Physical countermeasures to increase orthostatic tolerance

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. From 2; reproduced with permission. 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 8. 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. It has been reported that intramuscular pressure is related to orthostatic tolerance 2. 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) 16. 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 2. 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 22 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 2, recent work by Bernardi et al. demonstrated that carotid baroreflex modulation influences postural sway 23. 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 24, 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 32. From 32; reproduced with permission. Further evidence came from a study by Krediet et al., which included 20 patients 6. 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. 33 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. From 33; reproduced with permission. 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 33. Systemic vascular resistance responses varied, but remained largely unchanged. Because lower-body muscle tensing is accompanied by a threefold increase in leg blood flow 34, 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) 35. This reinforces the notion that the physiological effects of muscle tensing are mainly mechanical. From 35; reproduced with permission. 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 26. 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 33. 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’ 2 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 42 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. From 1; reproduced with written informed consent of the patient and permission from the publisher. 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 11. 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. From 49; reproduced with permission. 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. From 32; reproduced with written informed consent from the patient and permission from the publisher. 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 10. 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 59. We have shown that the beneficial effect of sitting is greater, i.e. blood pressure increases more, when using lower portable chairs 60. 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 62. 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 to be and could be yet to the patients 5. which is a combination of bending and increased muscle tone, blood of the leg venous thereby venous return, cardiac filling pressure and cardiac output (Fig. 6) The to blood flow to the legs by physical compression or of blood is thought to increase systemic vascular resistance as but this is are of the squatting In the the body is with the on the of the the toes and with the strongly against the back of the In the the body is with the on the The is reported to have a effect in subjects but be considered by the less It is worth noting that the the amount of blood pooled in the lower the more the effect of squatting In patients with autonomic failure, squatting is a useful manoeuvre when syncope is as it increases blood pressure and cerebral blood flow instantaneously (Fig. It can produce an increase in systolic and blood pressure of about mmHg and mmHg, respectively, in these patients 1, 4, is also effective for aborting an vasovagal faint (Fig. with a squatting is used as a position that venous return during A of squatting is that patients may have difficulty in to standing from this may experience orthostatic due to a in pressure during the This in pressure primarily of the increase in blood flow to the legs due to of resistance as the of the large to from with of the pressure gradient and of the physical of blood flow to the legs as additional factors The force during standing from squatting may an additional The in pressure from squatting can be if the patient during the thereby venous return and stroke volume and cardiac output 11. tensing, such as the buttocks or standing, may reduce this (Fig. From reproduced with permission. The beneficial effects of sitting in a position or one on a chair whilst standing are to squatting (Fig. It is that with is also a effective in case of an impending orthostatic faint Although the of this review is the physical counterpressure manoeuvres that oppose gravitational venous it is worth physical countermeasures that to cardiovascular in the upright individual action on the and pressures with such that pressure during whilst pressure This pumps blood towards the heart through the abdominal during as veins in the and veins prevent flow of the when this is by The pressure venous return from the abdomen, as well as return from the limbs and head 2. The large in peripheral venous return to the heart that are by this pump are during normal breathing by the splanchnic circulation, as the vein is to the of by the during but in will pooled blood during when the vein is The is that on the heart is during but during with normal pressure with and the primary effect is venous flow the during It appears that humans are to of this pump during orthostatic as and are common to and may serve to augment venous Such and may also vasoconstriction and in the skin recent by et al. that breathing in the absence of hyperventilation may orthostatic tolerance of pressure, to of the action of the can be by breathing and breathing work by et al. demonstrated that breathing and against a of mmHg) was an effective to or against orthostatic vasovagal syncope 35. More recent of this has been the development of an for treatment of and as an to In breathing subjects, this commercially available a pressure of 7 mmHg) has been at the by and a more pressure during the but with effect on In healthy subjects, use of an has been shown to increase tolerance to simulated increase orthostatic tolerance during standing reduce orthostatic hypotension during a test and increase tolerance to upright tilt following of on a against a resistance as in Fig. The use of an also has been shown to be beneficial in subjects with a tendency towards vasovagal In patients with autonomic failure, use of an standing blood pressure by mmHg The notion that this additional pump is control the study of other manoeuvres, without the use of a device, and through However, responses patients were more variable than with the as the voluntary breathing manoeuvres in and due to in skeletal muscle and vasoconstriction in the brain and can syncope in patients with autonomic failure voluntary and through can also reduce orthostatic hypotension with the that hyperventilation must be This the of and in the use of many It is worth noting that use of by of a or by breathing through may generate additional the primary effects on venous Along these lines, it appears that against resistance the of the arterial baroreflex towards higher to during This may an for against It has also been suggested that resistance may increase cerebral blood flow of changes in arterial pressure. From it is that breathing against an resistance will lower pressure which is related to cerebral vascular resistance to the In addition, pressures may augment cerebral blood flow a although the presence of a cerebral in upright humans discussed by et al. Further related to breathing or use of breathing to be When physical were in the early patient conditions of were reported during 6, 7, the was performed in which patients were in 15 The included patients, with vasovagal syncope in the 2 or at one and at in the and The the effect of physical counterpressure manoeuvres arm tensing or leg to of underlying mechanisms of vasovagal syncope, using an was a risk for syncope in the physical counterpressure (Fig. It be that of the patients not have to from the manoeuvres. The risk of is the seen in a of any for vasovagal syncope. From reproduced with permission. In the study by et al., counterpressure manoeuvres were not effective in patients years of the of patients involved was small the effect of muscle tensing in subjects is at as as in subjects was not of the counterpressure manoeuvres in the but its conditions is an additional large is not The but effects of physical counterpressure manoeuvres, such as leg crossing or on a low standing blood pressure are to by A continuous noninvasive blood pressure device, such as Finapres 25, of their effects in The changes in blood pressure can be demonstrated to a patient by the blood pressure on a in the This will to patients the of their manoeuvres and will also to effective manoeuvres and to symptoms to blood pressure Patients can thereby the manoeuvre effectively whilst being by a 4, 32. Physical often to be specifically for individual patients on their may be to in patients with system In the crossing the legs and may to to However, the manoeuvre is often in the 3. In this manoeuvre is effective to combat orthostatic Patients be in how to muscle tensing without raising pressure, as raising pressure venous return to the heart and may cause blood pressure to and to in patients with orthostatic hypotension 11. Patients also be to breathing and during physical manoeuvres, in skeletal muscle and vasoconstriction in the cerebral both in patients with autonomic failure and in those with a tendency to vasovagal fainting whilst the manoeuvres may be useful to patients to this A of physical is that they can be instantaneously at the of symptomatic low upright pressure. thereby the patient the to in to conditions may be of use to Patients may from leg and lower-body muscle tensing whilst standing each as of their 32. A useful counterpressure manoeuvres and the effect they have on blood pressure is available on the patient We have the following patient to be leg crossing or skeletal muscle pumping using heel raises or marching in as a Leg crossing has the that it can be performed without much and without to and many patients will to leg crossing in to prevent the of or during quiet Leg crossing can also be used to prevent these symptoms in the sitting position in patients with reflex syncope and when leg crossing is to prevent patients can leg muscle tensing and muscle tensing, for example with arm tensing by gripping one hand with the other and abducting both the arms at the same can also be is also effective to combat orthostatic hypotension standing orthostatic which is the effective physical manoeuvre to increase blood pressure, can be used as an to prevent when fainting symptoms Likewise, bending over as if to has similar effects to squatting and is to by patients 1, When from the patients or lower-body muscle tensing to prevent the return of symptoms (Fig. The beneficial effect of physical countermeasures, on the observations of in the first of the is an example of how that many patients may be on clinical observations in small groups or even individual patients In physical countermeasures are that have a on in the physiology These can be instantaneously at the of symptomatic low upright pressure. they are clinically effective interventions without side effects that of in patients with orthostatic are of