Preserved Cardiac Function After Chronic Spinal Cord Injury

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ORIGINAL ARTICLE

Preserved Cardiac Function After Chronic Spinal Cord Injury Patricia C. de Groot, PhD, Arie van Dijk, MD, PhD, Erika Dijk, MSc, Maria T. Hopman, MD, PhD ABSTRACT. de Groot PC, van Dijk A, Dijk E, Hopman MT. Preserved cardiac function after chronic spinal cord injury. Arch Phys Med Rehabil 2006;87:1195-200. Objective: To assess the effect of chronic deconditioning on cardiac dimensions and function in subjects with high-level spinal cord injury (SCI), who represent a human in-vivo model of extreme inactivity. Design: Cross-sectional study. Setting: University medical center. Participants: Seven men with tetraplegia and 7 able-bodied controls. Interventions: Not applicable. Main Outcome Measures: Echocardiographic measurements of resting cardiac dimensions, systolic function, and global and long-axis diastolic function. Results: Left ventricular mass index was significantly lower in the subjects with SCI than in the controls (90.8⫾26g/m2 vs 122⫾28.9g/m2; P⫽.05). In addition, dimensions of left ventricle, left atrium, and vena cava inferior were all significantly reduced in the subjects with SCI compared with controls (P⬍.05). There were no differences between the groups for any of the parameters reflecting systolic and global and long-axis diastolic function. Conclusions: Tetraplegia is associated with a reduction in cardiac mass and dimensions. Resting diastolic and systolic function is not altered with continued exposure to inactivity, however, which suggests a remodeling of the heart as a physiologic adaptive process. Key Words: Atrophy; Cardiovascular deconditioning; Echocardiography; Rehabilitation. © 2006 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation HANGES IN PHYSICAL ACTIVITY lead to marked changes in cardiac structure, ranging from the “physioC logic hypertrophy” of the endurance-trained athlete, to the 1

“physiologic atrophy” of chronically deconditioned patients. For example, decreases in cardiac volumes, dimensions, and/or left ventricular (LV) mass in humans have been observed after a period of bedrest (2–12wk),2,3 after space flight by astronauts,4 and after spinal cord injury (SCI).5-8 Similar changes in LV dimensions9 and cardiac mass9,10 were seen in adult rats after simulated microgravity by hindlimb unloading.

From the Departments of Physiology (de Groot, Dijk, Hopman) and Cardiology (van Dijk), Radboud University Medical Centre Nijmegen, The Netherlands. Supported by the Dutch Organization for Health Research and Development. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Correspondence to Maria T. Hopman, MD, PhD, Dept of Physiology, Radboud University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands, e-mail: [email protected]. Reprints are not available from the author. 0003-9993/06/8709-10735$32.00/0 doi:10.1016/j.apmr.2006.05.023

SCI results in sublesional motor dysfunction, which is more substantial in patients with cervical SCI.11 Consequently, these people have a wheelchair-bound, inactive lifestyle, which is illustrated by maximal oxygen uptake values averaging approximately 0.7L/min12 or 12mL·kg–1·min–1.13 Hence, the most extreme degree of inactivity possible is experienced by tetraplegic subjects who are otherwise healthy. Previous studies using echocardiography found a significant reduction in cardiac dimensions and mass in subjects with tetraplegia.5-8 Although changes in cardiac dimensions with different modes of inactivity seem to be well described, the effect of inactivity on cardiac function has rarely been investigated. Impairment of diastolic function has been recognized as an important component of heart failure and changes in diastolic filling associated with physical inactivity may be a specific risk factor in the development of heart failure.14,15 Only a few studies have reported that cardiac output was reduced after periods of inactivity induced by bedrest or SCI,7,16 whereas the effect of inactivity on diastolic function remains obscure. Levine et al3 found a reduction in LV distensibility and impaired cardiac function due to reduced filling after 2 weeks of bedrest,3 whereas Eysmann et al8 reported no changes in diastolic filling in a group of subjects with SCI who were compared with age-matched controls. Our main objective in this study was to assess the effect of chronic deconditioning on cardiac dimensions and function in a group of subjects with cervical SCI, who serve as a natural model for extreme inactivity. We hypothesized that tetraplegia is associated with reductions in both cardiac dimension and function, as compared with able-bodied persons. In addition to more traditional measurements for cardiac dimension and function, we used innovative echocardiography techniques to measure diastolic and systolic function. METHODS Participants Seven men with SCI who were between the ages of 28 and 48 years, and 7 able-bodied male controls who were between the ages of 27 and 48 years, volunteered to participate in the study. The SCI subjects had motor complete neurologically stable spinal cord lesions of traumatic origin at levels C5-6 (American Spinal Injury Association grade A)11; time since injury varied between 4 and 30 years (mean, 17.7⫾9.6y). Inclusion criteria for both groups included age less than 50 years, with no known coronary artery, cardiac, or pulmonary disease or other chronic medical problems—including cancer, diabetes, and hypertension—that required regular medical therapy. Five subjects with SCI used medication to suppress spasms, while 2 also used medicine for their bowel function. At the time of the study, the control subjects were low to moderately active, with their activity ranging from routine daily activities to walking and/or cycling 2 to 3 hours a week. All participants with SCI used electric wheelchairs for locomotion. The ethics committee of the Radboud University Medical Centre Nijmegen approved the study and all subjects provided written, informed consent before participating. Arch Phys Med Rehabil Vol 87, September 2006

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Protocol All measurements were performed in a quiet, temperaturecontrolled room (range, 22°–24°C) at the Department of Cardiology of the Radboud University Hospital Nijmegen. Blood pressure was measured manually at the brachial artery with a sphygmomanometer.a Body mass in SCI was measured using a specialized sitting scale,b while body mass of controls and height in both groups were taken from a medical questionnaire. Echocardiographic measurements, using standard views and formulas as recommended by the American Society of Echocardiography,17-19 were obtained by a single cardiologist using the Vingmed System Five.c Echocardiography using the 2-dimensional, M-mode, Doppler of mitral inflow and pulmonary venous velocities, and tissue Doppler imaging modalities of both the septum and lateral wall at the mitral annulus were performed with the subjects placed in the left lateral position. Images were obtained in multiple cross-sectional planes using second harmonic imaging with a phased-array transducer (range, 1.7–3.5MHz) in standard positions. An electrocardiographic signal was recorded simultaneously with the echo images. Raw data were stored digitally for off-line analysis using EchoPAC PC.c In all measurements, 3 beats were averaged, with the subject pausing during the respiratory cycle at end expiration. Clear, 2-dimensional, echocardiographic images were obtained from all subjects. Cardiac dimensions and cardiac output were corrected for body surface area using the formula of Dubois and Dubois.20 Measurements: Dimensions From the M-mode echocardiogram, we measured the diameter of the aorta, left atrium, left ventricle at end-diastole (LVED) and at end-systole (LVES), end-diastolic wall thickness of the intraventricular septum (IVS), and left ventricular posterior wall (LVPW) in the parasternal long-axis view. From the 2-dimensional echocardiogram, we measured length and width from the left atrium, and diameter of the vena cava inferior at end expiration in the apical 4-chamber and subcostal view, respectively. LV mass was calculated using a geometric cube formula21: (1.04⫻[(LVED⫹LVPW⫹IVS)3⫺LVED3]⫻ 0.8⫹0.6)/1000. We used the ratio of LVED mass/volume to evaluate the degree of adaptation of wall thickness to changes in chamber size. Measurements: Function Systolic function. We measured the ejection fraction using the formula: (LVEDV–LVESV/LVEDV)⫻100, where left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) from 2-dimensional echocardiograms in the apical 4-chamber view were determined using the single-plane Simpson rule method.22 Cardiac output was calculated by Doppler-derived stroke volume by heart rate. Therefore, stroke volume was measured using the formula: ¼⫻␲⫻(LVOTdiameter)2⫻LVOTVTI, where LVOT is left ventricular outflow tract and VTI is velocity time integral. A measure of systolic performance corrected for afterload was calculated as the peak systolic pressure/end systolic volume (PSP/ESV) ratio. Diastolic function. Parameters reflecting global diastolic function were measured with the echo-Doppler technique and color M-mode. To measure filling velocities, we obtained standard LV inflow pulsed-wave Doppler measurements at the mitral leaflet tips, including peak flow velocity of the early rapid filling wave (E[-wave]), peak flow velocity of the late filling wave due to atrial contraction (A[-wave]), the E/A ratio, (early deceleration time), and isovolumetric relaxation time. In Arch Phys Med Rehabil Vol 87, September 2006

addition, left atrium inflow pulsed-wave Doppler measurements were obtained, including pulmonary venous flow velocities in both diastole (D) and systole (S), and the S/D ratio. To quantify diastolic suction, color M-mode measurements at the center of the mitral inflow region were obtained, including early diastolic flow propagation velocity (vp). Parameters reflecting long-axis diastolic function were measured with the tissue Doppler imaging (TDI) technique. To measure myocardial relaxation, we obtained pulsed-wave TDI measurements at the septal and lateral mitral annulus, including early LV systolic myocardial tissue contraction velocity (Sm[-wave]), peak early LV diastolic myocardial tissue filling velocity (Em[-wave]), and peak late LV diastolic myocardial tissue filling velocity during atrial contraction (Am[-wave]). Statistical Analysis Statistical analyses were performed using the Statistical Package for Social Sciences.d All data are expressed as mean ⫾ standard deviation (SD). Differences in physical and echocardiographic measurements between the 2 groups were analyzed using an unpaired Student t test. Two-tailed significance levels were used throughout. For all statistics, a P value of .05 or less was considered statistically significant. RESULTS Baseline Characteristics Both groups were well matched for age, sex, height, body mass, and body surface area. Subjects with SCI had significantly lower values of systolic and diastolic blood pressure than with the controls. Heart rate and stroke volume did not differ between the groups (table 1). Echocardiography: Dimensions Because body surface area values did not differ between groups, data corrected for body surface area, with the exception of LV mass, was not considered, and only absolute values are presented (table 2). LV dimensions were significantly smaller in the subjects with SCI compared with the controls, which is indicated by a 12% reduction in LVED and a 14% reduction in LVES. LV mass index was significantly reduced (26%) in SCI subjects compared with controls. In addition, left atrium size (21%) and the diameter of the vena cava inferior (28%) were significantly smaller in the SCI subjects. No differences between groups were observed for aorta diameter, IVS, LVPW, LVEDV, and LVESV, although a trend toward a decrease in

Table 1: Subject Characteristics Characteristics

SCI (n⫽7)

Controls (n⫽7)

P

Age (y) Height (cm) Weight (kg) BSA (m2) SBP (mmHg) DBP (mmHg) Heart rate (bpm) Stroke volume (mL)

38⫾8 180⫾6 72⫾14 1.9⫾0.2 97⫾10 61⫾4 53⫾8 73⫾20

37⫾8 178⫾7 72⫾7 1.9⫾0.1 125⫾6 79⫾10 58⫾10 88⫾34

.83 .90 .66 .93 ⬍.01* ⬍.01* .32 .34

NOTE. Values are mean ⫾ SD. Abbreviations: BSA, body surface area; DBP, diastolic blood pressure; SBP, systolic blood pressure. *Significantly different, subjects with SCI versus controls.

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CARDIAC FUNCTION AFTER LONG-TERM INACTIVITY, de Groot Table 2: Cardiac Dimensions

Table 4: Global Diastolic Function

Dimensions

SCI (n⫽7)

Controls (n⫽7)

P

Measures

SCI (n⫽7)

Controls (n⫽7)

P

Aorta diameter (mm) Left atrium (mm) LVED (mm) LVES (mm) IVS (mm) LVPW (mm) Left atrium length (mm) Left atrium width (mm) VCI (mm) LV mass index (g/m2) LVEDV (mL) LVESV (mL) M/V ratio

31.0⫾4.1 32.8⫾5.7 48.1⫾3.6 30.1⫾1.5 7.2⫾1.1 7.5⫾1.3 48.4⫾6.7 31.0⫾7.3 16.0⫾4.2 90.8⫾26.0 87.0⫾15.5 37.8⫾7.9 1.06⫾0.27

26.1⫾1.6 41.5⫾7.7 54.6⫾4.4 34.9⫾2.7 7.9⫾1.0 7.4⫾1.0 52.3⫾8.9 41.1⫾6.7 22.3⫾2.1 122.2⫾28.9 107.1⫾24.5 42.0⫾12.4 1.16⫾0.23

.12 .03* .01* ⬍.001* .29 .89 .38 .02* .01* .05* .10 .47 .48

E (cm/s) A (cm/s) E/A Dt (ms) IVRT (ms) S (cm/s) D (cm/s) S/D vp (cm/s) E/vp

80⫾11 48⫾14 1.8⫾0.5 193⫾36 94⫾21 50⫾7 62⫾12 0.8⫾0.2 61⫾16 1.4⫾0.3

81⫾13 48⫾14 1.8⫾0.4 181⫾23 83⫾33 52⫾7 55⫾10 1.0⫾0.3 57⫾13 1.5⫾0.6

.81 .95 .94 .46 .46 .56 .24 .31 .60 .55

NOTE. Values are mean ⫾ SD. Abbreviations: M/V ratio, LV mass/LVEDV; VCI, diameter of the vena cava inferior at end expiration. *Significantly different, subjects with SCI versus controls.

the SCI group was evident for LVEDV. Also, the mass/volume ratio did not differ between the groups (see table 2). Echocardiography: Function Systolic function. Both ejection fraction and cardiac output did not reach statistical significance between groups, although there was a trend toward a decrease in cardiac output in subjects with SCI. In addition, no differences between the groups were observed in the afterload corrected systolic performance PSP/ESV ratio (table 3). Diastolic function. No significant differences between the groups were observed for any of parameters reflecting diastolic function (tables 4, 5). DISCUSSION In this study, we assessed the morphologic and functional adaptations of the heart after years of extreme inactivity in subjects with a complete cervical SCI (C5-6). LV mass index and cardiac dimensions of the LV and left atrium were significantly lower in subjects with SCI than in the controls. The major finding of this study, however, is that there were no significant differences between the 2 groups with respect to any of the parameters reflecting resting diastolic and systolic function. Our results show that resting cardiac function measured by echocardiography is not altered after long-term inactivity. Dimensions We found that cardiac dimensions and mass are lower in subjects with SCI than in controls, which is in agreement with previous findings.5-8 Tetraplegia is defined as a disruption of the structural and functional integrity of the cervical spinal cord

Table 3: Systolic Function Measures

SCI (n⫽7)

Controls (n⫽7)

P

CO (L/min) EF (%) PSP/ESV ratio

3.71⫾0.78 55.4⫾11.9 2.65⫾0.67

4.7⫾0.98 60.7⫾4.1 3.15⫾0.67

.06 .30 .20

NOTE. Values are mean ⫾ SD. Abbreviations: CO, cardiac output; EF, ejection fraction; PSP/ESV, peak systolic pressure/end systolic volume.

NOTE. Values are mean ⫾ SD. Abbreviations: A, late transmitral filling velocity due to atrial contraction; D, pulmonary venous flow velocity in diastole; Dt, deceleration time of early transmitral filling velocity; E, early transmitral filling velocity; IVRT, isovolumic relaxation time; S, pulmonary venous flow velocity in systole; vp, early diastolic flow propagation velocity.

that results in muscle paralyses below the level of the lesion and loss of supraspinal autonomic control. As a consequence of extensive physical deconditioning and muscle atrophy, the oxygen demand of the body’s muscles is low and the cardiac load is diminished. Oxygen delivery is thus adjusted accordingly, which leads (most likely via flow-dependent mechanisms) to vascular atrophy and to a lower total blood volume in tetraplegia.23,24 Both vascular atrophy and a reduced total blood volume further reduces cardiac filling, stroke volume, and cardiac output.25 As a result of the sympathetic dysfunction in SCI, systemic blood pressures may be altered, thus influencing cardiac dimensions as well.26 In the periphery, vasoregulation and muscle pump activity in areas below the spinal cord lesion are absent, thereby disturbing the redistribution of blood and, hence, attenuating cardiac preload; this causes a reduction in mean systemic filling pressure and LVEDV.5,7,27 People with tetraplegia also lack cardiac sympathetic innervation manifested by a lower heart rate and additional impairment of cardiac performance.12,13 As a consequence of the adaptive mechanisms described above, LV wall stress may decrease, which could result in the “adaptive” cardiac atrophy.4,5

Table 5: Long-Axis Diastolic Function Measures

SCI (n⫽6)

Controls (n⫽7)

P

Sm’s (cm/s) Em’s (cm/s) Am’s (cm/s) Sm’l (cm/s) Em’l (cm/s) Am’l (cm/s) Em (cm/s) E/Em

7⫾2 11⫾3 7⫾2 8⫾3 14⫾7 7⫾2 12⫾5 6.8⫾2.0

8⫾1 13⫾1 9⫾2 7⫾2 16⫾3 8⫾2 15⫾2 5.6⫾0.7

.42 .12 .16 .68 .52 .30 .35 .22

NOTE. Values are mean pulsed-wave tissue Doppler imaging measurements at the septal and lateral mitral annulus ⫾ SD. Abbreviations: Am’l, late diastolic myocardial filling velocity from the lateral wall; Am’s, late diastolic myocardial filling velocity from the septal wall; E, early transmitral filling velocity; Em, early LV diastolic myocardial tissue filling velocity; Em’l, early diastolic myocardial tissue filling velocity from the lateral wall; Em’s, early diastolic myocardial tissue filling velocity from the septal wall; Sm’l, early systolic myocardial tissue emptying velocity from the lateral wall; Sm’s, early systolic myocardial tissue emptying velocity from the septal wall.

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The importance of calcium in the control of cardiac function is well established, but its role as a key second messenger in signal transduction pathways that control the growth of the heart has only recently been recognized.28 Previous studies have suggested an important role of sympathetic mediated pathways, particularly the calcium-dependent protein phosphate calcineurin, in regulating the homeostatic size of the heart in response to loadassociated alterations in calcium handling.29 In this study, we considered SCI to be an example of extreme and long-term inactivity. We chose subjects with tetraplegia (time since injury, 4 –30y), because these patients represent the lowest extreme on a spectrum of activity. Sustained bedrest deconditioning and space flight (or simulated microgravity) are alternative models of inactivity and could also be seen as models of chronic cardiac unloading. Although SCI is accompanied by sympathetic dysfunction that influences peripheral and central circulatory regulation, there is ample evidence that the effects of bedrest3,4 and microgravity4 on LV dimensions and mass are in line with the cardiac effects seen after SCI. Figure 1 illustrates the wide range in LV mass across the total spectrum of activity, from the subjects with SCI to the endurance-trained athlete.

% Baseline (normalized to body surface area)

Function Diastolic function. One of the most important clinical consequences of cardiac atrophy may be related to diastolic, as opposed to systolic, function.4 Impaired diastolic function is recognized as an important component of heart failure,14,15 which is characterized by impaired LV function.30 Hence, changes in diastolic filling associated with longstanding inactivity may be a specific risk factor in heart failure. Previous studies2,4 have indicated that inactivity induced by bedrest and space flight is associated with impaired compliance. A recent study of elite athletes with ventricular hypertrophy reported that after a period of “relative inactivity following their off season,” the rate of ventricular relaxation during early diastole (as measured with color M-mode Doppler flow propagation velocity, a measure that is relatively insensitive to changes in preload) may be slowed.31 The authors state, however, that it is unlikely that the impaired flow propagation velocity in these “inactive” athletes is indicative of diastolic dysfunction. We show in this study that measures of flow propagation velocity did not differ between the chronically inactive subjects with tetraplegia and the able-bodied controls. Normally, global diastolic function expressed as LV filling measured by transmitral pulsed-wave Doppler shows a pattern

140

Athletes + 3 months' training

130

Athletes

120 110 Base

100 6 weeks bedrest

90 80

of filling velocities, with a prominent E-wave representing early filling during myocardial relaxation and a less prominent A-wave representing atrial systole.32 In our study, we expected that the extreme and long-term inactivity in SCI would be associated with diastolic dysfunction. Normal E/A velocity patterns were observed in subjects with SCI as well as in controls, however. To make a complete distinction between normal and abnormal LV filling velocity patterns, we quantified mitral inflow velocities with TDI. In contrast to traditional Doppler imaging of the blood pool, TDI detects the velocity of the myocardium during systole and diastole,33 thereby revealing longitudinal (ie, septal and lateral wall at the mitral annulus) diastolic function. When the TDI technique was applied, no differences were observed between groups and the results of our study clearly indicate that there is no evidence for any grade of global or local diastolic dysfunction in SCI. Systolic function. Systolic performance is a key determinant of diastolic function, particularly the early relaxation that depends in part on systolic contraction to engage the restoring forces that lead to diastolic suction. Systolic function in turn is affected by diastolic function and LV filling via the FrankStarling curve mechanism. Thus, a comprehensive examination of diastolic function would be incomplete without careful attention to systolic function as well. In this study, systolic function expressed as ejection fraction or cardiac output was not significantly altered in subjects with SCI, compared with controls, although there was a trend toward a decrease in cardiac output in the SCI subjects. Previous studies that assessed cardiac output in inactivity models reported inconsistent results. Some studies described a decrease in cardiac output after periods of inactivity by bedrest16 or SCI,7 while other studies involving space flight crew members,34 or subjects with SCI6 did not report any changes in cardiac output. In agreement with our findings, previous studies that measured ejection fraction after bedrest,35 space flight,36 or SCI6,37 did not report any changes. Because afterload may be different between the groups, we also determined the PSP/ESV ratio, which is a measure of afterload corrected systolic performance. The PSP/ESV ratio did not differ between the groups, however. Hence, despite our extensive measurements regarding diastolic and systolic function, our results reject the second part of our hypothesis that tetraplegia is associated with decrements in resting cardiac function, compared with able-bodied subjects. This raises the question: “How is it possible that cardiac function is preserved with altered cardiac dimensions after such long periods of extreme inactivity?” Theoretically, alterations in dimension could result in some cardiac remodeling as a normal physiologic adaptive response of the myocardium, in which LV dimensions decrease to maintain wall stress.4 Such adaptations may represent an appropriate response to inactivity without compromising “normal” cardiovascular function.

12 weeks bedrest

SCI

70

Fig 1. LV mass (normalized to body surface area, in g/m2) as a percentage of baseline or control across the total spectrum of physical activity from extreme deconditioning (SCI, present study), bedrest4 to the endurance-trained athletes.31

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Study Limitations We consider the SCI population as a unique “human model of nature” with which to assess central adaptations to extreme inactivity. As valuable as information gleaned from this patient population is, one should be cautious in extrapolating these results to the general population because of other unique pathologies underlying SCI, such as disturbed sympathetic innervation. Evidence that inactivity may be the main cause of the cardiac adaptations in SCI, however, comes from studies that demonstrated that most of the adaptations are reversible by functional electric stimulation (FES) training of the paralyzed muscles. Central adaptations to FES training in SCI include increases in LV mass,5 increases in LV dimensions such as LVED,6 IVS, LVPW,5 and increases in stroke volume and cardiac output.6,38

CARDIAC FUNCTION AFTER LONG-TERM INACTIVITY, de Groot

In this study, we assessed cardiac function only in subjects resting in a supine condition. It is of interest, however, whether cardiac function after long-term deconditioning is also preserved under conditions of stress such as exercise, lower body negative pressure, or orthostatic stress. Future studies of this issue are recommended. CONCLUSIONS Our results confirm our hypothesis that extreme, long-term inactivity, as experienced in tetraplegia, is associated with decrements in cardiac mass and dimension. Resting diastolic and systolic function, however, is not altered by continued exposure to inactivity. A decreased overall heart size may represent an appropriate physiologic response to inactivity without compromising “normal” cardiovascular function. Acknowledgment: This study is part of the research program “Physical Strain, Work Capacity and Mechanisms of Restoration of Mobility in the Rehabilitation of Individuals With Spinal Cord Injury.” References 1. Pluim BM, Zwinderman AH, van der Laarse A, van der Wall EE. The athlete’s heart. A meta-analysis of cardiac structure and function. Circulation 2000;101:336-44. 2. Perhonen MA, Zuckerman JH, Levine BD. Deterioration of left ventricular chamber performance after bed rest: “cardiovascular deconditioning” or hypovolemia? Circulation 2001;103:1851-7. 3. Levine BD, Zuckerman JH, Pawelczyk JA. Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation 1997;96:517-25. 4. Perhonen MA, Franco F, Lane LD, et al. Cardiac atrophy after bed rest and spaceflight. J Appl Physiol 2001;91:645-53. 5. Nash MS, Bilsker S, Marcillo AE, et al. Reversal of adaptive left ventricular atrophy following electrically-stimulated exercise training in human tetraplegics. Paraplegia 1991;29:590-9. 6. Huonker M, Schmid A, Sorichter S, Schmidt-Trucksab A, Mrosek P, Keul J. Cardiovascular differences between sedentary and wheelchair-trained subjects with paraplegia. Med Sci Sports Exerc 1998;30:609-13. 7. Kessler KM, Pina I, Green B, et al. Cardiovascular findings in quadriplegic and paraplegic patients and in normal subjects. Am J Cardiol 1986;58:525-30. 8. Eysmann SB, Douglas PS, Katz SE, Sarkarati M, Wei JY. Left ventricular mass and diastolic filling patterns in quadriplegia and implications for effects of normal aging on the heart. Am J Cardiol 1995;75:201-3. 9. Bao JX, Zhang LF, Shang HH, Yu ZB, Qian YQ. [Echocardiographic assessment of left ventricular structure and function after simulated weightlessness in rats] [Chinese]. Space Med Med Eng (Beijing) 1999;12:88-91. 10. Goldstein MA, Edwards RJ, Schroeter JP. Cardiac morphology after conditions of microgravity during COSMOS 2044. J Appl Physiol 1992;73:94S-100S. 11. Maynard FM Jr, Bracken MB, Creasey G, et al. International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord 1997;35:266-74. 12. Hooker SP, Figoni SF, Glaser RM, Rodgers MM, Ezenwa BN, Faghri PD. Physiologic responses to prolonged electrically stimulated leg-cycle exercise in the spinal cord injured. Arch Phys Med Rehabil 1990;71:863-9. 13. Van Loan MD, McCluer S, Loftin JM, Boileau RA. Comparison of physiological responses to maximal arm exercise among able-bodied, paraplegics and quadriplegics. Paraplegia 1987;25:397-405.

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Arch Phys Med Rehabil Vol 87, September 2006

38. Phillips CA, Danopulos D, Kezdi P, Hendershot D. Muscular, respiratory and cardiovascular responses of quadriplegic persons to an F. E. S. bicycle ergometer conditioning program. Int J Rehabil Res 1989;12:147-57. Suppliers a. Erkameter 300; ERKA, Kallmeyer Medizintechnik GmbH & Co, Im Farchet 15, D-83646 Bad Toelz, Germany. b. N.V. Mach: Jaffa van het Louis Smulders and Co, Utrecht, The Netherlands. c. GE Vingmed Ultrasound AS, Strandpromenaden 45, PB 141, 3191 Horten, Norway. d. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.