Clinical REVIEW
Is there a role for contrast hydrotherapy?
Paul W Baker
Contrast hydrotherapy involves the immersion or dousing of a limb in alternating hot and cold water. This ‘tweaks’ the peripheral autonomic nervous system, altering vascular tone and flow and improving nitric oxide production and vessel health. It has been shown (Elmstahl et al, 1995; Fiscus et al, 2005) to improve both short- and long-term distal blood flow and claudication in patients with significant peripheral arterial disease, as the vascular and lymphatic system share many similarities with regards their genesis, vascular biology and autonomic innervation. This paper shows why contrast hydrotherapy may be a preventative treatment for lymphoedema.
vascular dysfunction is a more obvious being published in the last 10 years. This Key words cause of morbidity and mortality. Given explosion of knowledge is relevant to Contrast hydrotherapy emerging structural and functional the concepts presented in this paper, as interactions between the venous and it has provided the scientific evidence Lymphatic system lymphatic systems, and the pivotal role giving biological plausibility. Innervation Vascular biology The notion of why such a simple Given emerging structural Oedema and cost-effective therapy as contrast and functional interactions hydrotherapy may be a bona fide between the venous and treatment for lymphoedema was seeded lymphatic systems, and the by observations made in subjects lthough thousands of years pivotal role of the lymphatics at different ends of the spectrum of have passed since the first in immune function, lipid health and disease, namely athletes and patients with significant peripheral Adescriptions of lymph nodes absorption and maintenance in 500 BC, and lymph vessels in 300 arterial disease. Specifically, contrast BC (Ambrose, 2006), in relative of the interstitium, the hydrotherapy, and even thermal sauna terms the lymphatic system is still effects of lymphatic therapy, have been shown to improve poorly understood. Indeed, as noted dysfunction may be greater peripheral blood flow with long-term by Skandalakis et al (2007), 25 years than previously thought. improvements in vascular function ago the President of the International (Elmstahl et al, 1995; Imamura, 2001; Society of Lymphology (ISL) stated, Kihara et al, 2002; Fiscus et al, 2005). ‘It is perhaps rather unusual for an of the lymphatics in immune function, This is most likely through gentle international society to feel that it is lipid absorption and maintenance of stimulation of the autonomic nervous essential to draw attention to the very the interstitium, the effects of lymphatic system, with a subsequent change in existence of its subject matter… such dysfunction may be greater than sympathetic efferent activity to the is the general lack of knowledge about previously thought. peripheral vasculature. Evidence of the lymphatic system’. It seems that similarities between the endothelium our desire to understand the structure That said, in the last 20 years, our of the peripheral vasculature and that and function of its seemingly more scientific understanding of the structure, of lymphatic collecting vessels, with pathologically significant cousin, the function and physiology of the lymphatic regards to cell biology and autonomic vascular system, has taken precedence. system has grown considerably, as innervation, suggests that findings in Perhaps rightly so in light of the fact that evidenced by a literature search using the vascular system may apply to the Medline (going back to 1948) for articles lymphatics (Khaisman, 1982; Sjoberg and with either lymphatics or lymph(o) Stein, 1991; McHale, 1985, 1990, 1995; Paul W Baker is an Intensive Care Paramedic with the SA edema in the title. In this 62-year search van Helden and Zhao, 2000; van Helden Ambulance Service. He is currently an MBBS (candidate) at period, a little over half of the work in et al, 2006). Flinders University of South Australia, Bedford Park, this field has been published in the last South Australia 20 years, with around a third of all work This paper examines these findings
72 Journal of Lymphoedema, 2011, Vol 6, No 2
Baker.indd 2 07/12/2011 14:50 Clinical REVIEW
in the context of contrast hydrotherapy, Kneipp) has a long tradition in central ‘housekeeping’ of the interstitial space, and their relevance to the lymphatic Europe and is established in some forming lymph, a clear and colourless system and patients with lymphoedema. rehabilitative cardiological clinics for fluid, consisting of an ultrafiltrate of It also touches on recent evidence the adjunctive non-pharmacological plasma, proteins, white blood cells, showing that certain historical treatment of patients with cardiovascular and other particulate matter (Swartz, recommendations for the prevention disease and heart failure’. Indeed, a 2001; Ohtani and Ohtani, 2008; Juric and management of lymphoedema growing body of scientific evidence and Detmar, 2009). Postprandially, the have now been shown to be incorrect exists in the conventional literature (as lymphatic system is also involved in (Liu and Olszewski, 1993; Rymal, 2002; evidenced by Medline and Cochrane the absorption of dietary lipids and fat McKenzie and Kalda, 2003; Hayes et Summaries/Reviews) regarding the soluble vitamins (A, D, E and K) from al, 2009; Hayes, 2010; Kim et al, 2010; efficacy of hydrotherapy in the adjunct the gastrointestinal tract (Cueni, 2008). Rourke et al, 2010; Schmitz et al, 2010), Lymphatic dysfunction causes paving the way for well-controlled Hydrotherapy can be studies into the effect of contrast a build-up of protein-rich fluid in hydrotherapy. defined in lay terms as the interstitial space. Clinically, this ‘the use of water, either is referred to as lymphoedema, the What is hydrotherapy and is it taken internally or externally, to hallmarks of which are limb swelling, seriously by clinicians around the world? maintain health and prevent inflammation, hypertrophy of adipose To understand the concepts presented disease’ (Fine Life Wellness tissue and induration of the sub- and epifascial tissue. While it causes in this paper, it is first necessary to Spa, 2009). It is an age-old understand what contrast hydrotherapy pain, disfigurement, embarrassment, is and how it is used. In Europe in practice with reports dating depression and functional impairment particular, it is a respected treatment back to at least the time of (Lee et al, 2009), it can also cause for patients with cardiovascular disease Hippocrates, around 500 BC morbidity, due to compromised immune and heart failure, with Japanese studies (Greek Medicine, 2009). function and increased susceptibility validating its use (Imamura, 2001; Kihara, to infection (Mortimer, 1998; Rourke, 2002). The ability of hydrotherapy 2010). Lymphoedema is defined on the to ‘tweak’ homeostatic mechanisms management of an array of conditions basis of its aetiology as either primary pertaining to thermoregulation, by such as osteoarthritis, dermatitis, or secondary (Piller, 2003). Primary affecting peripheral autonomic activity psoriasis, ankylosing spondylitis, lymphoedema is due to congenital and vascular tone (Boron and Boulpeap, fibromyalgia and congestive heart failure. dysplasia in the lymphatic system, 2009), is thought to underpin its efficacy It is important to recognise however, usually a hypoplasia, resulting in reduced (Michalsen et al, 2003; Fiscus et al, 2005). that among this evidence (e.g. Merial- lymph transport. While there are many Kieny et al, 2011), there are few well- causes of secondary lymphoedema, Hydrotherapy can be defined in designed randomised controlled studies, in developed countries, it is most lay terms as ‘the use of water, either a factor that will hopefully be addressed commonly the result of treatment for internally or externally, to maintain health in the future. breast cancer (Rourke et al, 2010). and prevent disease’ (Fine Life Wellness Spa, 2009). It is an age-old practice Specifically, contrast hydrotherapy Of relevance to this discussion are with reports dating back to at least the involves the alternating immersion factors responsible for the movement time of Hippocrates, around 500 BC or dousing of the body, or parts of of fluid, electrolytes and protein into the (Greek Medicine, 2009). Hydrotherapy it, in warm (37–45°C) and then cold interstitial space, and their subsequent and communal baths were common (10–15°C) water, with the ratios of time removal by the lymphatics. Historically, practice in the Roman empire. At the fall spent in each varying considerably from based on a simplistic understanding and of the empire, this widespread practice study to study, and presumably depending interpretation of Starling’s hypothesis, wained due to dominance of more on the desired outcome (Cochrane, the majority of fluid filtered from conservative Christian views, especially 2004; Fiscus et al, 2005; Morton, 2007; capillaries into the interstitium was regarding nudity (Moore, 2008). In Vaile, 2008). A common trend is that the assumed to be reabsorbed at the venule central Europe in the eighteenth warm immersion is longer than the cold end of the capillary and subsequently and nineteenth centuries however, immersion, presumably maximising the removed by the vascular system (Michel, hydrotherapy experienced a resurgence, effects of vasodilation, and that therapy 2004; Swartz, 2001; Fu et al, 2009). At commonly ascribed to the practices of finishes on a cold cycle (Fiscus et al, 2005; the heart of Starling’s hypothesis is the Sebastian Kneipp (1821–97), a Catholic Morton, 2007). concept that it is simply the balance priest in Bavaria, who continued earlier between hydrostatic and oncotic work of Vincent Priessnitz (1799–1851), The lymphatic system: fundamental concepts pressures within the capillaries and an Austrian peasant farmer (Greek of its structure and function the interstitial space that determine Medicine, 2009). According to Michalsen The lymphatic system plays an integral fluid movement across the capillary et al (2003), ‘hydrotherapy (according to role in immune surveillance and general endothelium. While hydrostatic forces
Journal of Lymphoedema, 2011, Vol 6, No 2 73
Baker.indd 3 07/12/2011 14:50 Clinical REVIEW
are involved, meticulous studies have tethered to the interstitium by elastic due to skeletal muscle contractions, shown some of the earlier basic fibres that move in concert with the respiratory movements and arterial assumptions to be incorrect, and surrounding tissue, opening and closing pulsations playing an important but new theories regarding movement of the valve-like flaps, creating a pumping lesser role (von der Weid and Zawieja, protein and fluid into the interstitium activity that facilitates convection of 2004; Olszewski, 2008). have been proposed and substantiated the interstitial fluid and lymph uptake (Michel and Curry, 1999; Michel, 2004; (Swartz, 2001; Cueni and Detmar, 2008; Neural and hormonal modulation of Levick, 2004; Curry, 2005). Interestingly Ohtani and Ohtani, 2008). Once formed, lymphatic function: similarities between the however, they are yet to appear in most lymph is returned to the systemic vascular and lymphatic systems standard medical physiology teaching venous circulation, moving from the Many factors, hormonal, neural and texts, perhaps due to the more complex more distal lymphatic collecting vessels myogenic, have been shown to modify nature of the model and the lag in to larger lymphatic trunks and then the contractility of lymphatic collecting updating textbooks. ducts. For the majority of the body, the vessels and trunks, and hence the ability final stages of transport occur via the of the system to move lymph (McHale, Specifically, a thin glycoprotein thoracic duct, a large lymphatic vessel 1985, 1995; van Helden and Zhao, matrix lining the vascular endothelium, emptying into the central venous system 2000; Ohhashi et al, 2005; Surgery referred to as the glycocalyx or sugar at the junction of the left subclavian Online, 2009). Of particular importance coat (Weinbaum et al, 2007), plays a and internal jugular veins; for the upper to the possible effects of contrast significant role in determining vascular right side of the body, lymph returns hydrotherapy on lymphatics, are permeability. In short, the glycocalyx is a via the right thoracic duct, emptying studies showing that the contractility of major barrier to protein movement into at the junction of the right subclavian lymphatic vessels is enhanced by both the interstitium, with such movement and internal jugular veins (Swartz, 2001; direct neural stimulation and exogenous only occurring uni-directionally and Skandalakis et al, 2007; Ohtani and α-adrenergic agonists, an effect predominantly via active transcellular Ohtani, 2008; Fu et al, 2009; Jurisic and abolished by α-adrenergic antagonists. vesicular transport. In contrast, fluid Detmar, 2009; Surgery Online, 2009). Notably, ß-adrenergic agonists appear and electrolytes enter the interstitium, to cause relaxation of lymphatic vessels under the influence of hydrostatic The lymphatic system is a low with evidence that this is mediated pressure, through narrow tortuous inter- pressure system relying on both intrinsic through nitric oxide production endothelial tight junctions. In this manner, and extrinsic pumping activity to move (Browse 1968; Khaisman, 1982; Mahe et filtration occurs along the entire length lymph in a caudocranial direction, al, 1989; McHale and Roddie, 1983a, b; of the capillary, only dwindling to low often against a significant hydrostatic McHale, 1985, 1990, 1995; McGeown levels at the venule end (Michel, 1999; pressure, especially when a person is et al, 1987; Ikomi et al,1991; Sjoberg Levick, 2004; Michel, 2004; Curry, 2005; standing (Zawieja, 2009). Of particular and Steen, 1991; Dobbins, 1992; von Weinbaum et al, 2007). Importantly, importance in this transport are the der Weid and van Helden, 1996). in most tissues there is no sustained intermediate collecting vessels whose Such observations are consistent with capillary resorption of fluid, electrolytes walls are sectioned into small segments, histological and microscopic studies or proteins, with the lymphatic system termed lymphangions, by one-way (Khaisman, 1982; Ohhashi et al, 1982; being responsible for the resorption of valves that prevent retrograde flow. McHale, 1985, 1990) showing the the entire transcapillary filtrate. Only in Lymphangions are rich in smooth muscle lymphatics to be innervated by nerves the case of hypovolaemia shock is there and have intrinsic contractile activity, displaying adrenergic morphological said to be a transient net movement of being able to modify their contractility characteristics. These nerves originate fluid from the interstitial space back into and stroke volume, in response to in the nearby vasculature and extend the vascular system (Levick, 2004). changes in preload; analogous to that to the lymphatic vessels where they described by the Frank-Starling Law of enter the adventitia and penetrate as Lymph is formed by the movement the Heart (Boron and Boulpeap, 2009). deeply as the smooth muscle layer. In of protein-rich fluid from the interstitial As stated by Zawieja (2009), ‘Elevated comparison to the level of innervation space into lymphatic capillaries that are lymph pressure acting via an increase of the surrounding vasculature however, distributed throughout the interstitium. in the stretch of the lymphatic vessel is the lymphatics appear to be less These capillaries, at the most distal end a classic activator of the lymph pump. densely innervated (Alessandrini in of the lymphatic tree, are blind-ended Stretch of the lymphatics increases the McHale, 1985). tubular structures, composed of a single lymphatic contraction frequency and layer of overlapping endothelial cells initially increases the phasic contraction Studies in humans with complex that form simple, one-way valve-like strength. However, further increases in regional pain syndrome type 1 (a.k.a. flaps, enabling material to enter, but not pressure/stretch eventually produce a reflex sympathetic dystrophy) have leave. Lacking a basement membrane fall in the phasic contraction strength.’ confirmed that the peripheral lymphatics and smooth muscle, lymphatic capillaries Intrinsic pumping by lymphangions is said are under sympathetic control and have no intrinsic contractile properties. to be the primary mechanism by which that there is an intimate relationship Their cytoskeletons however are lymph moves, with extrinsic pumping between the neural vasomotor
74 Journal of Lymphoedema, 2011, Vol 6, No 2
Baker.indd 4 07/12/2011 14:51 Clinical REVIEW
control of the vasculature (also an observations, in the author’s opinion, al (2006) showing that such increases α-adrenoreceptor mediated process) it seems likely that low levels of in pressure and shear stress, lead to and that of the lymphatics (Howarth et α-adrenergic sympathetic vasomotor vessel relaxation and more efficient al, 1999; Reinauer et al, 1994; Mamiya tone to the lymphatics may enhance pumping. From these observations, et al, 2001). Specifically, overactivity flow with higher levels leading to vessel it was hypothesised (Gasheva et al, in the sympathetic nervous system dysfunction, with a reduction in flow and 2006; Zawieja, 2009) that the lymphatic in these patients was associated with perhaps even flow arrest. endothelium produces nitric oxide peripheral vasoconstriction (mediated in response to loading and increased by α-adrenoreceptors), causing the The identification of nitric oxide shear stress, relaxing the vessel wall, limbs to be pale and cool. The limbs in the 1980s as a major vasoactive enabling efficient diastolic filling and also displayed lymphoedema with agent involved in the local control more efficient pumping. It is an intrinsic reduced lymph flow, as shown by of vessel tone revolutionised our mechanism, identical to that found in lymphoscintigraphy, presumably due to understanding of the biology of the the vascular system. Moreover, at higher ineffective pumping by the lymphatics vascular endothelium (Nobel Prize, levels of filling, shear stress, and hence and perhaps subsequent flow arrest. 1998). Since then, nitric oxide has increased nitric oxide production, there Sympathectomy in these patients not been shown to be an early marker of is complete relaxation of the lymphatic only restored blood flow, colour and endothelial dysfunction in patients with smooth muscle with subsequent loss of warmth to the affected limb, due to a vascular disease (Paniagua et al, 2001; intrinsic contractility and pumping activity. reduction in α-adrenergic vasomotor Belardinelli, and Perna, 2002; Craiem This hypothesis provides a hormonally tone and subsequent vasodilation, et al, 2008). Vascular endothelial cells mediated plausible explanation of flow but also increased lymph flow, again use nitric oxide synthase (NOS) to arrest at high pressures. demonstrated by lymphoscintigraphy continually synthesise nitric oxide from (Howarth et al, 1999). That such (L)-arginine, with its synthesis increasing The studies described above increased levels of sympathetic in response to flow and shear stress highlight how both sympathetic stimulation can disrupt lymph flow within the vessel. Although it has a short vasomotor tone and flow mediated seems contrary to experiments where half-life, it acts on adjacent smooth nitric oxide production play a similar vessel contraction and lymph flow have muscle cells in the tunica media of the role in controlling vessel tone and the been shown to be stimulated by not vessel wall causing their relaxation, movement of fluid in the vascular and only sympathetic neurotransmitters, which in turn increases vessel diameter, lymphatic systems. Given this, and the targeted to α-adrenergic receptors, but reducing shear stress and increasing interdependence of lymph production also direct nerve stimulation (McHale flow. Of significance, recent studies have and flow on hydrostatic pressure in et al, 1980; McHale and Roddie, 1983a, shown that lymphatic vessels also use the vascular system, in the author’s b; McHale, 1985, 1990; McGeown et al, nitric oxide to regulate tone, contractile opinion it seems reasonable to expect 1987; Dobbins, 1992). activity and flow, with its production also that some of the beneficial effects of being upregulated by increases in shear contrast hydrotherapy on the vascular Much work has been done by stress within the vessel (Mizuno et al, system, as described below, would also McHale in elucidating the impact of 1998; Hagendoorn et al, 2004; Ohhashi, influence the lymphatic system in a the nervous system on the contractile et al 2005; Zawieja, 2005; Quick et al, positive manner. activity of the lymphatics. The answers 2009; Miteva et al, 2010). perhaps lie in observation made in early Contrast hydrotherapy gives the peripheral experiments summarised by McHale As described above, elevations in vasculature and nervous systems a work-out: (1985). In particular, at low levels of lymph pressure are a classic activator evidence from studies on athletes sympathetic nerve stimulation, and of the lymphatic pump, but only up to In sports medicine, contrast hence synaptic noradrenaline release, a point where increased pressure and hydrotherapy has been used for many contraction is coordinated and flow stretch in the system leads to a decline years to speed recovery following is induced, while at increased levels in pumping activity and flow arrest training and competition, and to of stimulation contraction becomes (Davis et al, 2009). Zawieja (2009) has improve subsequent performance. uncoordinated and the vessel spasms, shown that the flow arrest observed While initially its use was based on leading to ineffective pumping and at high flow rates, and hence shear anecdotal evidence, there is now flow arrest (McHale, 1990). Similarly, stresses, is dependent on the lymphatic a significant body of scientific data Mahe et al (1989) have shown that endothelium and its constitutive NOS supporting the practice. For example, low levels of exogenous noradrenaline, activity, as endothelial denudation and post-exercise, contrast hydrotherapy and a concomitant ß-adrenoreceptor inhibition of NOS prevent the flow has been shown to reduce the time antagonist to ensure activation of arrest. Also, Miteva et al (2010), through required to clear lactate from the α-adrenoreceptors only, increased direct measurements, demonstrated blood (Kuligowski et al, 1998; Morton, spontaneous lymphatic contractility, increases in nitric oxide production in 2007), for the heart to return to its whereas high levels of noradrenaline response to increased lymphatic vessel resting rate (Hamlin, 2007; Buchheit decreased contractility. From these flow and shear stress, with Gasheva et et al, 2009), and for general physical
Journal of Lymphoedema, 2011, Vol 6, No 2 75
Baker.indd 5 07/12/2011 14:51 Clinical REVIEW
recovery following training (Coffey muscle in the cutaneous vessels of the on the smooth muscle of peripheral et al, 2004; Ingram et al, 2009). It has skin (Boron and Boulpeap, 2009). lymphangions, essentially giving them a also been shown to reduce fatigue light work-out and stimulating lymph flow and muscle soreness post-training In the case of hydrotherapy, (see below). Moreover, the significant and to increase performance levels when thermoreceptors in the skin cyclical changes in cutaneous blood flow, in subsequent exercise (Vaile et al, sense warm water they relay this to and hence pressures within the vascular 2008). It is worth mentioning however, the central nervous system (CNS), capillary bed, should increase movement that while not all studies have shown which, in an attempt to maintain of fluid into the interstitium, as reported significant effects, as noted in a review core body temperature, reduces by Convetino (1987). This primes the by Wilcock et al (2006), those that efferent sympathetic vasomotor tone lymphatic pump, which can be further have appear to be scientifically robust. to α-adrenoreceptors in cutaneous synergistically activated by the increase in vessels. This causes relaxation of sympathetic tone. A review by Cochrane (2004) smooth muscle in the vessel wall and of contrast hydrotherapy in athletes vasodilation, lowering peripheral vascular Contrast hydrotherapy improves long-term concluded that while ‘the physiologic resistance and facilitating heat loss. blood flow and endothelial function: evidence effects of hot-cold water contrast baths The opposite is seen upon cold water from subjects with peripheral arterial disease for injury treatment have been well treatment, with such reciprocal changes Contrast hydrotherapy, and even documented… its physiological rationale in peripheral vascular resistance being thermal sauna therapy, not only improve for enhancing recovery is less known’. well documented (Bonde-Petersen et peripheral blood flow in the short term, In this regard, there is a recurring, and al, 1992). Indeed, most body heat is lost as described above, but also appear somewhat attractive if not reductionist through convection when it is carried to improve long-term blood flow and hypothesis in the literature regarding by blood to cutaneous vessels in the endothelial function by modifying the the mechanism by which contrast skin, with only a small amount being vascular endothelium. One study of hydrotherapy promotes recovery in dissipated by direct conduction through patients with significant peripheral athletes. As noted in the review by tissues to the skin (Boron and Boulpeap, arterial disease with debilitating Cochrane (2004), ‘most experimental 2009). Moreover, there is great capacity claudication demonstrated that a three- evidence suggests that hot-cold water in this system, as cutaneous vasodilation week course of contrast hydrotherapy, immersion helps to reduce injury in the through this mechanism can increase consisting of ten 25-minute sessions acute stages… through vasodilation and blood flow to the skin by up to 10-fold with alternating 45°C and 10°C vasoconstriction thereby stimulating (Boron and Boulpeap, 2009). water every three seconds, lead to a blood flow thus reducing swelling.’ prolonged (one year) and significant With more relevance to the lymphatics From these observations it is reduction in claudication, paralleled by however, Prentice (1999) has suggested important to reiterate two points. significant improvements in distal blood that ‘contrast therapy causes a cycle of Firstly, contrast hydrotherapy causes pressure and flow (Elmstahl et al, 1995). local vasoconstriction and vasodilation, marked cyclical changes in cutaneous creating a type of “pumping” action that blood flow. Secondly, such changes Similarly, subjects with either risk would enhance venous and lymphatic are due to corresponding changes factors for cardiovascular disease or removal of edema’. in the tonicity of efferent impulses in chronic cardiac failure have shown the sympathetic vasomotor system, significant improvements in endothelial- A study into the effects of contrast acting through α-adrenoreceptors dependent flow-mediated vasodilation hydrotherapy on blood flow in the legs in peripheral cutaneous vessels. In following thermal sauna therapy of athletes demonstrated a 200–300% simple terms, contrast hydrotherapy is (Imamura et al, 2001; Kihara et al, increase in arterial blood flow above giving both the peripheral vasculature 2002), with a similar study showing control levels during a four-minute (as suggested by Woodmansey et al, additional improvements in quality of warm phase, followed by a rapid drop 1938), and the vasomotor arm of the life and resting heart rate (Michalsen et in blood flow, to around 30–40% below peripheral nervous system a work-out. al, 2003). Imamura (2001) and Kihara control levels, during a subsequent one- This is of significance, as the lymphatics (2001) suggest that such dramatic minute cold phase (Fiscus et al, 2005). are also innervated by the sympathetic and long-term improvements in flow Repetition of this cycle over 20 minutes nervous system, as described above, are triggered in the first instance saw transient increases and decreases with sympathetic activity also mediated by thermally mediated vasodilation, in blood flow during respective warm through α-adrenoreceptors, stimulating increasing flow and shear stress at and cold phases. This phenomena is the lymphatic pump (Browse, 1968; the vascular endothelium, resulting in due to a fundamental homeostatic Khaisman, 1982; McGeown et al, 1987; both acute increases in endothelial mechanism essential in the regulation of McHale and Roddie, 1983a, b; McHale, nitric oxide production and more core body temperature. It is mediated 1990,1995). Hence, it is possible that long-term activation of endothelial through changes in sympathetic contrast hydrotherapy, by cyclically NOS expression. As mentioned above, efferent vasomotor tone affecting changing sympathetic tone to the nitric oxide produced by the vascular α-adrenoreceptors of vascular smooth peripheries, has a stimulating effect endothelium causes relaxation of
76 Journal of Lymphoedema, 2011, Vol 6, No 2
Baker.indd 6 07/12/2011 14:51 Clinical REVIEW
smooth muscle cells in the tunica and garments (Moseley et al, 2007). can lead to a deconditioning of skeletal media of the vessel wall. This causes While they provide short-term relief, muscles (Hayes, 2010). As hypothesised dilation of the vessels, reducing shear in some cases up to 40% reduction in by Lane et al (2005), ultimately this may stress and endothelial damage, which limb volume (Moseley et al, 2007), for lead to a gradual decline in lymphatic subsequently improves blood flow, patients with secondary lymphoedema function due to a lack of flow with nutrient delivery and vessel health. they do not provide a long-term cure. vessel atrophy. This is a well-reported phenomena, To date, there is no effective cure with flow-mediated nitric oxide for secondary lymphoedema, with It is now apparent from a body dependent vasodilation being used studies suggesting that its progressive of clinical evidence, that exercising a clinically as a sensitive marker of early nature (Hayes, 2008; Sagen et al, 2009; limb at risk, including aerobic exercise, vascular dysfunction (Paniagua et al, Rourke et al, 2010) is due to a gradual targeted resistance training or 2001; Belardinelli and Perna, 2002; decline in the contractile activity of the weight training, does not exacerbate Craiem et al, 2008). lymphatic vessels and subsequent valvular lymphoedema, and in some cases even incompetence (Witte et al, 2000). leads to a reduction in limb volume If contrast hydrotherapy were (McKenzie and Kalda, 2003; Hayes et able to stimulate lymph flow in Advice aimed at reducing the risk al, 2009; McNeely et al, 2009; Sagen the short term (Fiscus, et al 2005), of lymphoedema (Hayes, 2008; Schmitz, et al, 2009; Godoy et al, 2010; Kim and cutaneous thermal therapy 2010) suggests the avoidance of et al, 2010). In many of these studies, can markedly increase lymph flow activities that stimulate lymph flow, such patients also reported improvements (Olszewski et al, 1977), there would be as vigorous or repetitive exercise, and in general health, vitality, well-being an associated increase in shear stress extremes of temperature. Such advice and psychological health secondary and hence nitric oxide production was historically given, as lymphoedema, to the exercise regimens. Of greater (Miteva et al, 2010). Such short-term especially following treatment for breast significance perhaps are the results changes in nitric oxide production cancer, was thought to be due to a of a recent prospective randomised should lead to improved pumping reduced capacity to transport lymph controlled trial looking at the effects efficiency, as shown by Gasheva et al in the affected limb, secondary to a of exercise on the development of (2006). In turn, this may lead to more restriction in lymph outflow, caused by lymphoedema in patients who have long-term upregulation of NOS activity damage or removal of more proximal survived breast cancer (Schmitz, 2010). in the lymphatic endothelium, with lymph nodes. It is now realised that Upon randomisation into the trial, improvements in lymph flow, vessel development of lymphoedema in such none of the patients had clinical signs growth and repair. Recent studies have patients is not simply due to proximal of lymphoedema. The intervention shown that nitric oxide and endothelial obstruction (Lane et al, 2005). If this was a three-month supervised NOS play a vital role in mediating were the case, it would be expected and slowly graded weight-lifting vascular endothelial growth factor to present more immediately following programme, followed by nine months of (VEGF) dependent lymphangiogenesis treatment. Only a minority of cases unsupervised weights, with the control (Kajiya et al, 2008; Lahdenranta et al, present following treatment, with most not partaking in exercise. The end point 2009). Again, this parallels the situation cases presenting after a few months or was the incidence of lymphoedema at in the vascular system, where nitric years, being triggered by an event that one year. This was significantly reduced oxide and endothelial NOS also damages the remaining lymphatics, such in all women partaking in the exercise play a central role in VEGF-mediated as a minor infection following a cut or programme (11% vs 17%), an effect that angiogenesis (Hagendoorn, 2005). graze (Pain et al, 2005). was even more marked in those women who had five or more lymph nodes Current treatments for lymphoedema, the There is a great deal of confusion removed (7% vs 22%). Given these multifactorial aetiology of this disease and surrounding the recommendations for findings, it appears that clinical advice a possible treatment and preventative role exercise in patients with lymphoedema, to avoid excessive and repetitive use for contrast hydrotherapy or at risk of developing it. To date, some of an at-risk limb, and to avoid carrying The majority of conventional societies involved in the management heavy objects with it, was ill-founded treatments for the management of of lymphoedema still advise patients to and perhaps detrimental. However, it lymphoedema are conservative, with avoid using the affected limb for carrying is important to emphasise that when their primary aim being a reduction objects (Schmitz, 2010). As discussed by patients are instructed to exercise in the in the volume of the affected limb, Hayes (2008), such recommendations first instance following recovery from to restore function and quality of life are not founded on good quality clinical treatment, it be carefully monitored in (Horning, 2007). The more common evidence, but rather based on theory the initial stages, with gradual increments and effective treatments, based on and limited data. In the minds of patients to a point where the patient is gaining quality clinical evidence, include at risk of developing lymphoedema maximal benefit. complex physical therapy, manual however, they lead to a mind-set (Lee lymphatic drainage (MLD), limb et al, 2009), where the patient avoids The example given above regarding elevation, and compression bandages using the limb, or uses it minimally. This exercise and lymphoedema highlights
Journal of Lymphoedema, 2011, Vol 6, No 2 77
Baker.indd 7 07/12/2011 14:51 Clinical REVIEW
the fact that not all historical guidelines hydrotherapy may prove to be not only Can J Sport Sci 12(S1): 136S–139S for the prevention and management an effective treatment for lymphoedema, Craiem D, Chironi G, Simon A, Levenson of lymphoedema, founded on theory but perhaps also an effective prophylaxis. J (2008) New assessment of endothelium- and not based on clinical evidence, While this concept is theoretical, based dependent flow-mediated vasodilation to may be correct. This has relevance on the many similarities between the characterize endothelium dysfunction. Am J Ther 15(4): 340–4 to contrast hydrotherapy, as similar vascular and lymphatic systems in terms recommendations exist suggesting that of innervation and vessel biology, it is Cueni LN, Detmar M (2008) The lymphatic patients avoid exposing their at-risk given some clinical credence by the system in health and disease. Lymph Res Biol 6(3/4): 109–22 limb to extremes of temperature. For marked improvement in claudication example, Horning and Guhde (2007) in patients with peripheral vascular Curry FE (2005) Microvascular solute and advise patients to avoid: disease following contrast hydrotherapy water transport. Microcirculation 12: 17–31 8 Exposure to extreme cold, which can (Elmstahl et al, 1995). As appears to Davis MJ, Davis AM, Ku CW, Gashev AA be associated with rebound swelling, be the case with exercise however, (2009) Myogenic constriction and dilation of or chapping of skin a gradual introduction of contrast isolated lymphatic vessels. Am J Physiol Heart Circ Physiol 296: H293–H302 8 Prolonged (>15 minutes) exposure hydrotherapy with temperatures that to heat, particularly hot tubs are not too extreme may be the best Dobbins DE (1992) Catecholamine-mediated and saunas approach in initial investigations of this lymphatic constriction: involvement of both α1- and α2-adrenoreceptors. Am J Physiol 8 Immersing the limb in water hypothesis. It is an exciting new area 263(Heart Circ Physiol 32): H473–H478 temperatures above 102°F (38.8°C). that warrants clinical investigation with Elmstahl S, Lilja B, Bergqvist D, Brunkwall pilot trials. JL J (1995) Hydrotherapy of patients with Hayes (2008) also notes the advice intermittent claudication: a novel approach to ‘avoid heat, including sunburns or to improve systolic ankle pressure and tanning, hot baths and saunas’, but is References reduce symptoms. Int Angiol 14: 389–94 again careful to make the distinction Ambrose CT (2006) Immunology’s first Fine Life Wellness Spa (2009) Hydrotherapy. that, ‘evidence supporting or refuting priority dispute — an account of the 17th- Available online at: http://finelifehealth.net/ these guidelines (not all listed here) century Rudbeck-Bartholin feud. Cell treatment_hydrotherapy.htm> [last accessed is scarce’. This was also highlighted by Immunol 242: 1–8 April 2011] Rymal (2002) in a letter responding Belardinelli R, Perna GP (2002) Vasomotor Fiscus KA, Kaminski TW, Powers ME (2005) to the question, ‘Can patients at risk reactivity evaluation in cardiac rehabilitation. Changes in lower-leg blood flow during for lymphedema use hot tubs?’. Here, Monaldi Arch Chest Dis 58(2): 79–86 warm-, cold-, and contrast-water therapy. Arch Phys Med Rehabil 86: 1404–10 it was reported that only anecdotal Bonde-Petersen F, Schultz-Pedersen clinical evidence suggests that hot L, Dragsted N (1992) Peripheral and Fu MR, Ridner SH, Armer J (2009) Post- tubs can precipitate oedema, and central blood flow in man during cold, breast cancer lymphedema: Part 1. The thermoneutral, and hot water immersion. pathophysiology of lymphoedema. Am J Nurs that even the experts cannot form 109(7): 48–54 a consensus regarding this topic. To Aviat Space Environ Med 63(5): 346–50 this end, there are no studies in the Boron W, Boulpeap E (2009) Medical Gasheva OY, Zawieja DC, Gashev AA (2006) Contraction-initiated NO-dependent literature that investigate the effect of Physiology. 2nd edn. Saunders/Elsevier, Philadelphia lymphatic relaxation: a self-regulatory contrast hydrotherapy on secondary mechanism in rat thoracic duct. J Physiol lymphoedema. There are, however, two Browse NL (1968) Response of lymphatics 575(3): 821–32 studies showing that cutaneous thermal of canine hind limb to sympathetic nerve stimulation. J Physiol 197: 25–36 Godoy MFG, Oliani AH, Pereira de Godoy therapy (44°C hot water) can markedly JM (2010) Active exercises utilizing a improve lymph flow (Olszewski et Buchheit M, Peiffer JJ, Abbiss CR, Laursen facilitating device in the treatment of al, 1977) and reduce the volume PB (2009) Effect of cold water immersion on lymphedema resulting from breast cancer postexercise parasympathetic reactivation. therapy. Ger Med Sci 18(8): 1–4 of lymphoedematous legs (Liu and Am J Physiol Heart Circ Physiol 296(2): Olszewski, 1993). H421–7 Greek Medicine (2009) The Water Cure. Available online at:
78 Journal of Lymphoedema, 2011, Vol 6, No 2
Baker.indd 8 07/12/2011 14:51 Clinical REVIEW
temperature water therapy on repeated sprint cancer-related lymphedema: a randomized Circulation. Elsevier Science Publishers, performance. J Sci Med Sport 10(6): 398–402 controlled trial. Arch Phys Med Rehabil 91: London: chap 5 1844–8 Hayes SC (2008) Review of research evidence McHale NG (1990) Lymphatic innervation. on secondary lymphoedema: Incidence, Kuligowski LA, Lephart SM, Giannantonio Blood Vessels 27: 127–36 prevention, risk factors and treatment. FP, Blanc RO (1998) Effect of whirlpool McHale NG (1995) Nature of lymphatic National Breast and Ovarian Cancer Centre. therapy on the signs and symptoms of innervation. In: Reed RK, McHale NG, Bert Available online at:
Journal of Lymphoedema, 2011, Vol 6, No 2 79
Baker.indd 9 07/12/2011 14:51 Clinical REVIEW
org/nobel_prizes/medicine/laureates/1998/ risk: Exercise versus deconditioning for html [last accessed 5 December 2011] breast cancer survivors. Exerc Sport Sci Rev 38(1): 17–24 Ohhashi T, Kobayashi S, Tsukahara S, Azuma T (1982) Innervation of bovine mesenteric Schmitz KH, Ahmed RL, Troxel AB, Cheville Key points lymphatics: From the histochemical point of A, Lewis-Grant L, Smith R, et al (2010b) view. Microvasc Res 24(3): 377–85 Weight lifting for women at risk for breast 8 Contrast hydrotherapy, cancer-related lymphedema: A randomised Ohhashi T, Mizuno R, Ikomi F, Kawai Y which involves the trial. JAMA 304(24): 2699–705 (2005) Current topics of physiology and immersion or dousing of a pharmacology in the lymphatic system. Sjoberg T, Steen S (1991) Contractile limb in alternating hot and Pharmacol Ther 105: 165–88 properties of lymphatics from the human cold water, has been shown lower leg. Lymphology 24(1): 16–21 Ohtani O, Ohtani Y (2008) Organisation and to improve distal blood developmental aspects of lymphatic vessels. Skandalakis JE, Skandalakis LJ, Skandalakis flow and vessel function Arch Histol Cytol 71(1): 1–22 PN (2007) Anatomy of the lymphatics. Surg in patients with peripheral Oncol Clin N Am 16: 1–6 Olszewski W, Engeset A, Jeger PM (1977) arterial disease who suffer Flow and composition of the leg lymph in Surgery Online (2009) Anatomy and from claudication. normal men during venous stasis, muscular physiology of the lymphatic system. Available activity and local hyperthermia. Acta Physiol online at: http://surgeryonline.wordpress. Scand 99: 149–58 com/2009/02/19/anatomy-and-physiology- 8 It has been shown to cause of-the-lymphatic-system/ [last accessed 28 acute changes in blood flow Olszewski W (2008) Contractility patterns April 2010) to limbs ( flow with warm of human leg lymphatics in various stages of ↑ obstructive lymphoedema. Ann NY Acad Sci Swartz MA (2001) The physiology of the water), presumably through 1131: 110–8 lymphatic system. Adv Drug Deliv Rev 50: autonomically mediated 3–20 Pain SJ, Vowler S, Purushotham AD (2005) changes in the tone of Axillary vein abnormalities contribute to Vaile J, Halson S, Gill N, Dawson B (2008) the peripheral arterioles, development of lymphoedema after surgery Effect of hydrotherapy on recovery from secondary to the changes in for breast cancer. Br J Surg 92: 311–5 fatigue. Int J Sports Med 29(7): 539–44 the cutaneous temperature Paniagua OA, Bryant MB, Panza JA (2001) van Helden DF, Hosaka K, Imtiaz MS (2006) of the limb. Role of endothelial nitric oxide in shear Rhythmicity in the microcirculation. Clin stress-induced vasodilation of human Hemorheol Micro 34: 59–66 8 Such changes in flow microvasculature diminished activity in van Helden DF, Zhao J (2000) Lymphatic are known to increase hypertensive and hypercholesterolemic vasomotion. Clin Exp Pharmacol Physiol 27: patients. Circulation 103: 1752–8 sheer stress within vessels 1014–8 and this is proposed as Piller NB, Birrell S (2003) ‘Lymphoedema: von der Weid P-Y, van Helden DF the mechanism through how to treat.’ Australian Doctor, 6th June (1996) ß-Adrenoreceptor-mediated which increased flow Prentice WE (1999) Therapeutic modalities in hyperpolarisation in lymphatic smooth improves vessel nitric oxide sports medicine. 4th edn. WCB McGraw-Hill, muscle of guinea pig mesentry. Am J Physiol production and overall St Louis 270(Heart Circ Physiol 39): H1687–H1965 vessel health. Quick CM, Ngo BL, Venugopal AM, Stewart von der Weid PY, Zawieja DC (2004) RH (2009) Lymphatic pump-conduit duality: Lymphatic smooth muscle: the motor unit of 8 Recent evidence suggests contraction of postnodal lymphatic vessels lymph drainage. Int J Biochem Cell Biol 36: inhibits passive flow.Am J Physiol Heart Circ 1147–53 that the vascular and Physiol 296: H662–68 lymphatic systems have Water Cure (2010) Hippocrates and the Reinauer S, Goerz G, Holzle E, Heusgen WaterCure. Available online at: http:// much in common with F, Dinter W, Tarnow J, et al (1994) Distal www.watercure2.org/hippocrates.htm [last regards innervation by the edema and hyperhidrosis of the arm. accessed 25 September 2010] autonomic nervous system Symptoms of reflex sympathetic dystrophy Weinbaum S, Tarbell JM, Damiano ER (2007) and their cell biology, with (Sudeck’s disease). Hautarzt 45(10): 696–701 The structure and function of the endothelial respect to flow mediated Rourke LL, Hunt KK, Cormier JN (2010) glycocalyx layer. Annu Rev Biomed Eng 9: nitric oxide production. Breast cancer and lymphedema: a current 121–67 overview for the healthcare provider. Women’s Wilcock IM, Cronin JB, Hing WA (2006) 8 This paper discusses Health 6(3): 399–406 Water immersion: Does it enhance recovery the concept of contrast Rymal C (2002) Can patients at risk for from exercise? Int J Sports Physiol Perform hydrotherapy as a possible lymphedema use hot tubs? Clin J Oncol Nurs 1(3): 195–206 therapy for the prevention 6(6): 369 Witte CL, Witte MH, Unger EC, Williams and management of Sagen A, Karesen R, Risberg MA (2009) WH, Bernas MJ, McNeill GC et al (2000) lymphoedema. Physical activity for the affected limb and Advances in imaging of lymph flow arm lymphedema after breast cancer surgery. disorders. Radiographics 20: 1697–1719 A prospective, randomized controlled trial Woodmansey A, Collins DH, Ernst MM with two years follow-up. Acta Oncologica (1938) Vascular reactions to the contrast 48: 1102–10 bath in health and in rheumatoid arthritis. Zawieja DC (2009) Contractile physiology of Schmitz KH (2010a) Balancing lymphoedema Lancet 2: 1350–3 lymphatics. Lymphat Res Biol 7(2): 87–9
80 Journal of Lymphoedema, 2011, Vol 6, No 2
Baker.indd 10 07/12/2011 14:51