1727
J Physiol 592.8 (2014) pp 1727–1728
T R A N S L AT I O N A L P E R S P E C T I V E S
Increasing venous return as a strategy to prevent or reverse cardiac dysfunction following spinal cord injury Heidi L. Lujan and Stephen E. DiCarlo Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
The Journal of Physiology
Email: [email protected] ‘Spinal cord injury is a ferocious assault on the body that leaves havoc in its wake. Paralysis is certainly part of its legacy, but there are other equally devastating consequences including autonomic dysfunction, compromised cardiovascular, bowel, bladder, and sexual function. Treatments and cures for these losses would greatly improve the quality of life for all of us living with spinal cord injury’ (Christopher Reeve, September 30, 2004; Reeve, 2005). In fact, when surveyed, individuals living with spinal cord injury (SCI) state that their quality of life is severely impacted by the consequences of impaired cardiovascular function (Anderson, 2004). However, cardiovascular dysfunction following SCI remains an under-investigated area compared with motor and sensory dysfunction (Inskip et al. 2009). Nevertheless, understanding the mechanisms responsible for the cardiovascular dysfunction as well as therapeutic strategies for improving cardiovascular function, has the potential to impact the lives of millions of individuals and families living with SCI (Anderson, 2004). In this issue of The Journal of Physiology, West and colleagues (West et al. 2014), in a series of well-designed studies, have addressed the mechanisms responsible for cardiovascular dysfunction, as well as provided a therapeutic strategy to prevent or reverse the dysfunction for individuals with SCI. Using a combination of techniques and lines of evidence, the investigators demonstrated that SCI is associated with a rapid (as early as 1 week post injury) and sustained impairment in cardiac structure and function. Specifically, following SCI there was an altered Starling curve and significant myocardial fibrosis. The myocardial fibrosis was associated with an up-regulation of a well-known fibrotic signalling pathway.
Remarkably, passive lower-limb cycling prevented the SCI-induced impairments in cardiac structure and function, prevented myocardial fibrosis, and improved blood lipid profiles. The data suggest that passive lower-limb cycling represents a new strategy for reducing the cardiovascular dysfunction associated with SCI. The cardiac dysfunction associated with SCI may be a response to chronic pressure and volume unloading. The chronic pressure and volume unloading may be a result of the rapid and sustained reduction in both mean arterial pressure and end-diastolic volume, secondary to the loss of sympathetic vasoconstrictor tone below the level of the injury (Fig. 1). Furthermore, passive cycling may exert a cardio-protective effect via an increased venous return and a subsequent volume loading of the heart, which in turn maintains contractile function while pre-
venting fibrosis (Fig. 1). In this context, other interventions that increase venous return (e.g. abdominal binding, West et al. 2012; external leg compression, Helmi et al. 2013) may become additional strategies to improve cardiac function for individuals with SCI, inactivity or venous pooling. Accordingly, the results have important implications for understanding the mechanisms responsible for the high mortality rates and incidence of cardiovascular disease in individuals with SCI as well as suggesting an important therapeutic strategy. Specifically, increasing venous return and arterial pressure may improve or prevent cardiac dysfunction following SCI. This strategy may also be effective for a number of other physiological and environmental conditions (inactivity/bed rest/spaceflight, neurological diseases, myocardial infarction) that result in similar impairments in cardiac structure and function.
Figure 1. Strategy to Prevent Cardiac Dysfunction Following SCI Spinal cord injury results in: (1) loss of sympathetic vasoconstrictor tone below the level of the injury, which (2) reduces arterial pressure, end-diastolic pressure and causes venous pooling; together, this causes chronic pressure and volume unloading (3), unloaded arterial baro-receptors with resultant reduced cardiac parasympathetic activity and enhanced cardiac sympathetic activity (4), all of which cause cardiac dysfunction and structural remodelling (5). Passive exercise (6), by increasing venous return, arterial pressure and volume loading (7–8) loads arterial baro-receptors, enhances cardiac parasympathetic activity and reduces cardiac sympathetic activity (9). As a result, cardiac dysfunction and structural remodelling are prevented or reversed (10).
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
DOI: 10.1113/jphysiol.2014.272666
1728 As a result, this original and innovative research has the potential to have a major impact on the field, because, before this study, it was believed that passive exercise has little to no impact on cardiovascular function. The new data challenge this belief and help to advance our knowledge of the potential clinical utility of passive exercise. However, the study does not definitively identify the mechanism by which passive exercise improves cardiac dysfunction. While increasing venous return may be important, additional mechanisms are also probably operative. Future studies are required to evaluate the underlying mechanisms in experimental preparations,
Translational Perspectives and, clinically, it will be important to determine whether passive exercise can reduce cardiovascular dysfunction in individuals with underlying pathologies that predispose them to prolonged inactivity or venous pooling.
References Anderson KD (2004). J Neurotrauma 21, 1371–1383. Helmi M, Lima A, Gommers D, van Bommel J & Bakker J (2013). Future Cardiol 9, 645–648. Inskip JA, Ramer LM, Ramer MS & Krassioukov AV (2009). Spinal Cord 47, 2–35.
J Physiol 592.8
Reeve C (2005). Dedication. In Progress in Brain Research, Autonomic Dysfunction after Spinal Cord Injury, ed. Weaver L & Polosa C, p. ix. Elsevier Science, The Netherlands. West CR, Campbell IG, Shave RE & Romer LM (2012). Respir Physiol Neurobiol 180, 275–282. West CR, Crawford MA, Poormasjedi-Meibod M-S, Currie KD, Fallavollita A, Yuen V, McNeill JH & Krassioukov AV (2014). J Physiol 592, 1771–1883.
Additional information Competing interests
None declared.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
J Physiol 592.8 (2014) pp 1727–1728
T R A N S L AT I O N A L P E R S P E C T I V E S
Increasing venous return as a strategy to prevent or reverse cardiac dysfunction following spinal cord injury Heidi L. Lujan and Stephen E. DiCarlo Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
The Journal of Physiology
Email: [email protected] ‘Spinal cord injury is a ferocious assault on the body that leaves havoc in its wake. Paralysis is certainly part of its legacy, but there are other equally devastating consequences including autonomic dysfunction, compromised cardiovascular, bowel, bladder, and sexual function. Treatments and cures for these losses would greatly improve the quality of life for all of us living with spinal cord injury’ (Christopher Reeve, September 30, 2004; Reeve, 2005). In fact, when surveyed, individuals living with spinal cord injury (SCI) state that their quality of life is severely impacted by the consequences of impaired cardiovascular function (Anderson, 2004). However, cardiovascular dysfunction following SCI remains an under-investigated area compared with motor and sensory dysfunction (Inskip et al. 2009). Nevertheless, understanding the mechanisms responsible for the cardiovascular dysfunction as well as therapeutic strategies for improving cardiovascular function, has the potential to impact the lives of millions of individuals and families living with SCI (Anderson, 2004). In this issue of The Journal of Physiology, West and colleagues (West et al. 2014), in a series of well-designed studies, have addressed the mechanisms responsible for cardiovascular dysfunction, as well as provided a therapeutic strategy to prevent or reverse the dysfunction for individuals with SCI. Using a combination of techniques and lines of evidence, the investigators demonstrated that SCI is associated with a rapid (as early as 1 week post injury) and sustained impairment in cardiac structure and function. Specifically, following SCI there was an altered Starling curve and significant myocardial fibrosis. The myocardial fibrosis was associated with an up-regulation of a well-known fibrotic signalling pathway.
Remarkably, passive lower-limb cycling prevented the SCI-induced impairments in cardiac structure and function, prevented myocardial fibrosis, and improved blood lipid profiles. The data suggest that passive lower-limb cycling represents a new strategy for reducing the cardiovascular dysfunction associated with SCI. The cardiac dysfunction associated with SCI may be a response to chronic pressure and volume unloading. The chronic pressure and volume unloading may be a result of the rapid and sustained reduction in both mean arterial pressure and end-diastolic volume, secondary to the loss of sympathetic vasoconstrictor tone below the level of the injury (Fig. 1). Furthermore, passive cycling may exert a cardio-protective effect via an increased venous return and a subsequent volume loading of the heart, which in turn maintains contractile function while pre-
venting fibrosis (Fig. 1). In this context, other interventions that increase venous return (e.g. abdominal binding, West et al. 2012; external leg compression, Helmi et al. 2013) may become additional strategies to improve cardiac function for individuals with SCI, inactivity or venous pooling. Accordingly, the results have important implications for understanding the mechanisms responsible for the high mortality rates and incidence of cardiovascular disease in individuals with SCI as well as suggesting an important therapeutic strategy. Specifically, increasing venous return and arterial pressure may improve or prevent cardiac dysfunction following SCI. This strategy may also be effective for a number of other physiological and environmental conditions (inactivity/bed rest/spaceflight, neurological diseases, myocardial infarction) that result in similar impairments in cardiac structure and function.
Figure 1. Strategy to Prevent Cardiac Dysfunction Following SCI Spinal cord injury results in: (1) loss of sympathetic vasoconstrictor tone below the level of the injury, which (2) reduces arterial pressure, end-diastolic pressure and causes venous pooling; together, this causes chronic pressure and volume unloading (3), unloaded arterial baro-receptors with resultant reduced cardiac parasympathetic activity and enhanced cardiac sympathetic activity (4), all of which cause cardiac dysfunction and structural remodelling (5). Passive exercise (6), by increasing venous return, arterial pressure and volume loading (7–8) loads arterial baro-receptors, enhances cardiac parasympathetic activity and reduces cardiac sympathetic activity (9). As a result, cardiac dysfunction and structural remodelling are prevented or reversed (10).
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
DOI: 10.1113/jphysiol.2014.272666
1728 As a result, this original and innovative research has the potential to have a major impact on the field, because, before this study, it was believed that passive exercise has little to no impact on cardiovascular function. The new data challenge this belief and help to advance our knowledge of the potential clinical utility of passive exercise. However, the study does not definitively identify the mechanism by which passive exercise improves cardiac dysfunction. While increasing venous return may be important, additional mechanisms are also probably operative. Future studies are required to evaluate the underlying mechanisms in experimental preparations,
Translational Perspectives and, clinically, it will be important to determine whether passive exercise can reduce cardiovascular dysfunction in individuals with underlying pathologies that predispose them to prolonged inactivity or venous pooling.
References Anderson KD (2004). J Neurotrauma 21, 1371–1383. Helmi M, Lima A, Gommers D, van Bommel J & Bakker J (2013). Future Cardiol 9, 645–648. Inskip JA, Ramer LM, Ramer MS & Krassioukov AV (2009). Spinal Cord 47, 2–35.
J Physiol 592.8
Reeve C (2005). Dedication. In Progress in Brain Research, Autonomic Dysfunction after Spinal Cord Injury, ed. Weaver L & Polosa C, p. ix. Elsevier Science, The Netherlands. West CR, Campbell IG, Shave RE & Romer LM (2012). Respir Physiol Neurobiol 180, 275–282. West CR, Crawford MA, Poormasjedi-Meibod M-S, Currie KD, Fallavollita A, Yuen V, McNeill JH & Krassioukov AV (2014). J Physiol 592, 1771–1883.
Additional information Competing interests
None declared.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
