Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to one year.

Our understanding of the effects of long-term denervation on skeletal muscle is heavily influenced by an extensive literature based on the rat. We have studied physiological and morphological changes in an alternative model, the rabbit. In adult rabbits, tibialis anterior muscles were denervated unilaterally by selective section of motor branches of the common peroneal nerve and examined after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area by 50-60% and tetanic force by 75%, with no apparent reduction in specific force (force per cross-sectional area of muscle fibers). The loss of mass was associated with atrophy of fast fibers and an increase in fibrous and adipose connective tissue; the diameter of slow fibers was preserved. Within fibers, electron microscopy revealed signs of ultrastructural disorganization of sarcomeres and tubular systems. This, rather than the observed transformation of fiber type from IIx to IIa, was probably responsible for the slow contractile speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no significant differences. At no stage was there any evidence of necrosis or regeneration, and the total number of fibers remained constant. These changes are in marked contrast to the necrotic degeneration and progressive decline in mass and force that have previously been found in long-term denervated rat muscles. The rabbit may be a better choice for a model of the effects of denervation in humans, at least up to 1 yr after lesion.

Implantable device for long-term electrical stimulation of denervated muscles in rabbits.

Although denervating injuries produce severe atrophic changes in mammalian skeletal muscle, a degree of functional restoration can be achieved through an intensive regime of electrical stimulation. An implantable stimulator was developed so that the long-term effects of different stimulation protocols could be compared in rabbits. The device, which is powered by two lithium thionyl chloride batteries, is small enough to be implanted in the peritoneal cavity. All stimulation parameters can be specified over a wide range, with a high degree of resolution; in addition, up to 16 periods of training (10-180 min) and rest (1-42 h) can be set in advance. The microcontroller-based device is programmed through a bidirectional radiofrequency link. Settings are entered via a user-friendly computer interface and annotated to create an individual study protocol for each animal. The stimulator has been reliable and stable in use. Proven technology and rigorous quality control has enabled 55 units to be implanted to date, for periods of up to 36 weeks, with only two device failures (at 15 and 29 weeks). Changes in the excitability of denervated skeletal muscles could be followed within individual animals. Chronaxie increased from 3.24 +/- 0.54 ms to 15.57 +/- 0.85 ms (n = 55, p < 0.0001) per phase in the 2 weeks following denervation.

Kinematic evaluation in Parkinson's disease using a hand-held position transducer and computerized signal analysis.

BACKGROUND: The objective of this work was to develop a device for quantification of akinesia in Parkinson's disease, for the use in home monitoring of PD patients, as a part of home telecare programs. For this purpose a simple movement task is to be preferred, and the measurement devices must be small, lightweight, and easy to use, so patients may perform the measurements unattended. Another intended application was optimisation of the electrode position during implantations of neuromodulation systems for treatment of Parkinson. METHOD: A hand held transducer was used to measure the position of the thumb while the patient repeatedly flexed and extended the thumb. The position data was sampled and stored on a personal computer with a plug in converter card and software. Measurements were performed on 15 PD patients and 6 age-matched controls. Signal analysis procedures were developed in order to automatically derive numerical parameters that quantify the movement performance. In order to select the most relevant parameters, they were correlated to Unified Parkinson Disease Rating Scale (UPDRS) motor scores (Spearman's rank, single sided, p < 0.05). FINDINGS: In reviews of the raw position signals the amplitude and frequency was found to be lower in patients than in controls. In patients the movement was frequently interrupted by short periods of hesitation. The calculated parameters of covered distance (correlation coefficient r = -0.63), hesitation (r = 0.64) and frequency (r = -0.6) were found to be most relevant, as they correlated best to the UPDRS hand pronation/supination score. DISCUSSION: The equipment proved to be fast to setup and easy to use. The signal analysis methods provided meaningful numerical parameters for quantification of akinesia, represented in hand pronation/supination. These results suggest that the described methods may be useful for telemedicine and intraoperative use.

Functional and biological test of a 20 channel implantable stimulator in sheep in view of functional electrical stimulation walking for spinal cord injured persons.

A newly developed implantable stimulator with 20 output channels, mainly intended for the stimulation of lower extremities in paraplegics, was implanted in 6 sheep over a time period of 26 weeks. Five epineural electrodes each were used to contact various nerves at different locations to elicit hip and knee extension and flexion and to make carrousel and selective stimulation possible. Different electrode application strategies in view of paraplegic standing and walking were investigated. Additional implanted electrodes allowed M-wave monitoring for selectivity investigations in 3 sheep. Stimulator, electrode leads, and electrodes proved to be reliable. Selective stimulation with electrodes placed on the trunk of the sciatic nerve could be demonstrated but with bad reproducibility. Histological investigation of the tissues surrounding electrodes and leads showed the expected stable foreign body response. Strong hip and knee extension could be gained in all cases while only weak flexion forces could be elicited in most cases. Muscle biopsies showed that daily stimulation for 8 h at threshold level caused an increase in muscle Type I fibers and a decrease in Type IIc fibers. Implants and electrodes fulfill the most important functional and biological criteria for their clinical application for paraplegic walking. The intention to provide selective flexion functions via epineural stimulation could not be demonstrated sufficiently in this animal model.

Basic design and construction of the Vienna FES implants: existing solutions and prospects for new generations of implants.

We can distinguish 3 generations of FES implants for activation of neural structures: 1. RF-powered implants with antenna displacement dependent stimulation amplitude; 2. RF-powered implants with stabilised stimulation amplitude; and 3. battery powered implants. In Vienna an 8-channel version of the second generation type has been applied clinically to mobilisation of paraplegics and phrenic pacing. A 20-channel implant of the second generation type for mobilisation of paraplegics and an 8-channel implant of the third generation type for cardiac assist have been tested in animal studies. A device of completely new design for direct stimulation of denervated muscles is being tested in animal studies. There is a limited choice of technologically suitable biocompatible and bioresistant materials for implants. The physical design has to be anatomically shaped without corners or edges. Electrical conductors carrying direct current (D.C.) have to be placed inside a hermetic metal case. The established sealing materials, silicone rubber and epoxy resin, do not provide hermeticity and should only embed DC-free components. For electrical connections outside the hermetic metal case welding is preferable to soldering; conductive adhesives should be avoided. It is advisable to use a hydrophobic oxide ceramic core for telemetry antenna coils embedded in sealing polymer. Cleaning of all components before sealing in resin is of the utmost importance as well as avoidance of rapid temperature changes during the curing process.

[EMG monitoring in functional electrostimulation]. / EMG-Monitoring bei funktioneller Elektrostimulation.

When using functional electrical stimulation (FES), correct adjustment of stimulation parameters, and monitoring of the stimulated muscle is mandatory if tissue damage is to be avoided. Although several FES systems are already in regular use, a method for direct muscle monitoring is still lacking. This paper investigates the suitability of the electromyogram (EMG) for such a purpose. In six sheep, the right latissimus dorsi muscle (LDM) and the associated thoracodorsal nerve were exposed. Stimulation was effected via electrodes placed on the nerve. Three electrodes were placed in the LDM for EMG recording, and the tendon was connected to a force transducer for isometric force measurement. Stimulation was applied for one second (burst), followed by a three-second pause. The stimulation current was increased in 0.2 mA steps, starting at 0 mA and ending at 4 mA. Throughout the investigation, the EMG signal was monitored with an oscilloscope. In addition, the EMG signal and the force transducer signal were recorded for subsequent analysis. An analysis of the data of all six sheep revealed an almost linear relationship between muscle force and m-wave amplitude (magnitude of r = 0.95, p < 0.001). M-wave monitoring during EMG recording with three intramuscular electrodes is a reliable method of monitoring FES-induced muscle activity, but the absolute force cannot be measured.

Preparation of a skeletal muscle ventricle in sheep: severe damage to the Latissimus dorsi muscle due to mobilization before preconditioning.

As part of a study examining the use of a skeletal muscle ventricle for cardiac assistance in sheep, a new concept of muscle preconditioning was put into practice. We aimed to produce a latissimus dorsi muscle (LDM) capable of performing chronic work immediately after the construction of a skeletal muscle ventricle. The left LDM was detached from the thoracic wall, divided longitudinally and reattached in situ to achieve vascular delay. The right LDM was left unaffected. Thereafter, preconditioning of both LDM was started according to the clinically approved stimulation protocol for cardiomyoplasty. Preconditioning of the unaffected right LDM in situ resulted in a complete muscle fiber transformation with no signs of degeneration or necrosis. Mobilization of the left LDM before preconditioning led to a distinct damage of the muscle. During conditioning, the increase in burst duration from 2 to 3 impulses in sheep A and from 3 to 5 impulses in sheep B resulted in a homogenous degeneration of the muscle fibers of the left LDM. Histomorphological analysis showed a dramatic increase in the percent perimysial and endomysial connective tissue. The applied concept of muscle prefabrication proved to be a failure. Muscle splitting and mobilization followed by vascular delay and in situ conditioning as a concept of muscle prefabrication should be strictly avoided.

Long-term electromyogram recording from the posterior cricoarytenoid muscle as a potential biological trigger for phrenic pacing: results of an animal study.

Diaphragm pacing has been used to restore respiration in approximately 1,000 patients worldwide suffering from high quadriplegia or from central alveolar hypoventilation syndrome. Compared with conventional mechanical ventilation, electrophrenic respiration (EPR) reduces the risk of pulmonary infections and increases the mobility of patients. Voluntary activation of the pacemaker during speech would improve patients' quality of life and allow application of EPR in a more physiological way. An animal study was performed to investigate the electromyogram (EMG) of the posterior cricoarytenoid (PCA) muscle and the movement of the glottis via impedance measurement (electroglottography) with the aim to examine reproducibility and stability of the recordings from the PCA muscle as a potential biological trigger for a phrenic pacemaker. The EMG of the PCA muscle was recorded via implanted electrodes for a 200 day period. The EMG signal proved stable for that period, artifacts caused by movements can be suppressed, and swallowing can be detected. In contrast, impedance measurement to detect movement of the glottis proved not useful. Based on the results of this study, the use of the PCA EMG as a biological trigger for a phrenic pacemaker has to be considered a realistic option.

Battery-powered miniature implant for electrical nerve stimulation.

The range of application of implantable stimulators in functional electrical stimulation (FES) for therapeutic purposes and for the restoration of lost or damaged functions has steadily grown within the last 20 years. Each time a clinically used method is improved, a new field of FES application explored or basic research conducted, animal experiments are needed to check and evaluate the findings and results. It is precisely for this use that the stimulation system described in this paper was developed. The battery-powered single-channel stimulator can be used for the excitation of motor and sensory nerves with monophasic or biphasic impulses. All parameters and functions are programmable via the bidirectional telemetry circuit. Implant programming is achieved by a laptop computer, supported by a graphical user interface, instead of by a specially designed programmer. The maximum settings of the stimulation parameters are: frequency 100 Hz, monophasic pulse duration 0.8 ms, biphasic pulse duration 1.6 ms, stimulation current 3 mA. The implant volume was reduced to 2 cm3 (length 23 mm, width 13 mm, height 7.5 mm), lowering the weight to 3.6 g. Due to this small volume the implant can be used in small animals. The power supply via battery obviates the need for transcutaneous tunneling or permanent external high-frequency senders and facilitates the keeping of the animals.

Battery-powered implantable nerve stimulator for chronic activation of two skeletal muscles using multichannel techniques.

Chronic activation of skeletal muscle is used clinically in representative numbers for diaphragm pacing to restore breathing and for dynamic graciloplasty to achieve fecal continence. The 3 different stimulation techniques currently used for electrophrenic respiration (EPR) all apply high frequency powered implants. It was our goal to make these stimulation methods applicable for EPR by a battery-powered nerve stimulator that would maximize the patient's freedom of movement. Additionally, the system should allow the implementation of multichannel techniques and alternating stimulation of 2 skeletal muscles as a further improvement in graciloplasty. Generally, the developed implantable nerve stimulator can be used for simultaneous and alternating activation of 2 skeletal muscles. Stimulation of the motor nerve is achieved by either single channel or multichannel methods. Carousel stimulation and sequential stimulation can be used for graciloplasty as well as for EPR. For EPR we calculated an operating time of the implant battery of 4.1 years based on the clinically used stimulation parameters with carousel stimulation. The multichannel pulse generator is hermetically sealed in a titanium case sized 65 x 17 mm (diameter x height) and weighs 88 g.

Personal computer supported eight channel surface stimulator for paraplegic walking: first results.

Today functional electrical stimulation (FES) is used among other treatments to restore hand and arm function, to restore mobility of the lower extremities, for phrenic pacing, and in cardiomyoplasty. Common to all FES applications is that they require careful setup of stimulation parameters. To improve these tasks, personal computer (PC) based software for stimulation parameter evaluation and data acquisition was written. First, the described software was used to mobilize paraplegic patients in conjunction with an 12C bus controlled 8 channel surface stimulator. Electrodes were placed on each leg on the m. quadriceps and m. gluteus for hip and knee extension and the peroneal nerve to elicit flexion reflex. The fourth channel was used to correspond to subjects' individual needs. The stimulation patterns for standing up, walking, and sitting down easily could be set up and optimized by adjusting up to 128 stimulation parameters in a task-specific way.

MYOSTIM-FES to prevent muscle atrophy in microgravity and bed rest: preliminary report.

Long-term flights in microgravity cause atrophy and morphological changes of skeletal muscles. Training with mechanical devices is insufficient regarding the required time to exercise and space for devices. The objective of this project is to develop a passive training method based on functional electrostimulation (FES) to preserve muscle mass and fiber composition with minimal impairment to the cosmonaut. For a pilot experiment on the MIR space station, a suitable 8 channel FES device was developed. It consists of electrode trousers that carry surface electrodes and cables, 2 interconnected 4 channel stimulators, and a laptop personal computer (PC) for stimulator programming and processing compliance data. An automatic extensive training of 4 muscle groups of the lower extremities is performed for 6 h/day, with 1 s on and 2 s off tetanic contractions at 20-30% of maximum tetanic muscle force. The synchronous activation of antagonists of the thigh and lower leg prevents uncoordinated movements.

Dynamic force responses in electrically stimulated triceps surae muscles: effects of fatigue and temperature.

To elicit dynamic force responses (unfused tetani) in isometric triceps surae muscles, low frequency electrical stimulation ranging from 12.5 to 30.0 Hz was applied. The fusing frequency (FF) and the relative dynamic force amplitude (DF) at the 20% and 40% maximum voluntary contraction (MVC) levels were calculated as parameters to determine effects of muscle fatigue (n = 6) and local muscle cooling. In the fatigued muscle (15 min plantar flexion at a 20% MVC level), the FF and DF increased when the fatigue was induced by voluntary contraction (FF increased from 19.6 to 22.5 Hz at 20% MVC) and also when induced by electrical stimulation (FF increased from 19.2 to 23.3 Hz). Cooling of the muscles showed an inverse effect on both parameters, indicating contractile slowing. The responsible physiological mechanisms as well as practical applications, using low frequency stimulation to monitor degenerative changes in muscles, are discussed.

[Modular PC-based data acquisition and processing system for biological signals]. / Modulares PC-unterstütztes Messwerterfassungs- und Datenverarbeitungssystem für biologische Signale.

The data acquisition system described here is designed for biomedical research and permits the recording of up to eight biological signals simultaneously. A personal computer using the Windows 95 operating system is employed for data monitoring, data processing and analysis during experiments. The system has been designed for reliability, economy, flexibility and ease of handling, with the aim of achieving universal application. To avoid interface incompatibility, problems with transfer protocols and the data formats of commercially available products, analog signals are used for further processing. The individual input channels are electrically isolated from one another and the PC to avoid ground loops, and for reasons of safety. An isolated voltage supply is available for pre-amplifiers and bridges. A bandwidth of 0-5 kHz and the maximum sampling rate of 12.5 kHz suffice to pick up higher frequency signals such as EMG and ENG. The modular software and hardware concepts permit the use of almost any desktop or laptop PC as a central processing unit. The PC handless documentation, data acquisition, data analysis and the preparation of publications. If needed, further analytical functions can be added in modular form. Finally, the option of saving data in the ASCII format permits processing of results with such standard software packages as Excel, Access, Matlab and Origin.

Multifunctional implantable nerve stimulator for cardiac assistance by skeletal muscle.

Different methods are used, clinically and experimentally, to assist severely impaired heart function by means of skeletal muscle. The efficiency of these methods is restricted by skeletal muscle losing strength after transpositioning and during conditioning and not being sufficiently resistant to fatigue. This is mainly due to the nonphysiological activation of the nerves by electrical stimulation. We have developed a battery operated, ECG triggered multichannel implant that is capable of implementing various advanced stimulation techniques. The stimulator can activate 2 skeletal muscles via the motor nerves. It allows for application of multichannel stimulation methods, i.e., carousel stimulation and sequential stimulation, as well as the programming of optimized pulse trains. Synchronization delay and burst duration can be automatically and dynamically adapted to the heart rate. The multichannel stimulator is hermetically sealed in a titanium case. Its calculated life span on the basis of the integrated battery is 3-5 years, depending on the programmed stimulation parameters. The implant dimensions are 65 x 17 mm (diameter x height), and it weighs 93 g. The implant has been tested in vitro as well as in vivo.

Experimental development of an electrically stimulated biological skeletal muscle ventricle for chronic aortic counterpulsation.

OBJECTIVE: The chronic shortage of donor organs for cardiac transplantation and the high costs for mechanical assist devices demand the development of alternative cardiac assist devices for the treatment of severe heart failure. Cardiac assistance by stimulated skeletal muscles is currently investigated as such a possible alternative. The goal of the presented study was to construct a newly designed biological skeletal muscle ventricle and to evaluate its possible hemodynamic efficacy in an acute sheep model. METHODS: A total of 14 adult sheep were used for acute experiments. The entire thoracic aorta including the aortic root was excised from a donor sheep. An aorto-pericardial pouch conduit (APPC) was created by enlarging the aortic circumference in its middle section with two strips of pericardium. This biological conduit was anastomosed in parallel to the descending aorta of a recipient sheep, using the aortic root as an inflow valve to the conduit. Stimulation electrodes were applicated to the thoracodorsal nerve and the latissimus dorsi muscle was detached from the trunk and wrapped around the pouch. ECG-triggered functional electrical stimulation was applied during cardiac diastole to simulate aortic counterpulsation. Stimulation was performed during various hemodynamic conditions. RESULTS: A standardised surgical procedure suitable for long term studies was established during six experiments. An APPC, with 70-80 mm filling volume, was found to be of optimal size. In another eight experiments, hemodynamic measurements were performed. Under stable hemodynamic conditions the stimulation of the biological skeletal muscle ventricle induced a significant increase of mean arterial pressure by 14% and mean diastolic pressure by 26%. During pharmacologically induced periods of cardiac failure, the stimulation of the APPC increased mean arterial pressure by 13% and mean diastolic pressure by 19%. In all eight experiments, the diastolic peak pressure reached supra-systolic values during stimulation. CONCLUSIONS: The results demonstrate the hemodynamic efficacy of this newly designed biological skeletal muscle ventricle as an aortic counterpulsation device. Chronic experiments using a preconditioned fatigue-resistant muscle will further help to evaluate its possible clinical significance.

Useful applications and limits of battery powered implants in functional electrical stimulations.

Battery powered stimulation implants have been well-known for a long time as heart pacemakers. In the last few years, fully implantable stimulators have been used in the field of functional electrical stimulation (FES) for applications like dynamic cardiomyoplasty and electro-stimulated graciloplasty for fecal incontinence. The error rate of battery powered implants is significantly smaller than that for conventional stimulator systems, and the quality of life for the patients is increased because the need for an external power and control unit is eliminated. The use of battery powered implants is limited by the complexity of the stimulation control strategies and the battery capacity. Therefore, applications like the stimulation of lower extremities for walking, cochlea stimulation, or direct muscle stimulation cannot be supported. The improvement of implantable batteries, microcontrollers, and ultralow power products is ongoing. In the future, battery powered implants will also meet the requirements of complex applications. Systems for restoration of hand and breathing functions after spinal cord injury can be the next field of use for battery powered implants. For these purposes, we developed a battery powered multichannel implant with a sufficient life span for phrenic pacing. The problems during development and the limits of this system are described in this paper.

Computer aided adjustment of the phrenic pacemaker: automatic functions, documentation, and quality control.

Electrical stimulation of the phrenic nerves of patients with complete ventilatory insufficiency with the Vienna respiratory pacemaker has been in clinical use since 1983. During the adjustment of stimulation parameters with this device, the following problems have occurred: for some measurements like the recruitment curve, series of complete inspiration cycles have to be stimulated, which causes the danger of muscle fatigue for unconditioned patients. The documentation is completed predominantly by hand, taking time and increasing the possibility of error. As a first step to solve these problems, we developed a new stimulation and measurement system. It consists of a PC with data acquisition hardware, the necessary sensors, and amplifier circuitry. The implanted stimulator is controlled via the parallel interface. The new system offers some advantages: computer control shortens the time for measurement and documentation, and the stress on the patient and the risk of error is reduced; synchronized measurement makes it possible to use single stimulation pulses instead of bursts and ramps to reduce diaphragm fatigue; digital signal processing improves measurement results and reproducibility; and help functions and self tests are provided, together with a graphical user interface. We used sensors for air flow, diaphragm EMG, and acceleration, on up to 8 channels simultaneously. Combined sample rates of up to 100 kS/s were possible. The system could be adapted for other uses involving functional electrical stimulation with our implantable nerve stimulators. Using this equipment saves a lot of effort, and the adjustment process can be focused on improved stimulation results and better performance for the patient. Current research is studying implementation of automatic functions like acquisition of stimulation thresholds. This could result in a predominantly automated adjustment of the phrenic pacemaker and even in a closed-loop controlled system in the future.

Vienna phrenic pacemaker--experience with diaphragm pacing in children.

Eight children, five boys and three girls, aging from 2 to 13 years (M = 9 +/- 3) were treated with the "Vienna phrenic pacemaker". Indication for implantation was central alveolar hypoventilation syndrome (CAH) in one case and total ventilatory insufficiency due to high cervical cord or brain stem lesion (SCI) in seven cases. Four electrodes were applied to each phrenic nerve via sternotomy. Both hemidiaphragms were paced synchronously with increasing duty cycles to condition the diaphragms for continuous electrophrenic respiration (EPR). EPR could be performed successfully in all children but one. Four children could achieve chronical EPR, one is in conditioning period. Two patients could not be discharged from hospital due to parental neglect and died after two and three years of intermittent stimulation. Six children could be discharged from hospital, two of them died after one and four years of chronic pacing. In one case tracheotomy could be closed definitively. Ventilatory insufficiency due to CAH and SCI can be treated even in children with diaphragm pacing, provided the indication for implantation, containing medical and social aspects, was made correctly. Diaphragm pacing probably will not lengthen life of severely injured children but it can increase the quality of their life and therefore should be preferred to positive pressure mechanical ventilation.