Jennifer L. Olive, Jill M. Slade, Gary A. Dudley and Kevin K.

McCully
J Appl Physiol 94:701-708, 2003. First published Oct 11, 2002; doi:10.1152/japplphysiol.00736.2002 You might find this additional information useful... This article cites 63 articles, 34 of which you can access free at: http://jap.physiology.org/cgi/content/full/94/2/701#BIBL This article has been cited by 4 other HighWire hosted articles: Fatigue properties of human thenar motor units paralysed by chronic spinal cord injury C. S. Klein, C. K. Hager-Ross and C. K. Thomas J. Physiol., May 15, 2006; 573 (1): 161-171. [Abstract] [Full Text] [PDF] Passive Leg Movements and Passive Cycling Do Not Alter Arterial Leg Blood Flow in Subjects With Spinal Cord Injury W. Ter Woerds, P. C. De Groot, D. H. van Kuppevelt and M. T. Hopman Physical Therapy, May 1, 2006; 86 (5): 636-645. [Abstract] [Full Text] [PDF] Muscle metabolism with blood flow restriction in chronic fatigue syndrome K. K. McCully, S. Smith, S. Rajaei, J. S. Leigh Jr. and B. H. Natelson J Appl Physiol, March 1, 2004; 96 (3): 871-878. [Abstract] [Full Text] [PDF] Increasing blood flow before exercise in spinal cord-injured individuals does not alter muscle fatigue J. L. Olive, J. M. Slade, C. S. Bickel, G. A. Dudley and K. K. McCully J Appl Physiol, February 1, 2004; 96 (2): 477-482. [Abstract] [Full Text] [PDF] Updated information and services including high-resolution figures, can be found at: http://jap.physiology.org/cgi/content/full/94/2/701 Additional material and information about Journal of Applied Physiology can be found at: http://www.the-aps.org/publications/jappl

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J Appl Physiol 94: 701708, 2003. First published October 11, 2002; 10.1152/japplphysiol.00736.2002.

Blood ow and muscle fatigue in SCI individuals during electrical stimulation

JENNIFER L. OLIVE,1 JILL M. SLADE,1 GARY A. DUDLEY,1,2 AND KEVIN K. MCCULLY1 1 Department of Exercise Science, University of Georgia, Athens 30602; and 2Shepherd Center, Atlanta, Georgia 30309
Submitted 9 August 2002; accepted in nal form 26 September 2002

Olive, Jennifer L., Jill M. Slade, Gary A. Dudley, and Kevin K. McCully. Blood ow and muscle fatigue in SCI individuals during electrical stimulation. J Appl Physiol 94: 701708, 2003. First published October 11, 2002; 10.1152/ japplphysiol.00736.2002.Our purpose was to measure blood ow and muscle fatigue in chronic, complete, spinal cord-injured (SCI) and able-bodied (AB) individuals during electrical stimulation. Electrical stimulation of the quadriceps muscles was used to elicit similar activated muscle mass. Blood ow was measured in the femoral artery by Doppler ultrasound. Muscle fatigue was signicantly greater (three- to eightfold, P 0.001) in the SCI vs. the AB individuals. The magnitude of blood ow was not signicantly different between groups. A prolonged half-time to peak blood ow at the beginning of exercise (vefold, P 0.001) and recovery of blood ow at the end of exercise (threefold, P 0.009) was found in the SCI vs. the AB group. In conclusion, the magnitude of the muscle blood ow to electrical stimulation was not associated with increased muscle fatigue in SCI individuals. However, the prolonged time to peak blood ow may be an explanation for increased fatigue in SCI individuals. spinal cord injury; Doppler ultrasound

SPINAL CORD-INJURED (SCI) individuals are at high risk of heart disease, diabetes, and obesity due to extreme inactivity inherent with their condition (35). Physical activity has been reported to decrease the risk of heart disease by 50% in sedentary, healthy individuals, as well as decrease obesity and the risk of developing diabetes and increase bone strength (1). Thus current research has been interested in the use of exercise training via electrical stimulation in SCI individuals to lower their risk of disease. However, numerous problems exist with exercise training of SCI individuals, such as increased muscle fatigue (10, 20, 24), muscle (11) and vascular (Refs. 29, 38; J. L. Olive, G. A. Dudley, and K. K. McCully, unpublished observations) atrophy, as well as reduced cardiac output (15). Muscle fatigue during volitional exercise can be dened as the failure to maintain force output that leads to a reduction in performance (19). Muscle fatigue can be explained by numerous mechanisms, which may include alterations in the neural system, muscle blood

ow and availability of metabolites to the muscle, or muscle mechanical properties (18). The increased fatigability of affected skeletal muscle is associated with an increase in fast-fatigable bers after injury due to extreme inactivity (11, 22, 59). Furthermore, impaired blood ow (17) and altered blood ow redistribution to affected muscles during exercise have been reported in SCI subjects and may contribute to increased muscle fatigue (15, 28). Limitations to maximal exercise performance in SCI individuals have been related to peripheral or muscle limitations and not to heart or lung limitations (27). Other possibilities for increased fatigue may include inadequate delivery of substrates (25, 47) or the buildup of metabolic by-products (3, 14). Submaximal exercise elicits increases in blood ow to match the metabolic demands of the working skeletal muscle (5, 65, 66, 68), regardless of muscle size (52), contraction rate (41), or type of stimulation (34), in able-bodied (AB) individuals. During submaximal exercise, blood ow will increase rapidly until oxygen delivery matches demand (49, 65) and then plateau. The initial, rapid increase in blood ow at the onset of exercise is dependent on the muscle mechanical factors (rst contraction) (62, 63) followed by vasodilation due to motor unit recruitment (rst 5 s) (34, 45, 55, 66) or vasodilators such as adenosine, nitric oxide, or potassium ions (16, 31, 45). SCI individuals have been shown to have signicant vascular changes that include reductions in blood ow and arterial diameter size by as much as 50% to affected areas (7, 29, 38, 61). This reduction in diameter size is linked to muscle atrophy in SCI individuals (Olive et al., unpublished observations). SCI individuals have also been shown to have impaired vascular reactivity (inability to regulate vascular tone) (42) as measured by half time to recovery of blood ow (Olive et al., unpublished observations; Ref. 40). Thus it is not known whether alterations in the vasculature of SCI individuals impair muscle function. Therefore, the purpose of this experiment was to measure muscle blood ow and muscle fatigue in SCI individuals during exercise via electrical stimulation. Doppler ultrasound was used in this study, a method
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that allows for the determination of absolute blood ow as well as blood ow kinetics (44, 45). Blood ow was measured during and after three different duty cycles of electrical stimulation while fatigue levels were measured. We hypothesized that the magnitude of blood ow would be lower in SCI individuals, which could contribute to their increased muscle fatigue. A second hypothesis was that SCI individuals would have a delayed recovery to exercise via electrical stimulation compared with the AB individuals.
METHODS

Subjects Nine male chronic (1 yr postinjury), complete (American Spinal Injury Association, category A) SCI subjects (8 paraplegics, 1 tetraplegic) and eight male AB subjects volunteered to participate in the study. The physical characteristics of the SCI subjects can be found in Table 1. All of the subjects in this study were part of another study (Olive et al., unpublished observations). The AB subjects, who served as controls, were included if they were similar to the SCI group in age, height, and weight and if they did not report exercising 3 days/wk and were not engaged in any formal exercisetraining program for 6 mo before the study. Exercise history in the AB subjects was obtained by self-report. Subjects were excluded if they reported that they were smokers. None of the subjects had any history of disease or other confounding factors. Medications were recorded, and the only medication that was used in either group was antispasticity medication in the SCI group. Magnetic resonance (MR) image collection for all subjects occurred at Shepherd Center, Atlanta, GA, or Health South, Athens, GA. The study was conducted with the approval of the Institutional Review Board at the University of Georgia, and all subjects provide written, informed consent. Protocol Subjects were asked to abstain from fatty foods, caffeine, and alcohol for at least 12 h before testing. This was done to eliminate the potential for diet to confound the results (43). Blood pressure (BP) was measured in the arm throughout the entire testing period by using an automated BP machine (Datascope, Mahwah, NJ). Electrical stimulation. Subjects were asked to sit on a specially made chair with a rigid lever arm positioned 70

Table 1. Individual characteristics of SCI individuals and mean data for AB and SCI groups
Subjects Age, yr Body Mass, kg Height, cm Time Since Injury, yr Level of Injury

A B C D E F G H I SCI AB

36 20 26 38 32 39 33 37 31 32.4 6.2 31.8 7.6

72.7 69.3 63.6 67.3 65.9 75.0 109.1 113.6 68.2 78.3 19.1 80.4 11.7

178 191 173 170 170 173 178 191 180 178.1 7.9 179.4 8.3

20 4 3.5 10 13 21 8 7 8 10.5 6.4

T8 T4 T7 T8 T9 T9 T10 T2 T4 T5 C5

Values are means SD for spinal cord-injured (SCI) and ablebodied (AB) groups. J Appl Physiol VOL

below horizontal. A moment arm of 33 cm was established by mounting a load cell perpendicular to and 12 in. from the axis of rotation of the lever arm. The dynamometer was calibrated by hanging known weights on the load cell. The leg was secured to the rigid level arm with an inelastic strap. Surface electrical stimulation of the right quadriceps femoris muscle was conducted by using a commercially available stimulator (TheraTouch model 4.7, Rich-Mar, Inola, OK). Isometric force was recorded on a computer with the use of MacLab 4E (Castle Hill, Australia). Surface electrodes (Uni-Patch, Wabasha, MN) were placed on the quadriceps femoris muscle: one 2 3 cm above the superior aspect of the patella, and the other lateral to and 30 cm above the patella over the vastus lateralis muscle. Subjects then received electrical stimulation inducing isometric knee extension (30-Hz train of 450-s biphasic pulse, 50-s phase delay) at a current that would elicit 30 N m of torque. This was done to elicit similar muscle activation between subjects (2, 24). Subjects underwent three different electrical stimulation bouts with a workto-rest cycle of 1:6 (Low), 1:4 (Moderate), and 1:2 (High). These levels were chosen to obtain comparable levels of fatigue among groups while allowing adequate time between contractions for blood ow measurements by Doppler ultrasound. The electrical stimulation periods lasted 3 min each. The recovery period between exercise bouts was determined by a minimum of 5 min or as the time at which blood ow returned to baseline values, whichever was shorter. The AB group did return to resting blood ow within the 5-min recovery period, whereas, in the SCI group, the time to return of baseline blood was 4 10 min. The Low bout was always performed rst and the High bout last to minimize the amount of fatigue in the subjects and to ensure that they could complete all exercise bouts. Muscle fatigue was calculated for each exercise bout as a percent decline in force production from the rst ve contractions to the last ve contractions. Blood ow. Blood ow was measured in the femoral artery by using quantitative Doppler ultrasound (General Electric LogiQ 400CL). A linear array transducer was used at a frequency of 6 9 MHz. The imaging site was located immediately distal to the femoral bifurcation and was marked to ensure replication of probe placement. Resting ow and diameter (during diastole) measurements were made before any exercise. Pulsed Doppler ultrasound was recorded in the longitudinal view by using an insonation angle between 45 and 60. The velocity gate was set to include the entire arterial diameter. Velocity measurements were autocalculated every heartbeat by GEs advanced vascular program software for the GE LogiQ 400 CL. The minimum, maximum, and time-averaged maximum velocity measurements were saved directly to a computer, thus allowing data acquisition on a beat-by-beat basis. Images were saved to magnetic optical disks for measurement of vessel diameter by custom-made software (Labview 6i, Austin, TX). Blood ow was calculated as the product of femoral artery cross-sectional area (CSA) and the timeaverage maximum velocity. The time-average maximum velocity was used in this study, despite the fact that it overestimates the mean blood ow response (40%), as it was considered a more reliable measure of the blood ow response. The resting vessel diameter was used for calculation of blood ow, as no dilation was found in the femoral artery during exercise. The observation that the femoral artery does not dilate with exercise has been reported previously (44) and has been veried in our laboratory with exercise (unpublished observations) and cuff occlusion (40). Conductance was calculated by the blood ow divided by the mean arterial
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pressure. Half time to peak blood ow was determined as the time at which blood ow increased from one-half the difference of ow at the onset of exercise to maximal ow during exercise. The time for blood ow to increase is related to the muscle pump, vasodilators, and metabolic demand during exercise (45, 63). The half time to recovery was determined as the time at which blood ow dropped to one-half the magnitudes between maximum ow and resting ow. This was used as an index of vascular reactivity, as it indicates the ability of the arteries to return blood ow to resting values (42). MR imaging. All MR images to calculate muscle volume were used in a previous study (Olive et al., unpublished observations). Skeletal muscle average CSA was determined by using proton-weighted MR imaging. This method has been shown to be highly reproducible and reliable for determination of skeletal muscle composition (37). MR images of both legs and thighs were collected with a 1.5-T magnet (500-ms repetition time, 14-ms echo time, 40-cm eld of view, 1 number of excitations, 256 256 matrix; General Electric, Milwaukee, Wisconsin). Transaxial images, 1 cm thick and 0.5 cm apart, were taken from the hip joint to the knee joint (thigh) by using a whole body coil. Each of the subjects feet was strapped to a brace to maintain the ankle joint at 90 and the knee and hip joint extended. Data were downloaded to a disk and analyzed on specically designed software (X-Vessel, East Lansing, MI). The methodology for MR image data analyses has been reported previously (33). In brief, images were automatically segmented into fat (high-intensity), muscle (midintensity), and background and bone (low-intensity) regions as follows. A preliminary segmentation of each two-dimensional slice into fat and nonfat regions was obtained by simplex optimization of the correlation between a Sobel-gradient image computed from the original image vs. the corresponding gradient images computed from single-threshold, fat-segmented images (21). This rst-pass segmentation was used to correct for intensity variations across the original image caused by radio-frequency heterogeneity (13). The corrected original image was then resegmented into the three intensity components by using a fuzzy c-mean clustering algorithm (58). Manual selection of any pixel of muscle subsequently highlighted all muscle pixels in the region and provided a total number of muscle pixels exclusive of any fat or low pixels. A manual tracing was drawn around the outside edge of the quadriceps muscles to determine quadriceps muscle mass to allow for determination of active muscle mass. For each subject, thigh CSA was determined with the rst slice not containing gluteal muscle and continuing distally toward the knee until the patella could be seen. The individual collecting the data performed two trials on sample images to determine test-retest reliability (r 0.99). Pixel number was converted to area by multiplying by the eld of view and dividing by the total number of pixels in the entire image. Statistical Analysis Independent sample t-tests (SPSS version 10.0) were conducted to compare for differences in subject characteristics and blood vessel diameter between the two groups. The data were analyzed to verify normality and to test for any outliers. Levenes test was conducted to determine equality of variances and was corrected for if inequality was found. If multiple t-tests were conducted, they were corrected by the Bonferroni method. A mixed-model, repeated-measures analysis was used to determine differences between the AB and SCI groups across exercise bouts for blood ow, conductance,
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half time to peak ow, or half time to recovery. Mauchlys test was conducted to determine whether sphericity was violated. If sphericity was violated, the repeated-measures ANOVA was corrected by using the Greenhouse-Geiser correction factor and the value for epsilon () was reported. Effect size was calculated using Cohens d (d) or eta2 (2). Missing data for half time to recovery or half time to peak blood ow were replaced by using a regression model (51). All analyses were conducted at a signicance level of 0.05.
RESULTS

Baseline Data The AB and the SCI groups were similar in age, height, and weight (Table 1). There were no signicant differences between the SCI and AB groups at rest in heart rate (HR) or BP (BP: 126/76 vs. 124/78 Torr; HR: 71 vs. 75 beats/min for AB vs. SCI). The tetraplegic subject was not a statistical outlier on any parameter and thus was included in the analyses. The SCI individuals had signicantly smaller (40%) quadriceps muscle CSA [t(15) 5.560, P 0.001, d 2.7] and volume [t(15) 5.094, P 0.001, d 2.5] than the AB group (Fig. 1). Total thigh muscle CSA [t(15) 4.264, P 0.001, d 2.1] and volume [t(15) 4.250, P 0.001, d 2.1] were signicantly smaller (40%) in the SCI compared with the AB group as well. Absolute resting blood ow (ml/min) was not different between groups (180 120 vs. 179 93 ml/min for AB vs. SCI). Muscle Fatigue There was a signicant group-by-exercise bout interaction for muscle fatigue [F(2,30) 23.028, P 0.001, 2 0.606]. Thus independent sample t-tests were conducted to determine differences between groups. The SCI group had three to eight times the amount of fatigue compared with the AB group during each exercise bout [t(15) 4.070, P 0.001, d 2.0; t(15) 4.628, P 0.001, d 2.3; and t(15) 7.863, P 0.001, d 3.9 for Low, Moderate, and High, respectively]. Repeated-measures ANOVAs were conducted to determine differences in fatigue across workloads for each group. Fatigue increased signicantly with increasing workload in the AB [F(2,14) 67.464, P 0.001, 2

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Fig. 1. Largest quadriceps muscle cross-sectional area (CSA) and total quadriceps muscle volume in spinal cord-injured (SCI) and able-bodied (AB) individuals. Values are means SD. * Signicant difference between groups, P 0.001. www.jap.org

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Fig. 2. Muscle fatigue in SCI and AB individuals. Values are means SD. * Signicant difference between groups within condition, P 0.001. # Signicant difference across exercise bouts, P 0.001.

0.906] and the SCI [F(2,16) 105.501, P 0.001, 2 0.930] groups at all exercise levels (P 0.001), except for the Low-to Moderate workload for the SCI individuals (P 0.087) (Fig. 2). Exercise Hyperemia All subjects were able to complete all three stimulation periods. There were no signicant differences in HR or BP between the groups or during the stimulation periods. A representative blood ow response to a Low workload is shown for a SCI and an AB individual (Fig. 3). Blood ow increased signicantly during each exercise bout from resting ow values [t(12) 7.299, P 0.001, d 2.5; t(12) 6.823, P 0.001, d 2.5; and t(12) 6.790, P 0.001, d 2.5 for Low, Moderate, and High, respectively] and was maximal at the end of the exercise bout. The peak blood ow at the end of exercise increased with increasing intensity of exercise [F(2,30) 19.118, P 0.001, 2 0.560] (Fig. 4). There was no difference in blood ow between groups (P 0.352). Conductance was signicantly different within exercise periods [F(2,30) 17.805, P 0.001,

Fig. 4. Peak blood ow at the end of the exercise bout. Flow values are not normalized to muscle mass; similar amounts of muscle mass were activated between individuals by altering the current of the electrical stimulation as described in METHODS. Values are means SD. # Signicant difference across exercise bouts, P 0.001. Notice that there is no difference in peak blood ow between groups.

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2 0.543], with no difference between groups. The conductance followed the trends of blood ow, as would be expected, because there were no changes in mean arterial pressure throughout exercise. As demonstrated in Fig. 3, the magnitude of blood ow was similar between groups, but the half time to peak and recovery of blood ow was signicantly prolonged (18 vs. 54 s, 8 vs. 42 s, and 8 vs. 38 s for the AB vs. SCI group at Low, Moderate, and High, respectively) in the SCI individual. The SCI individual illustrated in Fig. 3 has a prolonged half time to peak ow compared with the average response, but the gure is illustrative of the type of responses that were seen in each population. The onset and recovery of blood ow were prolonged across all exercise bouts in the SCI compared with AB groups, as measured by half time to peak blood ow [F(1,14) 15.508, P 0.001, 2 0.526] (Figs. 3 and 5) and half time to recovery [F(1,15) 52.905, P 0.001, 2 0.779] (Figs. 3 and 6). The half time to recovery was approximately three

Fig. 3. Representative example of the blood ow response before, during, and after exercise for a low workload for a SCI and AB individual. Electrical stimulation occurred between 180 and 0 s.

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Fig. 5. Half time to peak blood ow in SCI and AB individuals. Values are means SD. * Signicant difference between groups, P 0.001.

times longer in the SCI compared with the AB group. Half time to recovery of resting blood ow was longer with increasing intensities of exercise for both groups [F(1.450,21.743) 6.857, P 0.009, 2 0.314, 0.725], with signicant differences occurring between the Moderate- and High-exercise bouts (P 0.001).
DISCUSSION

We found that the magnitude of blood ow response was similar between SCI and AB individuals at three exercise bouts, even though the SCI group had significantly more muscle fatigue than the AB group. This result suggests that the magnitude of blood ow is not limiting during electrical stimulation of the quadriceps muscles and did not explain the increased fatigue seen in SCI individuals. Second, SCI individuals had prolonged blood ow kinetics at the onset of exercise and during recovery from exercise, which may be evidence of abnormal oxidative ability and impaired vascular reactivity. A unique aspect of this study was that we activated similar amounts of muscle mass (16 cm2) in both groups, allowing comparison of blood ows during exercise between SCI and AB individuals. To do this, we stimulated all subjects to the same absolute torque (30 N m), as isometric torque has been highly correlated to stimulated CSA as determined by transverse relaxation time MR imaging for SCI and AB individuals (unpublished laboratory observations) (2, 24). Calculation of activated muscle indicated that we activated 24% of AB and 42% of the SCI individuals quadriceps muscle mass. It is possible that activating different proportions of muscle mass may inuence blood ow response to electrical stimulation. This is a potential limitation to the study and is a consequence of attempting to compare subjects who have different muscle sizes. An alternative approach would have been to activate the same proportion of muscle mass and normalize ow values to the amount of activated muscle mass. Comparing subjects in this manner, however, requires determination of activated muscle mass and presents difculties with scaling (4, 60).
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We found a three- to eightfold increase in the rate of muscle fatigue in the SCI compared with the AB group at three work-rest cycles, a nding consistent with previous literature (10, 20, 24). This increase in fatigue after SCI has been associated with changes in myosin heavy chain structure from slow-oxidative to fast-glycolytic bers (22, 50, 59), decreased mitochondrial content (8,36), and alterations in the vasculature or impairments in blood ow (15, 17, 27, 28). We found no difference in the magnitude of the blood ow response at the end of exercise via electrical stimulation, demonstrating that absolute levels of muscle blood ow for a given amount of activated muscle mass are the same between groups with extremely different muscle mass and fatigue rates. Our results indicate that absolute muscle blood ow is not limiting in SCI individuals and does not explain the increased fatigue rates. Alterations in systemic pressure or HR may inuence leg blood ow during electrical stimulation in paraplegic subjects (15). However, we did not nd any changes in BP or HR during the stimulation bouts for either group, suggesting that systemic alterations did not occur and did not inuence leg blood ow during the exercise bouts. The lack of changes in BP or HR during the stimulation is most likely due to the relatively small amount of muscle activation in this study. Blood ow increased signicantly with increases in work level in both groups, a nding that is consistent with previous work in which muscle blood ow increases in proportion to the intensity of the exercise bout (5, 65, 66, 68). These ndings have been shown, regardless of muscle size (52), contraction rate (41), or type of stimulation (34). The time for blood ow to increase was signicantly prolonged (approximately equal to vefold) in the SCI group (Figs. 3 and 5). The time for blood ow to increase is dependent on muscle mechanical factors, vasodilator ability, and oxidative capacity (45, 62, 63, 65). A prolonged time to peak ow could indicate that one

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Fig. 6. Half time to recovery of blood ow in SCI and AB individuals. Values are means SD. * Signicant difference between groups, P 0.001. # Signicant difference between the moderate- and high-exercise bouts, P 0.001. www.jap.org

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or more of these mechanisms are impaired in SCI individuals. The prolonged rise in blood ow could be explained by decreased muscle pump activity, which has been reported in SCI subjects (64). A second explanation could be that blood ow response is slowed due to decreased oxidative capacity (31, 44), as is seen by reduced oxidative enzyme capacity and alterations of muscle ber type from slow-oxidative bers to fastfatigable bers in SCI individuals (8, 36). Last, the prolonged rise in blood ow could be due to impaired vessel reactivity, evidenced either as reduced vessel response to vasodilators or a reduction in the amount of vasodilators produced. Impaired vessel reactivity is prevalent in diseased populations (9, 12, 56). Furthermore, our laboratory has demonstrated that the reactive hyperemic response is impaired in SCI subjects, indicating reduced vascular reactivity (Olive et al., unpublished observations; Ref. 40). A delayed or reduced blood ow response at the onset of exercise alters oxidative metabolism in healthy individuals (23, 26, 30) and results in increased muscle fatigue in healthy working skeletal muscle (25, 48). Limited blood ow during exercise may also result in increased levels of fatigue due to an accumulation of metabolic by-products (3, 14). If ow is limited at the onset of stimulation in SCI patients, it could limit oxidative metabolism and could be one cause of the increased muscle fatigue, even though absolute muscle blood ow was not limiting. Half time to recovery of blood ow after electrical stimulation was also prolonged (approximately equal to threefold) in the SCI individuals (Figs. 3 and 6). Half time to recovery has been used as an index of vascular reactivity, as the blood ow response after exercise is dependent on the accumulation of metabolic factors and vasoactive substances such as nitric oxide and adenosine (6, 46, 53). Thus a longer half time to recovery after exercise would indicate a greater buildup of metabolic factors and/or vasoactive substances, altered sympathetic activity, and/or a diminished ability to remove them. The prolonged time to recovery is consistent with our previous results in both incomplete (40) and complete SCI individuals (Olive et al., unpublished observations) after cuff occlusion. Activity level has been shown to affect vascular reactivity. Exercise training was found to improve vascular reactivity (42), and inactivity decreased vascular reactivity as evidenced by decreased vasoconstrictor ability (54) and increased vascular resistance after a stressor (32). Furthermore, abnormal vascular reactivity has been associated with many diseases, including diabetes (57) and heart disease (12). Consequences of reduced vascular reactivity could be abnormal oxidative metabolism, increased insulin insensitivity, and/or hypertension (67), all of which are prevalent in SCI individuals (35, 36). A limitation to this study is that the SCI subjects may not have reached peak blood ow by the end of the electrical stimulation bout, as suggested in Fig. 3. In a few of the SCI subjects at the Low level, the increase in blood ow was slow enough that an obvious plateau
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was not reached during the stimulation. A longer stimulation period may have ensured that a plateau in blood ow would be reached during stimulation. However, we did not choose to use longer stimulation periods to minimize the impact of performing repeated trials. The lack of a plateau for the stimulation duration means that we may have underestimated the peak blood ow values in our SCI group. We do not think that the underestimation of peak blood ow would have changed our results signicantly for the following reasons. First, the blood ow during stimulation did not plateau in only a few SCI subjects and thus would have only a small effect on the mean peak ow. Second, the slight underestimation of peak blood ow in the SCI group would have made the nonsignicant difference between groups even smaller. Another limitation to this type of study is that blood ow measurements via Doppler ultrasound are difcult to obtain during electrical stimulation. The difculty in obtaining blood ow, especially at the High workload, made it impossible to calculate the half time to peak blood ow in some subjects, hence the use of a linear regression model to replace a few missing data points for the half time to peak blood ows. Thus conrmation of the onset kinetics needs to be conducted in future studies. In conclusion, this study has shown that the magnitude of muscle blood ow during exercise via electrical stimulation was similar between groups and does not explain the increased muscle fatigue in SCI individuals. However, the prolonged rise in blood ow at the onset of stimulation may be one explanation for increased fatigue, even though absolute muscle blood ow was not limiting. Last, we found evidence that SCI individuals have decreased vascular reactivity, which may have negative health consequences.
The authors acknowledge Dr. Ron Meyer for assistance in MR image analysis by use of X-Vessel and Scott Bickel for assistance with subject recruitment. We also thank Chris Black, Vanessa Castellano, Lee Stoner, Allison DeVan, Scott Bickel, Chris Elder, Kristen Dudley, and Michelle Layton for assistance in data collection. Financial support was provided by the Paralyzed Veterans Association and National Institutes of Health Grants HL-65179 and HD-39676. REFERENCES 1. ACSM. ACSMs Guidelines for Exercise Testing and Prescription. Philadelphia, PA: Lippincott Williams & Wilkins, 2000. 2. Adams GR, Harris RT, Woodard D, and Dudley GA. Mapping of electrical muscle stimulation using MRI. J Appl Physiol 74: 532 537, 1993. 3. Allen DG, Kabbara AA, and Westerblad H. Muscle fatigue: the role of intracellular calcium stores. Can J Appl Physiol 27: 83 96, 2002. 4. Allison D, Paultre G, Goran M, Poehlman E, and Heymseld S. Statistical considerations regarding the use of ratios to adjust data. Int J Obes Relat Metab Disord 19: 644 652, 1995. 5. Andersen P and Saltin B. Maximal perfusion of skeletal muscle in man. J Physiol 366: 233 249, 1985. 6. Bangsbo J and Hellsten Y. Muscle blood ow and oxygen uptake in recovery from exercise. Acta Physiol Scand 162: 305 314, 1998. 7. Boot CRL, Groothuis JT, van Langen H, and Hopman MTE. Shear stress levels in paralyzed legs of spinal cord-injured individuals with and without nerve degeneration. J Appl Physiol 92: 2335 2340, 2002. www.jap.org

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