Patients may benefit from practising leg and lower-body muscle tensing whilst standing motionless each morning as part of their daily routine . A video demonstrating useful counterpressure manoeuvres and illustrating the direct effect they have on blood pressure is available on the patient website www.stars.org.uk.
We have found the following practical patient recommendations to be helpful (Table 1). First, apply leg crossing or skeletal muscle pumping using heel raises or marching in place as a preventive measure. Leg crossing has the advantage that it can be performed casually without much effort and without drawing attention to oneself. With proper instruction and practice, many patients will begin to automatically apply leg crossing in daily life to prevent the feeling of lightheadedness or faints during quiet standing. Leg crossing can also be used to prevent these symptoms in the sitting position in patients with reflex syncope (Wieling and Krediet, unpublished observations).
Table 1. Practical patient recommendations for manoeuvres to increase low blood pressure on standing
A video with instructions for patients and additional lifestyle measures for patients with orthostatic intolerance can be found at www.syncopedia.org and www.stars.org.uk, respectively.
Skeletal muscle pumping using heel raises or marching in place
Combatting symptomatic orthostatic hypotension
Leg muscle or buttock clenching
Whole-body muscle tensing, e.g. with arm tensing
Skeletal muscle pumping using heel raises or marching in place
Slow deep breathing
Combatting initial orthostatic hypotension
Emergency countermeasure in case of an impending faint
Bending over as if to tie shoe laces
Sitting with head between the knees (crash position)
Lying down with raised legs
Secondly, when leg crossing is insufficient to prevent symptoms, patients can try adding leg muscle tensing and buttock clenching. Whole-body muscle tensing, for example with arm tensing by gripping one hand with the other and abducting both the arms at the same time, can also be used. Buttock clenching is also very effective to combat orthostatic hypotension upon standing (initial orthostatic hypotension).
Finally, squatting, which is the most effective physical manoeuvre to increase blood pressure, can be used as an emergency measure to prevent losing consciousness when fainting symptoms develop rapidly. Likewise, bending over as if to tie shoe laces has similar effects to squatting and is simpler to perform by elderly patients [1, 18]. When arising again from the squatted position, patients should immediately sit down or begin lower-body muscle tensing to prevent the return of symptoms (Fig. 8 ).
The beneficial effect of physical countermeasures, based on the keen observations of astute clinicians in the first half of the 20th century, is an excellent example of how therapies that help many patients may be based on clinical observations in small groups or even individual patients [90, 91]. In summary, physical countermeasures are simple, inexpensive techniques that have a strong biological rationale based on experiments conducted in the physiology laboratory. These techniques can be applied instantaneously at the moment of symptomatic low upright pressure. Furthermore, they are clinically effective evidence-based interventions without side effects that improve quality of life in patients with orthostatic intolerance.