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.

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.

Multichannel stimulation of phrenic nerves by epineural electrodes. Clinical experience and future developments.

Between 1983 and 1992, 23 patients with complete ventilatory insufficiency of differing etiologies were treated with an eight channel implant (Medimplant Inc., Vienna) for fatigue free stimulation of both phrenic nerves. Data for 15 patients with high spinal cord lesions (ages: 9-51 years) are summarized: 1) level of lesion: C0, 3 patients; C1/C2, 4; C2/C3, 8; 2) time between incident and implantation: 3-14 months; 3) diaphragm training: 1-22 months; 4) chronic pacing: 5-83 months; 5) tracheostomy closed: 7 patients; 6) living permanently at home: 13 patients; 7) respiratory rate per minute: 12-17; 8) duration of inspiration: 1.0-1.3 sec; 9) tidal volume: 7-20 ml/kg body weight; 10) volume per minute: 121-198 ml/kg body weight; 11) pH: 7.39-7.42; 12) pCO2: 22.9-38.6 mmHg; 13) pO2: 81.2-104.5 mmHg; and 14) died by December 1992, 4 patients. All currently available implants for phrenic pacing need an external power supply and radio control. The authors have developed and tested the first fully implantable device. Features of this implant include an electronic circuit based on the microcontroller MC68HC705C8; surface mounted technology (SMD); eight channels; constant current source adjustable to 5 mA in 256 steps, impulse duration: 100-1000 musec, stimulation frequency: 1-33 Hz; and minimum lifetime: 3 years. The implant is programmed via bidirectional radio transmission using an IBM compatible computer. The dimensions, including battery, eight electrode connectors, and antenna, are 67 x 48 x 13 mm. The implant weights 58 g. This new device may improve patients' safety and quality of life in the near future.

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.

Monitoring of FES-induced muscle activity by continuous EMG-recording.

Functional Electrical Stimulation (FES) requires information on the stimulated muscle for adjustment of the stimulation current, avoidance of muscle fatigue during the conditioning period and long term follow-up. Several applications of chronical FES are in clinical practice, but a system for direct registration of muscle activity under FES still does not exist. In six sheep the right Latissimus Dorsi Muscle (LDM) and Thoracodorsal Nerve were exposed. Stimulation electrodes were applied to each nerve and 3 EMG-applied sensing electrodes were placed into each LDM. The LDM tendon was connected to a force transducer. Burst stimulation was applied and the amplitude was increased from 0 to 4 mA in steps from burst to burst. EMG (M-wave) was amplified and recorded continuously via modified instrumentation amplifier, oscilloscope and tape recorder. Isometric muscle tension was recorded using force transducer, A/D interface and PC. Continuous EMG-recording was performed in all cases. Simultaneous recording of muscle tension and EMG revealed a close correlation (IrI=0.95, p < 0.0001) between the muscle strength and amplitude of the M-wave. Continuous recording of the EMG seems to be a reliable method for direct monitoring of the stimulated muscle. Three intramuscular electrodes can provide enough information to monitor FES induced muscle activity.

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.

[Circulatory support by an electrically stimulated muscle flap. Experimental experiences]. / Kreislaufunterstützung durch elektrisch stimulierte Muskellappen. Experimentelle Erfahrungen.

Functional electrical stimulation of the latissimus dorsi muscle flap for circulatory assistance extends the traditional concept of using this flap for reconstructive procedures into the field of cardiac surgery. It requires a transformed muscle which is able to contract for long periods of time without fatigue. Two main groups of experiments have been carried out in sheep. In six sheep the latissimus dorsi muscle (MLD) was transformed into a fatigue-resistant muscle by the means of multichannel stimulation of the supplying motor nerve. After that, stimulation of MLD at a frequency of 70 contractions per minute could be performed continuously without significant muscle fatigue. The loss of maximal force caused by the conditioning procedure was about one third of the initial force. In a second series of acute experiments the MLD was used for cardiomyoplasty. The muscle was divided into two parts which were wrapped around the heart in two different forms. The resting tension of the muscle was preserved. EKG-synchronous stimulation resulted in an increase in left ventricular pressure between 12 and 53%. The increase in arterial pressure was between 10,6 and 58%.

[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.

[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.

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.

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.

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.

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.

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.

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.

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.