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A precision isotonic measuring system for isolated tissues.

An isotonic measuring system is described which utilizes an angular position transducer of the linear differential voltage transformer type. Resistance to corrosion, protection against the ingress of solutions, and ease of mounting and setting up were the mechanical objectives. Accuracy, linearity, and freedom from drift were essential requirements of the electrical specification. A special housing was designed to accommodate the transducer to overcome these problems. A control unit incorporating a power supply and electronic filtering components was made to serve up to four such transducers. The transducer output voltage is sufficiently high to drive directly even low sensitivity chart recorders. Constructional details and a circuit diagram are included. Fifty such transducers have been in use for up to four years in these laboratories. Examples of some of the published work done using this transducer system are referenced.

Animals↗

Progression of venoconstriction in patients after heart transplantation during exercise.

Changes of both central hemodynamics and peripheral circulation in non-exercising muscle were investigated in 17 patients after successful orthotopic heart transplantation during moderate supine isotonic leg-exercise. Changes of peripheral circulation were measured in 14 healthy controls. The cardiac output rose from 5.71 to 9.45 l/min, the right atrial pressure from 3.5 to 12 mmHg, mean pulmonary arterial pressure from 17.4 to 36.9 mmHg, and pulmonary capillary wedger pressure from 9.5 to 23.5 mmHg. Venoconstriction, already present in the rest in patients after heart transplantation, further increased during the exercise (venous compliance lowered from 0.0454 to 0.0309 ml/mmHg). In controls no changes were observed (venous compliance being 0.0833 at rest and 0.0839 ml/mmHg during exercise). Negative correlation was found between an increase in pulmonary arterial pressure and a decrease in venous compliance. The authors hypothesise that venoconstriction could serve to increase of cardiac output via Frank-Starling mechanisms in patients after heart transplantation. Forearm blood flow during the exercise decreased (from 3.4 to 2.0 ml/100 ml/min), while local peripheral resistance rose (from 35.9 to 78.8 units) in patients after heart transplantation. These changes were not observed in controls.

Adult↗

Neural modulation of muscle contractile properties during fatigue: afferent feedback dependence.

H reflex amplitudes, an indirect measure of the excitability of the alpha motoneuron pool, were recorded from 10 males during fatigue induced by submaximal, isotonic, voluntary contractions of the soleus muscle. H reflex changes were correlated with electromyographic changes (mean power frequency (MPF); root mean square (rms EMG)), under ischemic and non-ischemic conditions. The purpose of the ischemia was to block transmission of Ia and possibly Ib afferents to assess whether changes in sensory feedback had any effect on alpha motoneuron and EMG activity during fatigue. Significant interactions were found between ischemic and non-ischemic conditions. After an initial decrease (1.21 +/- 0.56 mV to 0.54 +/- 0.39 mV), H reflex amplitudes increased during non-ischemic trials (0.54 +/- 0.39 mV to 1.13 +/- 0.84 mV). Under ischemic conditions H reflex amplitudes decreased (2.11 +/- 1.10 mV to 0.70 +/- 0.74 mV; P < 0.003). During non-ischemic conditions, MPF decreased across 5 consecutive trials (157.7 +/- 17.9 Hz to 124.7 +/- 17.2 Hz), as compared to an increase under ischemic conditions (132.8 +/- 21.2 Hz to 197.1 +/- 53.6 Hz; P < 0.001). Root mean square amplitude decreased during the non-ischemic trials (31.07 +/- 14.62 mV to 25.98 +/- 8.26 mV). A greater decrease was noted during the ischemic trials (34.00 +/- 23.61 mV to 4.95 +/- 3.77 mV; P < 0.001). Data suggest that the CNS modulates muscle contraction in order to preserve force output and neuromuscular transmission during fatigue. This modulation appears dependent on Ia and/or Ib afferent feedback.

Adult↗

The influence of isotonic exercise on cardiac hypertrophy in arterial hypertension: impact on cardiac function and on the capacity for aerobic work.

Intense physical training through isotonic exercises has controversial effects in individuals with moderate to severe hypertension. In this study, normotensive Wistar rats and rats with renovascular hypertension (Goldblatt II) were subjected to intense physical exercise involving two 50-min swimming sessions per day for a period of 12 weeks. At the end of the study, we evaluated the effect of training on arterial pressure, the capacity for aerobic work and cardiac function. Our results demonstrate that intense physical training has no effect on the arterial blood pressure of normotensive rats or of animals with moderate renovascular hypertension. Hypertensive animals with cardiac hypertrophy require a greater period of training in order to attain the same capacity for aerobic work as normotensive rats. This difference may result from an inability of the former animals to increase cardiac compliance, thereby impeding more extensive usage of the Frank-Starling mechanism to subsequently increase the systolic cardiac performance. Cardiac hypertrophy induced by exercise did not summate with that induced by arterial hypertension. Physical exercise normalized the end-diastolic left ventricular pressure in hypertensive animals without any corresponding increase in the compliance of the chamber. The first derivative of left ventricular pulse pressure (+/- dP/dt) was greater in the hypertensive trained group than in the hypertensive sedentary rats. These observations suggest that a systolic dysfunction of the left ventricle involving an elevated residual volume secondary to arterial hypertension may be corrected by physical exercise such as swimming.

Aerobiosis↗

Physiologic correlates of the heart rate response to upright isotonic exercise: relevance to rate-responsive pacemakers.

Rate-responsive cardiac pacing requires a sensitive physiologic variable that is closely correlated with the heart rate-oxygen uptake relation, particularly in patients with heart failure whose cardiac output response to exercise is more dependent on heart rate. Accordingly, the heart rate response to upright exercise was measured in 81 patients with heart failure or hypertension, or both, and in 27 normal subjects. Oxygen uptake (VO2), minute ventilation (VE), cardiac output, right heart pressures and the mixed venous temperature, oxygen saturation (SvO2) and pH were analyzed throughout exercise. Linear regression analysis of these variables with heart rate revealed the following: 1) There was a highly linear heart rate-VO2 relation in each subject (the average slope of this relation was greater [p less than 0.05] in patients with more severe failure). 2) VE was highly correlated with exercise heart rate, and its slope was not different between normal subjects and patients. 3) Mixed venous temperature and pH were poor predictors of exercise heart rate, particularly at low or moderate levels of work; however, SvO2 was highly correlated with heart rate for all levels of work. Thus, in normal subjects and patients with heart failure or hypertension, or both, heart rate increases linearly with isotonic leg exercise. Minute ventilation and mixed venous oxygen saturation are highly correlated with this response and may serve as potential sensors for rate-responsive pacemakers.

Adult↗

Association of vasoactive intestinal peptide with polymer-grafted liposomes: structural aspects for pulmonary delivery.

A polymer-grafted liposomal formulation that has the potential to be developed for aerosolic pulmonary delivery of vasoactive intestinal peptide (VIP), a potent vasodilatory neuropeptide, is described. As VIP is prone to rapid proteolytic degradation in the microenvironment of the lung a proper delivery system is required to increase the half-life and bioavailability of the peptide. Here we investigate structural parameters of unilamellar liposomes composed of palmitoyl-oleoyl-phosphatidylcholine, lyso-stearyl-phosphatidylglycerol and distearyl-phosphatidyl-ethanolamine covalently linked to polyethylene glycol 2000, and report on VIP-lipid interaction mechanisms. We found that the cationic VIP is efficiently entrapped by the negatively charged spherical liposomes and becomes converted to an amphipathic alpha-helix. By fluorescence spectroscopy using single Trp-modified VIP we could show that VIP is closely associated to the membrane. Our data suggest that the N-terminal random-coiled domain is embedded in the interfacial headgroup region of the phospholipid bilayer. By doing so, neither the bilayer thickness of the lipid membrane nor the mobility of the phospholipid acyl chains are affected as shown by small angle X-ray scattering and electron spin resonance spectroscopy. Finally, in an ex vivo lung arterial model system we found that liposomal-associated VIP is recognized by its receptors to induce vasodilatory effects with comparable high relaxation efficiency as free VIP but with a significantly retarded dilatation kinetics. In conclusion, we have designed and characterized a liposomal formulation that is qualified to entrap biologically active VIP and displays structural features to be considered for delivery of VIP to the lung.

Administration, Inhalation↗

Effects of changes in pH on the afferent impulse activity of isolated cat muscle spindles.

Muscle spindle activity has been shown to decrease in the sustained contracting muscle. The effect has been assumed to result from a declining fusimotor drive. Since accumulation of metabolites including H(+), lactate and CO(2) might also affect the receptor in the fatiguing muscle, the impulse activity of muscle spindles isolated from the cat tenuissimus muscle was characterized under varying degrees of extracellular pH, thus excluding any effect on fusimotor activity, blood supply and extrafusal muscle fibers. The isolated receptor was exposed to bathing fluids of pH 6.4, 7.4 and 8.4, and afferent discharge activity was recorded from the spindle nerve. Both primary and secondary endings responded similarly to changes in pH. Resting discharge frequency usually decreased with decreasing pH and increased with increasing pH. A sudden break-off in activity was observed with about 40% of primary endings and about 30% of secondary endings at pH 6.4. Experiments with slow stretch stimulation indicated that this effect was caused by a rising threshold of firing at the encoder site of the endings. With brief ramp-and-hold stretches, we tested the effects of changes in pH on the dynamic and static sensitivity of primary and secondary endings. When pH was reduced from 7.4 to 6.4, the initial burst activity at the beginning of the ramp phase increased in primary and secondary endings and the dynamic response increased in secondary endings, demonstrating that the dynamic properties of muscle spindle endings were usually augmented in the acidic milieu. The static properties rose as well because the static index of both types of ending increased significantly. By contrast, dynamic and static properties of both primary and secondary endings decreased significantly, when pH was increased from 7.4 to 8.4. The amplitude of tension that was measured during the passive stretch stimuli very slightly decreased in the acidic solution and very slightly increased in the alkaline solution. The decrease in the resting discharge activity at low pH supports those previous observations, which demonstrate a reduced peripheral input from muscle spindle afferents to the spinal motor nuclei during fatigue in the isometric contracting muscle. The present finding indicates that an attenuated afferent discharge is not only caused by a decreasing central activation of gamma-motorneurons, but may additionally be supported by a direct effect of protons on the muscle receptor itself. The accompanying augmentation of stretch sensitivity is suggested to correspond to the well-known increase in physiological tremor during exhaustive exercise.

Animals↗

The effect of a passive muscle stretching protocol on the articular cartilage.

OBJECTIVE: The aim of this study is to evaluate the articular cartilage alterations of rat ankles, after applying unilateral cyclic passive muscle stretching protocol in previously immobilized rats. METHODS: Twenty-two male albino rats divided into four groups, I--immobilized; IS--immobilized and stretched; S--stretched and C--control, were used in this experiment. The I and IS groups were immobilized for 4 weeks. In the muscle stretching protocol the treated ankle joint (groups IS and S) was manually full dorsal flexed 10 times for 60s with a 30s interval between each 60s period, 7 days a week for 3 weeks, to stretch the ankle plantar flexors muscle group. The right hind limb was free to move. At the end of the experiment, the ankles were removed, processed in paraffin and stained with hematoxylin-eosin and Safranin-O. Two blinded observers evaluated cellularity, chondrocyte cloning and Safranin-O staining through light microscopy. And a morphometric study was carried out using a hand count of chondrocyte cells and cartilage thickness measurement. RESULTS: No significant effect of solely muscle stretching concerning cellularity, chondrocyte cloning and Safranin-O staining parameters was detected. However, IS group presented a significantly higher reduction of proteoglycans content than the solely stretched and solely immobilized groups and the morphometric analysis showed significant cellularity increase without thickness alteration compared to control. CONCLUSIONS: These findings suggest that the stretching protocol used was harmful to the previously immobilized articular cartilage. However, the same stretching protocol did not harm the cartilage of non-immobilized groups.

Animals↗

Reliability of isokinetic measurements of ankle dorsal and plantar flexors in normal subjects and in patients with peripheral neuropathy.

OBJECTIVE: To establish a reliable method for evaluation of motor performance of ankle dorsal and plantar flexors in healthy subjects and in patients with peripheral neuropathy. DESIGN: Thirty-eight control subjects and 7 patients with peripheral neuropathy were studied. All patients and 25 control subjects were test twice. PATIENTS AND CONTROL SUBJECTS: An outdoor clinic sample of 7 patients with hereditary motor sensory neuropathy (HMSN) and 38 control subjects. MAIN OUTCOME MEASURES: The effect of a rest interval, a displacement of the axis of rotation, examination by three investigators on the peak torque and work of dorsal and plantar flexors, and the percentage difference at test-retests. RESULTS: Control subjects had percentage differences of 5.6% and 8.0% for dorsal flexion and 3.8% and 8.7% for plantar flexion at 60 degrees/sec and 180 degrees/sec, respectively. In neuropathic patients the percentage differences were 0% and 8.6% for dorsal and 5.1% and 12.3% for plantar flexion at 30 degrees/sec and 60 degrees/sec, respectively. No interindividual differences between 3 investigators were found. A rest interval between trials resulted in an increased plantar flexion peak torque (P < .05). Displacement of 1.5cm of the axis of rotation resulted in a change of the peak torque of 8.3% for plantar flexion (P < .01). CONCLUSIONS: A well-defined test protocol for isokinetic motor performance of the ankle dorsal and plantar flexors provides a reliable procedure for quantification of motor function in healthy subjects and in patients with HMSN1.

Adult↗

Factors affecting the variability of the torque curves at isokinetic trunk strength testing.

OBJECTIVES: To evaluate the relation between variability of the torque curves and factors such as age, gender, measurement speeds, and period from low back pain (LBP) onset at isokinetic trunk strength testing. DESIGN: Observational. SETTING: Hospital. PATIENTS: One hundred forty-three consecutive LBP patients (acute, subacute, and chronic) who received physical therapy, and 200 healthy volunteer subjects. MAIN OUTCOME MEASURES: The variability of the torque curves is an indicator of consistency of effort, and was measured as the coefficient of variance (CV) at different measurement speeds in isokinetic trunk flexion/extension strength testing. RESULTS: The CV was lower in men than in women at the faster measurement speed. LBP patients had higher CV values than healthy subjects. The CV was different according to gender and measurement speed, but not different according to age and periods from LBP onset. CONCLUSION: The CV was affected by measurement speed and gender, but not by age or period from LBP onset. Because the CV was higher in LBP patients than in healthy subjects, this value may be usable as an adjunctive index of LBP.

Abdomen↗

Osteoarthritis of the knee: isokinetic quadriceps exercise versus an educational intervention.

OBJECTIVE: To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis. DESIGN: A randomized, comparative clinical trial, with interventions lasting 8 weeks and evaluations of 12 weeks. SETTING: An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital. PATIENTS: One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee; 98 completed the entire assigned treatment. INTERVENTION: Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussions and lectures led by health care professionals. MAIN OUTCOME MEASURES: Variables studied for change were isokinetic and isometric quadriceps strength, pain and function determined by categorical and visual analog scales, and overall status using physician and patient global evaluations by the Arthritis Impact Scale, version 2, Western Ontario McMaster's Arthritis Index, and Medical Outcome Study Short Form 36. RESULTS: Both treatment groups showed significant strength gains (p < .05), which occurred over a wider velocity spectrum for the exercise group. Exercised patients also had improved pain scores for more of the variables measured than those receiving education. Both groups had positive functional outcomes and slightly improved measures of overall status. CONCLUSIONS: Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis, but a much less costly education program also showed some benefits.

Activities of Daily Living↗

Temperature dependence of the inhibitory effects of orthovanadate on shortening velocity in fast skeletal muscle.

We have investigated the effects of the orthophosphate (P(i)) analog orthovanadate (Vi) on maximum shortening velocity (Vmax) in activated, chemically skinned, vertebrate skeletal muscle fibers. Using new "temperature-jump" protocols, reproducible data can be obtained from activated fibers at high temperatures, and we have examined the effect of increased [Vi] on Vmax for temperatures in the range 5-30 degrees C. We find that for temperatures < or = 20 degrees C, increasing [Vi] inhibits Vmax; for temperatures > or = 25 degrees C, increasing [Vi] does not inhibit Vmax. Attached cross-bridges bound to Vi are thought to be an analog of the weakly bound actin-myosin.ADP-P(i) state. The data suggest that the weakly bound Vi state can inhibit velocity at low temperature, but not at high temperature, with the transition occurring over a narrow temperature range of < 5 degrees C. This suggests a highly cooperative interaction. The data also define a Q10 for Vmax of 2.1 for chemically skinned rabbit psoas fibers over the temperature range of 5-30 degrees C.

Actins↗

Stretch activation and nonlinear elasticity of muscle cross-bridges.

When active insect fibrillar flight muscle is stretched, its ATPase rate increases and it develops "negative viscosity," which allows it to perform oscillatory work. We use a six-state model for the cross-bridge cycle to show that such "stretch activation" may arise naturally as a nonlinear property of a cross-bridge interacting with a single attachment site on a thin filament. Attachment is treated as a thermally activated process in which elastic energy must be supplied to stretch or compress the cross-bridge spring. We find that stretch activation occurs at filament displacements where, before the power stroke, the spring is initially in compression rather than in tension. In that case, pulling the filaments relieves the initial compression and reduces the elastic energy required for attachment. The result is that the attachment rate is enhanced by stretching. The model also displays the "delayed tension" effect observed in length-step experiments. When the muscle is stretched suddenly, the power stroke responds very quickly, but there is a time lag before dissociation at the end of the cycle catches up with the increased attachment rate. This lag is responsible for the delayed tension and hence also for the negative viscosity.

Adenosine Triphosphate↗

Friction between human finger flexor tendons and pulleys at high loads.

A method was developed to indirectly measure friction between the flexor tendons and pulleys of the middle and ring finger in vivo. An isokinetic movement device to determine maximum force of wrist flexion, interphalangeal joint flexion (rolling in and out) and isolated proximal interphalangeal (PIP) joint flexion was built. Eccentric and concentric maximum force of these three different movements where gliding of the flexor tendon sheath was involved differently (least in wrist flexion) was measured and compared. Fifty-one hands in 26 male subjects were evaluated. The greatest difference between eccentric and concentric maximum force (29.9%) was found in flexion of the PIP joint. Differences in the rolling in and out movement (26.8%) and in wrist flexion (14.5%) were significantly smaller. The force of friction between flexor tendons and pulleys can be determined by the greater difference between eccentric and concentric maximum force provided by the same muscles in overcoming an external force during flexion of the interphalangeal joints and suggests the presence of a non-muscular force, such as friction. It constitutes of 9% of the eccentric flexion force in the PIP joint and therefore questions the low friction hypothesis at high loads.

Adolescent↗

Interaction of the movement-dependent, extrafusal and fusimotor after-effects in the firing of the primary spindle endings.

The after-effects of the firing of the primary spindle endings were studied in ankle extensor muscles of cats under Nembutal anesthesia. The activities of 27 primary endings of the muscle spindles from mm. soleus, plantaris, and gastrocnemius have been analysed in various combinations of fusimotor and extrafusal stimulation and application of the mechanostimulation to the spindle bearing muscle. Short-term simulation of static gamma-axons evoked a post-stimulation increase in the spindle ending firing, which can be recorded under both isometric and isotonic conditions on applying a weak extrafusal stimulation or without it. The movement-dependent after-effects were tested with a double-trapezoid pattern of muscle length (or load) changes. The after-effects consisted of the difference of firing rates at the same values of muscle length (or load) with opposite direction of movement to the steady states; these uncertainties were also present during constant stimulation of static gamma-axons. The rate difference showed a tendency to a certain decrease with stimulation rate increment. For diapason of the stimulation rates up to 125 impulses/s a small negative correlation (r = -0.61) between the firing rate differences and the gamma-stimulation rate has been registered in the population of primary endings tested under length servo-control conditions. Using a frequency-modulated intrafusal stimulation, a clockwise hysteresis dependence of the spindle firing rate upon stimulation rate was demonstrated. The pronounced after-effects were shown to exist for steady rates of stimulation: the discharge rates were always higher after stimulation rate increase and lower after its decrease. Fusimotor after-effects were effectively destroyed by both the extrafusal stimulation and the cyclic length (load) changes evoked lengthening-shortening movements of the muscle. The results obtained can be considered as evidence for a hypothesis that history-dependent behavior of muscle spindles is mainly connected with hysteresis of the intrafusal muscle fibers and the whole spindle bearing muscle.

Animals↗

A method of measuring finger force with the Kin-Com dynamometer.

The purpose of this study was to determine whether the force of a finger could be measured with a new system based on an attachment to the Kin-Com dynamometer, and to define the reproducibility of the finger force measurement. Eleven male subjects (age, 27.6 +/- 6.12 years) took part. All were free of orthopedic problems in the tested hand. Mean forces of the index and little finger for concentric and eccentric motion were measured using the new system. Overall coefficients of variation (OCVs) were calculated as an index of reproducibility. The reproducibility of force curves was considered good when an OCV was less than 20%. The OCVs for mean force of the index finger and for eccentric motion of the little finger were less than the 20% standard, at 10.7 and 14.0, respectively. The OCV for concentric motion of the little finger was greater than 20%. The findings suggest that measurement of finger force is feasible with the new Kin-Com attachment.

Adult↗

The neuromuscular reaction to continuous dynamic jaw extension in cases with restricted mouth opening.

20 patients with severe trismus resulting from either trauma or infection have been treated using the method of "continuous dynamic jaw extension". The clinical results and the electromyographic tests show that almost complete rehabilitation of mandibular movement is possible. The treatment is most effective during the healing phase of the abscess and as an early treatment for the traumatised patient. Extension exercises should not be undertaken during the exudative phase of abscess formation. The reaction ability of the masticatory musculature obtained from the electromyographic investigations is defined in the "reactive myotonus-index". Thus the jaw extension appliance used is helpful both in the diagnosis and treatment of severe trismus.

Abscess↗

Reciprocal coactivation patterns of the medial and lateral quadriceps and hamstrings during slow, medium and high speed isokinetic movements.

The effect of movement velocity and fatigue on the reciprocal coactivation of the quadriceps and hamstrings was investigated through analysis of the root mean square (RMS) and the median frequency (MDF) of surface electromyography for the vastus medialis (VM), vastus lateralis (VL), medial hamstrings (MH) and biceps femoris (BF). Fourteen subjects performed six continuous isokinetic knee extension and flexion movements at 60 degrees, 180 degrees and 300 degrees s(-1), and 30 continuous movements at 300 degrees s(-1) to examine muscular fatigue patterns. Statistical analyses revealed that the RMS activity of the VM displayed greater coactivation than the VL (P<0.01) and the BF displayed greater coactivation than the MH (P<0.0001). There was no effect of velocity on the coactivation levels of the VM, the VL, or the MH; however, there was an effect of velocity on the coactivation levels of the BF (P<0.0001). Relative to MDF activity, the MH shifted upward as velocity increased (P<0. 01) while the BF decreased between 180 and 300 degrees s(-1) (P<0. 01). Results of the muscular fatigue test indicated that the RMS activity of the VM showed a higher degree of coactivation than the VL (P<0.01) and the BF showed approximately three times the coactivation level of the MH (P<0.001). The MDF of the VL and MH shifted downward as the repetitions progressed (P<0.01) with no changes for the VM or for the BF. Results of this study suggest that during isokinetic testing, both the VM and BF have significantly greater reciprocal coactivation levels when compared to the VL and MH, respectively. In addition, these results suggest that motor unit recruitment patterns of the VM and VL and the MH and BF differ with regard to the effects of velocity and fatigue.

Adult↗