The primary findings of this study were that femoral artery diameter and peak blood flow response after cuff occlusion were reduced in the SCI compared with able-bodied individuals. However, these reductions were evident only for the absolute values, as correcting for the reduced muscle volume in SCI individuals eliminated the differences in diameter and blood flow. To our knowledge, this is the first study to investigate vascular changes in SCI individuals in relation to changes in muscle volume. This result suggests that adaptations in muscle vascular function closely parallel skeletal muscle atrophy in SCI individuals. Furthermore, we observed a prolonged blood flow recovery after cuff occlusion in SCI individuals possibly indicating altered vascular reactivity.
We found approximately a 35% reduction in lower limb muscle CSA and volume of chronic, complete SCI compared with AB subjects. It is well documented that significant muscle atrophy occurs after complete SCI due to extreme inactivity. Mean CSA of single fibers from SCI individuals is two thirds the size of able-bodied muscle (14). Muscle CSA as determined by MRI, is reduced by one third in the muscles of the lower limb (3) and in the quadriceps femoris (6) compared with age-matched control subjects. Other studies have indicated that muscle CSA decreases from 1 to 17 months after injury and is roughly 50% of able-bodied controls (24). It should be noted that our measurements of muscle volume underestimated the total leg muscle volume. This was done to conform to the sensitive volume of the magnetic resonance magnet and to make use of reproducible landmarks. The muscle volume measures should be relatively consistent between SCI and able-bodied individuals. Interestingly, by excluding the thigh muscles above the start of the gluteal muscle, we may be more accurately matching muscle mass perfusion to the femoral artery at the level where vessel diameter measurements were made.
Our results indicate that femoral artery diameter size was significantly reduced by 40% in SCI compared with able-bodied individuals. However, this difference was no longer significant when the diameter was expressed relative to muscle volume. Our finding without normalization to muscle volume is consistent with previous literature in chronic tetraplegics (16) and paraplegics (1,7,8). These results are significant as they suggest that decreases in arterial diameter size may be matched to muscle atrophy that occurs in SCI individuals.
Peak blood flow response to reactive hyperemia was significantly lower in the SCI compared with the able-bodied group. This finding is consistent with previous literature that has shown blood flow is lower in SCI compared with able-bodied individuals after 5 min of cuff occlusion (16) and with exercise (8). However, when we expressed blood flow relative to lower leg muscle volume there was no longer a significant difference in response to cuff occlusion (Fig. 4). These findings indicate muscle blood flow per unit muscle mass is not impaired in SCI individuals after reactive hyperemia.
NIRS was used as an independent measure of blood flow. A previous study has used the rate of recovery of oxygen saturation after cuff ischemia as a marker of the ability to deliver oxygen (15). With short cuff durations (up to 4–5 min), there is little or no depletion of phosphocreatine, and thus the hyperemic flow response after cuff release should reflect the inflow of oxygenated blood. The lack of difference in rate of reoxygenation between SCI and able-bodied individuals supports the hypothesis that normalized blood flow is not impaired in SCI individuals. In this study, we used 10 min of cuff ischemia, which should have resulted in some depletion of phosphocreatine (15) and thus an increase in postcuff oxygen consumption. As SCI patients have reduced mitochondrial density (2) and impaired muscle oxidative enzymes (23), we expected the recovery from the 10 min cuff to be slower in SCI than for able-bodied individuals. This was not the case, and we can only suggest that the amount of phosphocreatine depletion with 10 min of cuff ischemia (not measured) was not enough to demonstrate the expected differences in oxidative capacity.
We did not find a significant difference in resting blood flow between groups. This finding is in contrast to several studies in which a lower resting blood flow has been reported in SCI individuals (8,29). The difference between results could be due to methodological differences between studies. By normalizing our resting data by muscle mass, we actually found that resting blood flow was higher in the SCI group than the able-bodied group. It is possible that the high resting blood flows in the SCI group in our study were a result of our not obtaining a “true” resting condition. Some of our SCI subjects had muscle spasms when they were transferred to the examination table. This increase blood flow coupled with a slow rate of recovery of blood flow may have elevated our resting values. Our study design included waiting 10 min after transferring to try to account for this, but it is possible that resting blood flow was still elevated. Another possibility is that blood flow at rest may be in excess after disuse due to poor coupling between metabolic demand and blood flow (30). This would be consistent with a deconditioned vascular system or the decrease in sympathetic activity found below the level of injury in SCI subjects (9).
A prolonged halftime to recovery of blood flow was found in the SCI compared with the able-bodied group. The prolonged halftime to recovery of blood flow is in agreement with our previous results in incomplete SCI (17) and complete SCI individuals (18). Halftime to recovery of blood flow has been used previously as an index of vascular reactivity (22,25), and this would suggest that SCI individuals have reduced vascular reactivity. Activity status has been related to vascular reactivity as inactivity is associated with reduced vascular reactivity (26) and exercise training improves vascular reactivity (19). Furthermore, reduced vascular reactivity has been associated with many diseases including diabetes (27) and heart disease (4). This study was not designed to address the mechanism behind the reduced vascular reactivity. It could indicate a greater buildup of metabolic factors/vasoactive substances after cuff occlusion and/or a diminished ability to remove them. Reduced sympathetic tone may also play a role. The lack of any differences between SCI and able-bodied individuals in the pattern of desaturation during cuff ischemia or the rate of recovery after ischemia suggest that the reduced vascular reactivity is not due to differences in metabolic rate or in oxygen delivery. Regardless of the exact mechanism, the prolonged halftime to recovery would suggest that vascular reactivity is altered in the SCI subjects. Future studies could be designed to look at the exact mechanism behind this finding. Consequences of reduced vascular reactivity are abnormal oxidative metabolism, increased insulin insensitivity, or hypertension (31); all of which are prevalent in SCI individuals (12).
Lastly, our results indicate that a maximal blood flow response is not elicited with 4 min of cuff occlusion, as there was a significant increase in peak blood flow from 4 to 10 min of cuff occlusion. Furthermore, the groups were similar in their responses to both 4 and 10 min of cuff occlusion. This finding is contrary to others that suggest using different cuff durations to obtain maximal flow for various populations (5). Our results suggest that similar cuff durations should be used when comparing between able-bodied and SCI subjects and that at least a 10-min cuff is needed to elicit a maximal response. Previous results in our laboratory have indicated that flow after 10 min of cuff occlusion has been sufficient to elicit a maximal response in able-bodied subjects (Olive, J. L., unpublished observations, July 2001).
In conclusion, this study found that lower-limb muscle volume, femoral artery diameter size, and blood flow were significantly reduced in complete, chronic SCI individuals compared with able-bodied individuals. The significant reductions in femoral artery size and blood flow in SCI individuals were no longer different when expressed per unit muscle volume. This study is one of the first studies that have demonstrated that vascular remodeling and muscular atrophy are closely linked. Furthermore, we found a significant prolonged recovery of blood flow to baseline after cuff occlusion, which may suggest reduced vascular reactivity in complete SCI subjects. Future studies need to investigate the mechanisms and the time course for vascular remodeling and muscle atrophy to determine whether they are dependent upon each other.
The authors would like to acknowledge Ron Meyer, Ph.D., for his assistance in magnetic resonance image analysis by use of X-Vessel, and Scott Bickel and Jill Slade for their assistance with subject recruitment. We would also like to thank Chris Black, Vanessa Castellano, Lee Stoner, Allison DeVan, Chris Elder, Kristen Dudley, and Michelle Layton for their assistance in data collection.
Financial support was provided by the Paralyzed Veterans Association and NIH grants HL65179 and HD39676.
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