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Blast-induced traumatic brain injury (bTBI) can have devastating behavioral consequences. This study was designed to evaluate the behavioral consequences of single or repeated bTBI, as evaluated by an open field (OF) test conducted in near-darkness to avoid confounding effects of illumination and photophobia. Sprague-Dawley rats under isoflurane anesthesia were exposed to a series of 3 sub-lethal blasts into a compressed air-driven blast chamber separated by 2 week intervals (n=11). Sham controls received anesthesia but without blast exposure (n=11). OF tests were performed 1 or 7 days after each blast using a computerized video tracking system in near-darkness to monitor spontaneous activity. Spatial and temporal variables calculated for both blast and sham groups were: Distance moved (cm) and time (s) spent in the center or periphery zones of the field, total distance traveled, speed in center and periphery zones, rearing events and non-linear regressions of distance moved and rearing events on time. Results showed that the sham group expressed the expected decrease (habituation) in total distance walked, and distance walked as well as speed in center and periphery in successive exposures to the OF while the blast group did not, a sign of impaired learning. The blast group also walked more and faster and demonstrated more rearing behavior, both considered OF signs of anxiety. These results indicate that OF outcomes of bTBI in animals have resemblance to alterations observed in human subjects with this condition and might be useful in evaluating the response of behavioral outcomes of bTBI to experimental treatments., (Published by Elsevier B.V.)

Cholinergic mechanisms are known to play a key role in cognitive functions that are profoundly altered in traumatic brain injury (TBI). The present investigation was designed to test the ability of continuous administration, starting at the time of injury, of physostigmine (PHY), an acetylcholinesterase (AChE) inhibitor that crosses the blood-brain barrier (BBB), to ameliorate the alterations of learning and memory induced by cerebral cortex impact injury in rats under isoflurane anesthesia. Learning and memory were assessed with the Morris water maze implemented during days 7-11 (WM1), and days 21-25 post-TBI (WM2), with four trials per day for 3 days, followed by target reversal and 2 additional days of training. These groups of Sprague-Dawley male rats were used: TBI treated with PHY at 3.2 μmol/kg/day (TBI-PHY3.2), or 6.4 μmol/kg/day (TBI-PHY6.4), by subcutaneous osmotic pumps, or TBI and no injury (Sham) treated with saline. AChE activity was measured in brain tissue samples of non-traumatized animals that received PHY at the doses used in the TBI animals. In WM1 tests, PHY3.2 improved learning within sessions, but not between sessions, in the recall of the target position, while PHY6.4 had no significant effects. In WM2 tests, PHY improved within- and between-sessions performance at both dose levels. We found that continuous AChE inhibition interacted with repeated training on the water maze task to completely reverse the deficits seen in learning and memory induced by TBI. The PHY treatment also reduced the amount of brain tissue loss as measured using cresyl violet staining.

Objective: This study aimed to compare calf tissue oxygenation responses to calf exercise in men without diagnosed peripheral arterial disease but with selected risk factors for peripheral arterial disease with those without risk factors., Design: A cross-sectional quasi-experimental design was used. The no-risk group (n = 20) had none of the risk factors (diabetes, hypertension, hyperlipidemia, obesity, current or 10 pack-yr smoking history, or age ≥65 yrs). The at-risk group (n = 45) had one to six risk factors. Medial calf tissue oxygenation (percentage saturation) was determined using near-infrared spectroscopy during seven consecutive 5-min test stages: rest, 0-W active plantar/dorsiflexion, rest, 4-W resistive plantar flexion, rest, 8-W resistive plantar flexion, and rest. Resistive exercise was performed on the Stresst'er calf ergometer., Results: Compared with the no-risk group, decrements in calf tissue oxygenation induced by light-to-moderate resistive calf exercise in the at-risk group was significantly greater (by 9% saturation) (4-W: P < 0.001; 8-W: P = 0.002)., Conclusions: Men with risk factors for developing peripheral arterial disease but without such diagnosis demonstrated greater decrements in calf tissue oxygenation during calf exercise compared with men without risk factors. Further development of this test may lead to early diagnosis and intervention to modify risk factors and prevent co-morbidities.

This randomized, controlled, multisite Department of Veterans Affairs clinical trial assessed robot-assisted (RA) upper-limb therapy with the Mirror Image Movement Enabler (MIME) in the acute stroke rehabilitation setting. Hemiparetic subjects (n = 54) received RA therapy using MIME for either up to 15 hours (low-dose) or 30 hours (high-dose) or received up to 15 hours of additional conventional therapy in addition to usual care (control). The primary outcome measure was the Fugl-Meyer Assessment (FMA). The secondary outcome measures were the Functional Independence Measure (FIM), Wolf Motor Function Test, Motor Power, and Ashworth scores at intake, discharge, and 6-month follow-up. Mean duration of study treatment was 8.6, 15.8, and 9.4 hours for the low-dose, high-dose, and control groups, respectively. Gains in the primary outcome measure were not significantly different between groups at follow-up. Significant correlations were found at discharge between FMA gains and the dose and intensity of RA. Intensity also correlated with FMA gain at 6 months. The high-dose group had greater FIM gains than controls at discharge and greater tone but no difference in FIM changes compared with low-dose subjects at 6 months. As used during acute rehabilitation, motor-control changes at follow-up were no less with MIME than with additional conventional therapy. Intensity of training with MIME was positively correlated with motor-control gains.

Objective: To establish whether muscle blood flow (MBF) measurements with O-water positron emission tomography could reliably identify patients with critical limb ischemia and detect and quantify a distal deficit in skeletal MBF in these cases., Design: O-water positron emission tomography scans were performed at rest or during unloaded ankle plantar and dorsiflexion exercise of the diseased leg in 17 subjects with leg ischemia or on a randomly selected leg of 18 age-matched healthy control subjects. TcPO2 was evaluated with Novametrix monitors and perfusion of skin topically heated to 44 degrees C and adjacent nonheated areas with a Moor Instruments laser Doppler imaging scanner., Results: The enhancement of MBF induced by exercise was significantly lower in ischemic than in normal legs, and the sensitivity and specificity of this phenomenon were similar to those of laser Doppler imaging or TcPO2 in identifying ischemia subjects. In addition, the exercise MBF deficit was predominant at the distal-leg levels, indicating the ability of the technique to help determine the correct level of amputation., Conclusions: Skeletal MBF of legs with severe ischemia can be detected accurately with O-water positron emission tomography and could add valuable information about viability of skeletal muscle in the residual limb when deciding the level of an amputation.

Objective: To determine and describe changes in weekly work, power, exercise times, and recovery times during an exercise training intervention in men with peripheral arterial disease (PAD) and intermittent calf claudication., Design: Tracking of weekly exercise training parameters involved repeated measures over time in one group of participants. Other outcomes of this pilot study used a one-group, pretest-posttest design., Setting: Tertiary-care medical center., Participants: Fifteen male veterans (mean age, 69 years) with Fontaine stage IIa PAD and classic intermittent calf claudication., Main Outcome Measurements: Participants completed graded treadmill exercise tests before and after intervention from which maximal walking power was calculated. Work, power, and exercise and recovery times for each exercise training session were computed and averaged for each week., Intervention: The intervention consisted of an intensive 3-month exercise training program involving walking and calf muscle exercises: 3 sessions per week at the clinic (treadmill walking and calf ergometry) and 2 sessions per week at home (free walking and standing heel raises)., Results: After training, participants increased treadmill maximal walking power from 220 to 414 W (by 87%). Treadmill and calf exercise work, power, and exercise time per session increased linearly during 13 weeks of training, whereas recovery time per session of treadmill exercise decreased. During the same period, treadmill and calf exercise training power outputs increased by averages of 227% and 92%, respectively., Conclusion: Calculation of work and power during exercise training can be used to track progress quantitatively at short intervals. Weekly linear increases in training work and power per exercise session suggest that optimal intervention duration may be longer than 3 months for men with PAD and intermittent calf claudication., (Copyright 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effects of exercise training on calf tissue oxygenation in men with peripheral arterial disease and intermittent calf claudication., Design: This pilot study was prospective and longitudinal and used a one-group, pretest-posttest design., Setting: Tertiary care medical center for veterans., Participants: Fifteen male veterans (mean age 69 years) with Fontaine stage IIa peripheral arterial disease and classic intermittent claudication., Main Outcome Measurements: Before and after intervention, participants performed graded treadmill exercise tests while medial calf tissue oxygenation (StO(2), % oxyhemoglobin saturation) was monitored continuously with near-infrared spectroscopy., Intervention: The intervention consisted of a 3-month exercise training program involving 3 sessions per week at the clinic (treadmill walking, calf ergometry) and 2 sessions per week at home (free walking, standing heel raises)., Results: After completion of the intervention, participants significantly increased their maximal treadmill exercise time from 7.19 to 11.27 minutes. Mean exercise StO(2) decreased from 29% to 19% saturation, StO(2) x time area increased from 421% * min to 730% * min StO(2) nadir, and StO(2) recovery time did not change significantly., Conclusions: After the exercise intervention, the improved treadmill walking performance was accompanied by greater calf tissue deoxygenation during exercise. Given the continued presence of ischemia, this finding may represent increased capillarization and diffusion-based enhancement of arteriovenous O(2) extraction.

Cerebral blood flow (CBF), a surrogate of neural activity in the identification of brain regions involved in specific functions, has been used in this report to trace the compensatory enhancement of activity in non-traumatized areas of the brain following a focal lesion. We have previously shown activation of CBF in the cortex contralateral to a focal contusion, 24 h after the event. The present report extends the characterization of this trans-hemispheric cortical blood flow activation by studying its time course and regional distribution from 4 days to 4 weeks post-trauma. Adult male Sprague-Dawley rats received a cortical impact through a 6.3 mm craniotomy under halothane anesthesia. CBF was measured with the quantitative autoradiographic (14)C-Iodoantipyrine technique, in conscious animals, 4 days, 2 weeks and 4 weeks post-trauma. CBF was severely decreased at the site of impact where necrosis developed later, and it remained depressed in the surrounding areas throughout the observation period. Trans-hemispheric CBF enhancement was maximal at 4 days and it returned to control levels 28 days post-trauma. This phenomenon was present in all cortical regions symmetrical to the impact zone, but also in auditory, visual, entorhinal and insular cortex. These results suggest that the participation of the contralateral cortex in the recovery from unilateral brain trauma is not limited to the regions homologous to those that received the impact. The time course of CBF changes was found to be consistent with the recovery of motor function in this model.

Objectives: To report normal values of skin perfusion in healthy subjects in three age groups using a laser Doppler imager; to determine differences attributable to gender, age, site, and use of red or near-infrared lasers; and to correlate transcutaneous oxygen with laser flux values., Design: Flux and transcutaneous oxygen were measured at ten sites in the lower extremity in 60 subjects from three age groups. Heated and unheated sites were scanned with red and near-infrared lasers., Results: Heat hyperemia was prominent at all sites. Small, statistically significant mean +/- SD differences were found between heated and nonheated sites for the red and near-infrared lasers (P = 0.02). All flux ratios were independent of gender but were higher in the oldest group. Plantar sites demonstrated higher flux in unheated areas and lower flux ratios compared with leg sites. Transcutaneous oxygen did not correlate significantly with flux for either laser type., Conclusions: Scanning laser-Doppler imaging flux values provide a reference for identifying patients at risk for tissue ischemia and poor healing potential caused by impaired circulatory reserve in the legs and distal feet. The lack of correlation between flux and transcutaneous oxygen in healthy individuals suggests that they measure different physiologic processes.

We studied 31 subjects with severe leg ischemia and 29 age-matched nonischemic control subjects to compare preamputation assessments of leg ischemia using laser Doppler imaging (LDI), transcutaneous partial pressure of oxygen (TcPO(2)), and transcutaneous partial pressure of carbon dioxide (TcPCO(2)). TcPO(2) and TcPCO(2) were evaluated with Novametrix Medical Systems, Inc, monitors (Wallingford, Connecticut) and perfusion (flux) of skin topically heated to 44 degrees C, and adjacent nonheated areas were evaluated with a Moor Laser Doppler Imager (Moor Instruments, Ltd; Devon, England). LDI flux of heated areas, its ratio to nonheated areas, and TcPO(2) (not TcPCO(2)) were lower in ischemic subjects than in control subjects. LDI flux ratio performed better than TcPO(2) in identifying ischemia, with fewer false positive and false negative results. Moreover, LDI flux of heated skin detected a proximal to a distal gradient of perfusion in ischemic subjects, while TcPO(2) did not. LDI was superior to TcPO(2) in discriminating correctly between ischemic and nonischemic skin. The results suggest that an LDI ratio below 5 indicates nonviable skin.

Study Design: A paired comparison of the peak and submaximal responses of oxygen uptake and heart rate in patients with spinal cord injury (SCI) performing voluntary arm cycle exercise and functional electrical stimulation (FES) leg cycling exercise., Objectives: To test if the blunted heart rate response and slower rate of adjustment of oxygen uptake seen in patients with SCI performing FES leg cycle exercise are also characteristic of arm exercise in these patients., Methods: Eight paraplegics performed incremental and constant work rate (CWR) exercise with the legs and arms. Mean response times (MRT) for Vo2 during exercise (on) and in recovery (off) were calculated from the breath-by-breath Vo2 profile., Results: Peak heart rate was higher during incremental arm exercise, and uncorrelated with that observed during incremental FES leg cycling. For the same increase in Vo2, constant work rate arm exercise was associated with faster (and normal) Vo2 kinetics, greater increase in heart rate, and lower end-exercise blood lactate, compared to FES leg cycling., Conclusions: The consistently higher peak heart rate and Vo2, and faster Vo2 kinetics, for voluntary arm compared to FES leg cycle exercise suggest no intrinsic dysfunction of heart rate control in these paraplegics. Rather, these data suggest that during FES leg cycling the changes seen are due to some characteristic specific to the injury, such as reduced muscle mass and/or deconditioning of the remaining muscle., Sponsorship: This research was supported by The Department of Veterans Affairs, Rehabilitation Research and Development Project #B603-RA. Spinal Cord (2000) 38, 340 - 345.

Objective: To determine the magnitude of changes in muscle mass and lower extremity body composition that could be induced with a regular regimen of functional electrical stimulation (FES)-induced lower-extremity cycling, as well as the distribution of changes in muscle mass among the thigh muscles in persons with spinal cord injury (SCI)., Study Design: Thirteen men with neurologically complete motor sensory SCI underwent a 3-phase, FES-induced, ergometry exercise program: phase 1, quadriceps strengthening: phase 2, progressive sequential stimulation to achieve a rhythmic pedaling motion (surface electrodes placed over the quadriceps, hamstrings, and gluteal muscles); phase 3, FES-induced cycling for 30 minutes. Participants moved from one phase to the next when they met the objectives for the current phase., Measures: Computed tomography of legs to assess muscle cross-sectional area and proportion of muscle and adipose tissue. Scans were done at baseline (before subjects started the program), at first follow-up, typically after 65.4+/-5.6 (SD) weekly sessions, and at second follow-up, typically after 98.1+/-9.1 sessions., Results: Increases in cross-sectional areas were found in the following muscles: rectus femoris (31%, p<.001). sartorius (22%, p<.025), adductor magnus-hamstrings (26%, p<.001), vastus lateralis (39%, p = .001), vastus medialis-intermedius (31%, p = .025). Cross-sectional area of adductor longus and gracilis muscles did not change. The ratio of muscle to adipose tissue increased significantly in thighs and calves. There was no correlation among the total number of exercise sessions and the magnitude of muscle hypertrophy., Conclusions: Muscle cross-sectional area and the muscle to adipose tissue ratio of the lower extremities increased during a regular regimen of 2.3 FES-induced lower extremity cycling sessions weekly. The distribution of changes was related to the proximity of muscles to the stimulating electrodes.

The purpose of this preliminary study was to describe pedal effectiveness parameters and knee-joint reaction forces generated by subjects with chronic spinal cord injury (SCI) during functional electrical stimulation (FES)-induced bicycling. Three male subjects (age 33-36 years old), who were post-traumatic SCI (ASIA-modified level A, level T4-C5) and enrolled in an FES rehabilitation program, signed informed consent forms and participated in this study. Kinematic data and pedal forces during bicycling were collected and effective force, knee-joint reaction forces, knee generalized muscle moments, and knee-joint power and work were calculated. There were three critical findings of this study: 1) pedaling effectiveness was severely compromised in this subject population as indicated by a lack of overall positive crank work; 2) knee-joint kinetics were similar in magnitude to data reported for unimpaired individuals pedaling at higher rates and workloads, suggesting excessive knee-joint loading for subjects with SCI; and 3) shear reaction forces and muscle moments were opposite in direction to data reported for unimpaired individuals, revealing an energetically unfavorable knee stabilizing mechanism. The critical findings of this study suggest that knee-joint kinetics may be large enough to produce a fracture in the compromised lower limbs of individuals with SCI.

Objective: To test the hypothesis that the limitation in muscle power development with functional electrical stimulation (FES) results from an insufficient increase in muscle blood flow (MBF) in response to activity., Subjects and Methods: Five subjects with neurologically complete spinal cord injury (SCI) were tested to measure the MBF response to FES-induced knee extension. The MBF response to voluntary knee extension was measured in five age-matched, able-bodied controls. MBF was measured with positron emission tomography (PET) using H2(15)O as a tracer. Three scans were performed with muscle at rest (baseline), immediately after 16min of FES-induced or voluntary knee extension (activity), and 20min after the second scan (recovery)., Results: In SCI subjects, mean +/-SE MBF (mL/100g/min) values were: baseline = 1.85 +/- .48; post-FES = 31.9 +/- 5.65 (p = .0058 vs baseline); recovery = 6.06 +/- 1.52 (p = .0027 vs baseline). In able-bodied controls, mean +/-SE MBF values were: baseline = 8.52 +/- 3.24, post-voluntary exercise = 12.62 +/- 3.03 (p = .023 vs post-FES in SCI subjects); recovery = 10.7 +/- 6.01., Conclusions: MBF does not appear to be the limiting factor in muscle power generation with FES. The greater increase in MBF observed with FES in SCI subjects when compared with able-bodied subjects performing a similar task (unloaded knee extension against gravity) may relate to abnormal metabolism in FES-stimulated muscle.

Objectives: (1) To determine if a hybrid exercise (leg plus arm) training program performed immediately after functional electrical stimulation (FES) leg cycle exercise (LCE) training would further improve aerobic capacity when compared with FES leg cycle training alone, and (2) to compare the submaximal responses occurring during both FES-LCE alone and hybrid exercise in the same SCI subjects., Design: Nonrandomized control trial whereby subjects act as their own control., Setting: Outpatient rehabilitation in a primary care hospital., Patients: A volunteer sample (n = 11) of men 20 to 50 years old with complete spinal cord injury, free from cardiovascular and metabolic disease with spasticity., Interventions: Three phases of exercise training: phase I, progressive FES-LCE to 30 minutes of exercise (n = 11); phase II, 35.2 +/- 16.2 sessions of FES-LCE (n = 11); phase III, 41.4 +/- 17.7 30-minute sessions of hybrid exercise (n = 8)., Main Outcome Measures: (1) Aerobic capacity-a further increase after hybrid exercise when compared with FES-LCE alone; (2) submaximal physiologic parameters (oxygen uptake [VO2], heart rate [HR], blood lactate [BLa-])-measurement of these during constant work rate exercise and a training effect., Results: VO2 (the body's ability to utilize oxygen) significantly improved (p < .05) after both FES-LCE and then further after hybrid training. Hybrid exercise training resulted in significantly (p < .05) greater work rates and VO2 values than both FES-LCE at baseline and training work rates., Conclusion: These subjects demonstrated that hybrid exercise performed twice a week provided sufficient intensity to improve aerobic capacity and provide a medium whereby patients with SCI can burn more calories than via FES-LCE alone. This has important implications for improving the health and fitness levels of individuals with SCI and may ultimately reduce their risk of cardiovascular disease.

The ability of central cholinesterase inhibition to improve cerebral blood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral cortex. The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.

We examined the ability of patients with spinal cord injury to undergo adaptations to chronic exercise training (cycle ergometry) invoked by functional electrical stimulation (FES) of the legs. Nine such patients performed incremental and constant work rate exercise before and after exercise training. Exercise sessions averaged 2.1 +/- 0.4/wk, and consisted of 30 min/session of continuous FES recumbent cycling with increasing work rate as tolerated. Peak VO2 and peak work rate significantly improved with training. Peak VO2 was significantly correlated with peak heart rate both before and after training (r = 0.97 pre and 0.85 post, P < 0.01 for both). The time course of the VO2, VCO2 and VE responses to constant-load exercise (unloaded cycling) and in recovery (mean response time MRT) were very long prior to training, and became significantly faster following training. However, there was no correlation between percentage improvement in either MRTon or MRToff for VO2 and the percentage increase in peak VO2. Exercise tolerance in these patients with spinal cord injury appears to be a direct function of the ability to increase heart rate. Further, exercise training can elicit significant improvements in both exercise tolerance and in gas exchange kinetics, even when performed only twice per week. However, these improvements may be accomplished by different mechanisms.

Spinal cord-injured (SCI) patients are at increased risk for fractures secondary to neurogenic osteoporosis. Earlier research claimed physical conditioning resulted in a decreased incidence or reversal of neurogenic osteoporosis. This study evaluated the effects of functional electrical stimulation-induced lower extremity cycling (FESILEC) on the bone densities of SCI patients using dual-energy x/ray absorptiometry (DEXA). The study consisted of 12 healthy male SCI patients, aged 23 to 46 (x +/- SD, 34 +/- 6) yr. The patients were post-traumatic, complete, spastic SCI; time postinjury ranged from 2 to 19 (9.7 +/- 5.1) yr. Patients participated in a three-phase training program. Phase 1 consisted of quadriceps strengthening. Phase 2 consisted of progressive sequential stimulation of quadriceps, hamstrings, and gluteal muscles, achieving a rhythmical pedaling motion on the REGYS I ergometer. Phase 3a consisted of 30-min FESILEC sessions. DEXAs were done at baseline and at completion of Phase 3a and Phase 3b. Bone densities were done of the lumbar spine levels 2-4 (L2-4), bilateral trochanters (T), Ward's triangles (WT) and femoral necks (FN). Baseline bone density indicated no difference between L2-4 of ambulatory males and SCI males. Baseline values obtained for T, WT, and FN were, respectively, 71, 82, and 79% of ambulatory values. Results after completion of the Phase 3a training program indicated no statistically significant difference compared with baseline values. There was, however, a positive trend in the lumbar spine post-Phase 3a (L2-4, P=0.056). Eight patients continued the exercise program, using a combination of upper and lower extremity cycling (Phase 3b) for a longer period of time (25 +/- 9 wk). DEXAs done after Phase 3b indicated no change relative to baseline data or data post-Phase 3a. In conclusion, although FESILEC did not significantly increase bone density in the hip parameters of chronic SCI patients, a positive trend was observed in the lumbar spine. Further research with acute intervention, such as FESILEC during the first few months post-SCI, is warranted to further evaluate a treatment regimen to prevent or reduce neurogenic osteopenia.

Eight males with spinal cord injury (SCI) participated in an exercise training program using neuromuscular electrical stimulation (NMES) leg cycle ergometry. Each subject completed a minimum of 24 (mean +/- SD = 38.1 +/- 17.2) 30-minute training sessions over a 19-week period. The initial work rate (WR) of 0 watts (W) of unloaded cycling was increased when appropriate with subjects exercising at 11.4 +/- 3.7 W (range = 6.1 W-18.3 W) at the end of the training program. Randomized block repeated measures ANOVA was used to compare pretraining and posttraining peak physiologic responses during graded NMES leg cycle tests and subpeak physiologic responses during 10 minutes of NMES leg cycle exercise at an absolute WR (0 W). A significant (P < or = 0.05) increase was observed for peak VO2; (+10%, 1.29 +/- 0.30 to 1.42 +/- 0.39 1.min-1). No other statistically significant differences were noted for any other peak variable (VCO2, VO2 ml.kg-1 min-1, VE, WR, HR, RER) pre- to posttraining. During submaximal NMES leg cycle testing, a significant decrease was noted for RER (-9.2%, 1.19 +/- 0.14 to 1.08 +/- 0.09). No other submaximal variable (VO2 1.min-1, ml.kg-1.min-1, VCO2, HR, VE) showed significant changes as a result of the training. Although the improvement in peak VO2 was not as dramatic as those reported in previous studies, it appears that NMES leg cycle training performed two times per week can significantly enhance cardiorespiratory fitness.

We examined the kinetics of VO2, VCO2, and VE following the onset of unloaded leg cycling, and in recovery, in six patients with spinal cord injury (SCI). Exercise was produced by functional electrical stimulation (FES) of the quadriceps, hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l.min-1), VCO2 (1.20 +/- 0.22 l.min-1) and VE (41 +/- 10 l.min-1) were elevated compared to values typically seen in healthy ambulatory subjects performing similar unloaded cycling. Mean response times for the on transients (MRTon) were both long and variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and VE (202 +/- 61 s). Recovery kinetics showed much less intersubject variability, and for five of six subjects were faster than the equivalent exercise MRT for all three variables (MRToff for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and VE 144 +/- 34 s), but P > 0.05 for all three. Size of the O2 deficit (1.96 +/- 0.90 l) and end-exercise lactate (7.05 +/- 1.65 mmol.l-1) were similar to values reported for healthy sedentary subjects performing maximal voluntary exercise, but the end-exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity of exercise. In conclusion, FES-induced unloaded cycling leads to exaggerated responses of pulmonary gas exchange and long time constants in patients with SCI. The delayed kinetics may be due in part to a blunted increase in heart rate in addition to severe deconditioning.

A unique case of knee extension contracture resulting from acute pelvic venous thrombosis is presented. Magnetic resonance imaging/angiography and electrodiagnosis aided in understanding the pathogenesis and hence in designing the treatment. Neuropathies contributed to the severity of the problem. Physical treatment to ease the edema improved knee joint range of motion but did not fully restore knee flexion.

Forty six patients that underwent below knee amputation for diabetes, trauma/osteomyelitis or peripheral vascular disease were studied. Healing was estimated by the rate of progression through temporary prostheses as determined weekly by the amputee rehabilitation team (physiatrist, orthopedist, physical therapist, nurse, and prosthetist). For all groups combined, mean days +/- standard error from amputation to above knee cast with pylon and foot (AKPy) were 22.9 +/- 1.9, to below knee cast with pylon and foot (BKPy) 41.6 +/- 2.8 and to laminated temporary prostheses 66.5 +/- 4.5. A regression analysis of these variables on age (range: 29 to 84 yr) showed significant positive correlations for AKPy (r = 0.34, P = 0.0214) and BKPy (r = 0.40, P = 0.0056). An analysis of variance with contrasts (Tukey's protected t) showed significant lower values (P < 0.05) for amputation to BKPy in the trauma/osteomyelitis group when compared to diabetes or peripheral vascular disease and no difference among the last two groups. However, when variables were adjusted for age (analysis of covariance with age as a covariate), the differences among groups disappeared (covariance F(2,44) = 0.9, P > 0.4). In conclusion, age, not the cause of the amputation, correlated with healing after below knee amputation as estimated by the rate of progression through temporary prostheses.

This study was conducted to determine the feasibility of quantifying spasticity by measuring the resistance to passive movement using an isokinetic dynamometer. A quantifiable method was developed by determining the summation of the four consecutive resisting torque amplitudes during flexion and extension of the knee at specified speeds and range of motion. A more rigorous assessment was made by finding the slope of the linear regression curve of torque-velocity data. Although the values of maximum torque were higher in the spastic group than in the normal group, the difference was statistically significant only when the sum of the torque amplitudes was considered (P < 0.0028). Values of the maximum torque as well as the sum of the torque amplitudes increased in a linear fashion (r > 0.75) with increasing velocity. The slopes of the torque-velocity curves were greater in spastic subjects than in normal subjects. The sensitivity to the rate of stretch was statistically greater (P < 0.0004) for the spastic group than normals only when the sum of torque amplitudes was considered. The corresponding data obtained during the flexion and extension of the knee were not statistically different (P > 0.05). Serial summation of torque amplitudes and measurement of slope in the torque-velocity curve are sensitive and repeatable methodologies for the measurement of spasticity assessment.

The cerebrovascular and metabolic effects of the novel cholinesterase inhibitor eptastigmine were tested in conscious rats. The drug was administered by single intravenous injection, and blood flow or glucose utilization were assessed in 38 brain regions by quantitative autoradiographic techniques. A dose-dependent increase in regional cerebral blood flow (rCBF) was obtained for i.v. doses ranging from 0.5 to 3 mg kg-1. Forty minutes after the dose of 1.5 mg kg-1, average rCBF of the 38 regions studied was (mean +/- SD) 2.62 +/- 0.62 ml g-1 min-1, a value significantly higher than that of saline-injected controls (1.46 +/- 0.26; p < 0.005). In contrast, a similar dose of eptastigmine did not significantly alter regional cerebral glucose utilization (rCGU) (0.90 +/- 0.21 mumol g-1 min-1) when compared with saline-injected controls (0.99 +/- 0.08 mumol g-1 min-1). A linear correlation between rCBF and rCGU was observed both in saline (r = 0.871) and eptastigmine (r = 0.873)-injected animals but the slope of the regression line of rCBF on rCGU was significantly higher (p < 0.01) in the eptastigmine group (2.863 +/- 0.266) than in the controls that received saline (1.00 +/- 0.094). The cerebral vasodilatation induced by eptastigmine peaked at 40 min after drug administration. No toxic signs were observed at the doses used. Mean arterial blood pressure decreased after 0.5 mg kg-1 (control = 109.3 +/- 10.56 mm Hg; eptastigmine = 96.6 +/- 8.10 mm Hg) but did not differ from control at the higher doses. It is concluded that eptastigmine induces a long-lasting increase in rCBF and a significant enhancement of the rCBF:rCGU ratio in most regions. The results suggest an important role of endogenous acetylcholine in the control of cerebral perfusion.

The effect of "standing" in a frame on spasticity (clinical assessment and H-reflex), contracture (lower extremity joint range of motion), and osteoporosis (dual photon absorptiometry) was studied in six paralyzed males (mean age 49 yr) who had been confined to wheelchairs for an average of 19 years. Standing time averaged 144 hours over a mean of 135 days. Clinical Assessment measured reflexes, tone, and clonus in the legs. Results revealed no important differences between initial and final scores for clinical assessment and joint range of motion. In three subjects for whom H-reflexes were found, latency and amplitude were not altered by "standing." Bone density was normal in the lumbar spine but significantly reduced in the femoral neck. "Standing" did not modify the bone density in any site. A follow-up interview revealed that 67% of subjects continued to "stand" and felt healthier because of it. In summary, "standing" had no ill effects, did not alter measured variables, and had a positive psychological impact.

The long-term effects of spinal cord ischemia were studied in 21 rats by lesion scores (LS, n = 21), somatosensory evoked potentials (SEP, n = 16), electromyographic measurements (EMG, n = 12) and histology of the spinal cord (n = 21) 48.5 +/- 57.2 days after 10- to 12-min occlusion of the thoracic aorta and subclavian arteries. All the animals were initially paraplegic with a spastic presentation but seven recovered within 2 days (group A), demonstrating low LS (3.4 +/- 1.05) normal EMGs (n = 3) and unremarkable histology. The 14 paraplegic animals presented relevant findings of the lumbar cord consisting of white matter lesions only (group B, n = 7) or white and gray matter lesions (group C, n = 7). Group B animals showed severe deficit (LS = 11.8 +/- 2.93) without denervation on EMG (n = 5) or muscle atrophy on histology. Group C animals displayed equal impairment (LS = 14.4 +/- 0.71), denervation on EMG (n = 4), and muscle atrophy. Resting motor unit activity of groups B and C were significantly different from group A (p < 0.001), while LS of groups B and C did not differ (p = 0.083). These data underscore the nature and the extent of white matter lesions during spinal cord ischemia, a finding which has generally been eclipsed by emphasis on gray matter lesions in previous studies.

The effect of intravenous physostigmine on cerebral perfusion of patients with cortical stroke was investigated using hexamethyl-propyleneamine oxime (HMPAO) single-photon emission computed tomography. Each patient was studied twice, afteran intravenous infusion of either 1 mg of physostigmine salicylate or saline. A marked increase in HMPAO activity was observed in all regions of post-physostigmine scans when compared to the corresponding post-saline scans, except for the area of infarction and its mirror area in the contralateral hemisphere. In conclusion, physostigmine improves perfusion in the area of penumbra of patients with cortical infarction., (Copyright © 1992 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The present investigation was designed to determine the effect of lesions localized to the nucleus basalis/substantia innominata (NB) on resting and cholinergically activated regional cerebral cortical blood flow (rCBF). Ibotenic acid (10 micrograms) was infused locally at 1 mm caudal to bregma, 3 mm lateral to the midline, and 8 mm below the cortical surface. Effectiveness of lesions was demonstrated by histological verification of lesion sites and determination of choline acetyltransferase activity in cerebral cortex homogenates. rCBF was measured with the autoradiographic iodo-14C-antipyrine technique. Resting rCBF was similar in the hemisphere that received the NB lesion and in the contralateral (intact) side in all regions examined. Physostigmine intravenous infusion (3.3 micrograms.kg-1.min-1) enhanced rCBF in frontal, parietal, occipital, and temporal cortex. The increase was symmetrical, however, indicating inability of NB lesion to affect this phenomenon. It is concluded that the cortical cholinergic afferents originating in the NB are not involved in the control of rCBF.

Spinal cord glucose utilization (SCGU) of gray and white matter was studied with the quantitative autoradiography [14C]2-deoxyglucose methodology, below and above a complete low thoracic transection. One day after transection, a generalized decrease in SCGU was observed in gray matter, particularly marked in the dorsal horn of the lumbar cord. A progressive increase in SCGU was observed thereafter. Values reached levels greater than those of non-transected controls by 2 and 4 weeks after the intervention in ventral horn of the lumbar cord, and ventral and dorsal horn of the cervical cord. A similar behavior of SCGU was observed in white matter of transected animals. The development of 17 lumbar reflex modalities was quantified between days 1 and 28 after spinal transection. The delay in emergence of these reflexes was related to their complexity. Correlation of reflex scores with SCGU was significant for all lumbar cord regions but linearity of this relationship was only observed in white matter. These results uncover a close relationship between SCGU and reflex activity of the spinal cord below a complete transection, particularly striking in white matter and suggests a role of the fasciculi proprii of the spinal cord in this phenomenon.

3H-labeled physostigmine (50 micrograms.kg-1) was administered intravenously to rats, and its concentration in brain tissue and spinal cord was assessed by quantitative autoradiography. Regional cerebral blood flow (rCBF) was measured with iodo-14C-antipyrine autoradiography in control rats and in animals injected i.v. with a dose of physostigmine similar to that used for the distribution studies. Tissue concentration of 3H-physostigmine was correlated with rCBF for 37 brain regions. A high degree of correlation was found at 0.5 min after drug injection, r (correlation coefficient) = 0.87. This association decreased at later times (5 min r = 0.73, 12 min r = 0.24). Structures with high cholinesterase activity (caudate-putamen, amygdala, hippocampus) showed greater retention of physostigmine over time. The highest initial physostigmine concentrations were found in regions lacking a blood-brain barrier (pineal bland, median eminence, choroid plexus) (range = 10.4-23.8 nCi/mg) and the lowest in white matter (corpus callosum, internal capsule, hippocampus commisure, spinal cord dorsal column) (range = 1.2-2.6 nCi/mg). Initial concentrations of the drug in the areas in which physostigmine induced vasodilatation (motor, sensory, temporal and occipital cortex, claustrum, and superior collicullus) were not different from concentrations in areas of comparable basal rCBF in which no such effect was observed. Variations in drug access to brain regions, then, do not explain the topographical variations of the cerebrovascular action of physostigmine.

Cerebral cortical ischemia was induced in anesthetized rats by occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured with the H2 clearance technique in the center and periphery of the ischemic territory. A decrease of CBF to about 50% of pre-occlusion values was observed in both areas. Administration of Physostigmine, a cholinesterase inhibitor, at a dose of 0.15 mg/Kg by intravenous route, induced an increase of CBF in the ischemic cortex. This change in CBF reached 120% of pre-occlusion level in the periphery and 80% of pre-occlusion value in the center of the area of distribution of the occluded artery. Although Physostigmine induced an increase in arterial blood pressure, the cerebral hyperemia observed both in normal and ischemic cortex could still be demonstrated after blockade of the pressor effect by bleeding or Phentolamine administration.

Survival under hypoxia (5% O2; 95% N2) was tested in mice 1 day to 50-weeks-old. Survival Rate (ratio of number of animals that survived 30 min under 5% O2 to total number of animals exposed) and the time from onset of exposure until the last gasp (Survival Time) were maximum in newborn animals and decreased as a function of age. Survival Rate and Survival Time were strongly influenced by drugs affecting cholinergic transmission. Atropine decreased the high survival under hypoxia of 1-week-old mice in a dose-related manner. Physostigmine increased survival under hypoxia in mice 3 to 50-weeks-old. This effect was not related to a peripheral action of the drug since it was not mimicked by neostigmine, a cholinesterase inhibitor without central actions. Moreover, peripheral cholinergic blockade with glycopyrrolate, a quaternary cholinergic blocker, did not prevent the protective effect of physostigmine. Since atropine impairs the ability of very young mice to survive hypoxia and physostigmine improves survival at later ages, it is concluded that a central cholinergic mechanism, possibly related to blood flow regulation, plays a significant role in the acute adaptation to hypoxia.

Inhibition of central nervous system cholinesterase with a single pulse of physostigmine induces a pronounced increase of blood flow in the neocortex, cingulate gyrus, claustrum, and amygdala. This phenomenon is not accompanied by an increase in energy metabolism and may help explain the effect of this drug on memory in normal humans and patients with Alzheimer's disease, as well as other conditions. In contrast, a parallel increase of blood flow and metabolism was observed in the superior colliculus, a component of the visual pathways. Prolonged administration of physostigmine lead to persistent vasodilatation in the neocortex, a lessening of this effect in cingulate gyrus, claustrum and amygdala, and an increase in primary olfactory cortex and hippocampus when compared with single pulse administration. Effects of physostigmine on glucose utilization remained essentially the same as with pulse administration.

Physostigmine, at 0.1, 0.2 and 0.3 mg/kg, was tested for effect on the survival of mice exposed to 5% O2-95% N2. Some treated animals survived for one hour under the hypoxic atmosphere (2 out of 14 at 0.1 mg/kg and 8 out of 28 at 0.2 and 0.3 mg/kg), an event never observed in untreated controls. The physostigmine-treated animals that died before the hour showed a dose-related increase in survival time from 4.3 min (untreated controls) to 27.6 min (0.3 mg/kg physostigmine). The effect of physostigmine may be related to its reported ability to increase cerebral blood flow and decrease cerebral oxygen consumption