Patient preferences for next generation neural prostheses to restore bladder function.

STUDY DESIGN: A survey administered to 66 individuals with spinal cord injury (SCI) implementing a choice-based conjoint (CBC) analysis. Six attributes with three levels each were defined and used to generate choice sets with treatment scenarios. Patients were asked to choose the scenario that they preferred most. OBJECTIVES: To determine the utility weights for treatment characteristics as well as the overall preference for the three types of neural prostheses (NP), that is Brindley, rhizotomy-free Brindley, and pudendal nerve stimulation. Earlier studies have revealed the importance of restoration of bladder function, but no studies have been performed to determine the importance of NP features. SETTING: Two academic affiliated medical systems' SCI outpatient and inpatient rehabilitation programs, Cleveland, OH. METHODS: CBC analysis followed by multinomial logit modeling. Individual part-worth utilities were estimated using hierarchical Bayes. RESULTS: Side effects had the greatest significant impact on subject choices, followed by the effectiveness on continence and voiding. NPs with rhizotomy-free sacral root stimulation were preferred (45% first choice) over pudendal afferent nerve stimulation (39% second choice) and sacral root stimulation with rhizotomy (53% third choice). Almost 20% did not want to have an NP at all times. CONCLUSION: CBC has shown to be a valuable tool to support design choices. The data showed that persons would prefer a bladder NP with minimally invasive electrodes, which would give them complete bladder function, with no side effects and that can be operated by pushing a button and they do not have to recharge themselves.

In vivo demonstration of a self-sustaining, implantable, stimulated-muscle-powered piezoelectric generator prototype.

An implantable, stimulated-muscle-powered piezoelectric active energy harvesting generator was previously designed to exploit the fact that the mechanical output power of muscle is substantially greater than the electrical power necessary to stimulate the muscle's motor nerve. We reduced to practice the concept by building a prototype generator and stimulator. We demonstrated its feasibility in vivo, using rabbit quadriceps to drive the generator. The generated power was sufficient for self-sustaining operation of the stimulator and additional harnessed power was dissipated through a load resistor. The prototype generator was developed and the power generating capabilities were tested with a mechanical muscle analog. In vivo generated power matched the mechanical muscle analog, verifying its usefulness as a test-bed for generator development. Generator output power was dependent on the muscle stimulation parameters. Simulations and in vivo testing demonstrated that for a fixed number of stimuli/minute, two stimuli applied at a high frequency generated greater power than single stimuli or tetanic contractions. Larger muscles and circuitry improvements are expected to increase available power. An implanted, self-replenishing power source has the potential to augment implanted battery or transcutaneously powered electronic medical devices.

The feline dorsal nerve of the penis arises from the deep perineal nerve and not the sensory afferent branch.

The cat has been used extensively as an animal model for urogenital studies involving the pudendal nerve. However, discrepancies persist in the literature regarding the origin of the dorsal nerve of the penis (DNP). This study used gross dissections and serial histological cross sections to demonstrate that the DNP arises from the deep perineal nerve and not the sensory afferent branch as previously reported. This finding indicates a better than previously appreciated neuroanatomical homology between the cat and human.

Design considerations for an implantable, muscle powered piezoelectric system for generating electrical power.

A totally implantable piezoelectric generator system able to harness power from electrically activated muscle would augment the power systems of implanted functional electrical stimulation devices by reducing the number of battery replacement surgeries or by allowing periods of untethered functionality. The generator design contains no moving parts and uses a portion of the generated power for system operation. A software model of the system was developed and simulations performed to predict the output power as the system parameters were varied within their constraints. Mechanical forces that mimic muscle forces were experimentally applied to a piezoelectric generator to verify the accuracy of the simulations and to explore losses due to mechanical coupling. Depending on the selection of system parameters, software simulations predict that this generator concept can generate up to 690 microW of power, which is greater than the power necessary to drive the generator, conservatively estimated to be 46 microW. These results suggest that this concept has the potential to be an implantable, self-replenishing power source and warrants further investigation.

Topography of spinal neurons active during hindlimb withdrawal reflexes in the decerebrate cat.

There exists a spatial organization of receptive fields and a modular organization of the flexion withdrawal reflex system. However, the three dimensional location and organization of interneurons interposed in flexion reflex pathways has not been systematically examined. We determined the anatomical locations of spinal neurons involved in the hindlimb flexion withdrawal reflex using expression of the immediate early gene c-fos and the corresponding FOS protein. The flexion withdrawal reflex was evoked in decerebrate cats via stimulation of the tibial or superficial peroneal nerve. Animals that received stimulation had significantly larger numbers of cells expressing FOS-like immunoreactivity (42.7+/-2.3 cells/section, mean+/-standard error of the mean) than operated unstimulated controls (18.6+/-1.4 cells/section). Compared with controls, cells expressing FOS-like immunoreactivity were located predominantly on the ipsilateral side, in laminae IV-VI, at L6 and rostral L7 segments, and between 20% and 60% of the distance from the midline to the lateral border of the ventral gray matter. Labeled neurons resulting from tibial nerve stimulation were medial to neurons labeled following superficial peroneal nerve stimulation in laminae I-VI, but not VII. The mean mediolateral positions of labeled neurons from both nerves shifted medially as the transverse plane in which they were viewed was moved from rostral to caudal and as the coronal plane in which they were viewed was moved from dorsal to ventral. The mediolateral separation between populations of labeled cells was consistent with primary afferent projections and the location of reflex encoders. This topographical segregation corresponding to different afferent inputs is a possible anatomical substrate for a modular organization of the flexion withdrawal reflex system.

Sustained skeletal muscle power for cardiac assist devices: implications of metabolic constraints.

A device to harness power from skeletal muscle contracting in a linear configuration is under development. This application requires a sustained level of power that is dependent upon muscle mechanics and metabolic properties. A biomechanical muscle model and a metabolic model constructed from experimental data were used to predict maximum power available in a sustainable region of loading and stimulation conditions. Latissimus dorsi (LD) of four goats were evaluated in vivo after a 10 week in situ conditioning protocol with an implanted Telectronics myostimulator. The LD insertion was reconnected to a hydraulic loading system, allowing isometric and isotonic contractions for biomechanical characterization. Metabolic utilization was measured by a thermister based myothermic technique. Brief fatigue tests of working isotonic contractions revealed stimulation conditions associated with sustained power. The results show metabolic utilization was dependent on contraction duration, rate, force, and stroke. The region of sustainable contractions was found for a range of durations of 0.1 to 0.6 sec and rates of 10 to 120 bpm. The boundary for the sustainable power region was well approximated by a constant value of metabolic utilization. A constant duty cycle (contraction to cycle duration ratio) also approximated the sustained power but differed by as much as 30% during the shorter contraction durations. The results demonstrate that a mechanical muscle model can predict maximum sustained power when the operating conditions are constrained to a sustainable range determined by a metabolic model. Furthermore, metabolic constraints influence the optimum conditions for sustained power needed in the design of skeletal muscle powered assist devices.

Relative metabolic utilization of in situ rabbit soleus muscle: thermistor-based measurements and model.

Electrically conditioned skeletal muscle can provide the continuous power source for cardiac assistance devices. Optimization of the available sustained power from in vivo skeletal muscle requires knowledge of its metabolic utilization and constraints. A thermistor-based technique has been developed to measure temperature changes and to provide a relative estimate for metabolic utilization of in situ rabbit soleus muscle. The relative thermistor response, active tension and muscle displacement were measured during cyclic isometric and isotonic contractions across a range of muscle tensions and contraction durations. The thermistor response demonstrated linear relationships versus both contraction duration at a fixed muscle length and active tension at a fixed contraction duration (r(2)=0.90+/-0.14 and 0.70+/-0.21, respectively; means +/- s.d.). A multiple linear regression model was developed to predict normalized thermistor response, DeltaT, across a range of conditions. Significant model variables were identified using a backward stepwise regression procedure. The relationships for the in situ muscles were qualitatively similar to those reported for mammalian in vitro muscle fiber preparations. The model had the form DeltaT=C+at(c)F+bW, where the constant C, and coefficients for the contraction duration t(c) (ms), normalized active tension F and normalized net work W were C=-1.00 (P<0.001), a=5.97 (P<0.001) and b=2.12 (P<0.001).

Evaluation of a skeletal muscle energy convertor in a chronic animal model.

A device is under development for powering cardiac assist devices with skeletal muscle contracting in a linear configuration by converting muscle work to hydraulic energy. Prototype devices are being implanted in goats to study device performance and associated muscle mechanics. Percutaneous hydraulic lines provide the means to control muscle load and evaluate muscle performance during an electrical conditioning protocol. Chronic implant durations ranged from 36 to 87 days in 7 goats. The latissimus dorsi muscle (LDM) insertion was reconnected to the device with a tendon loop. A sternal plate attached with bone screws, and a rib clamp secured the device. A new modular sternal mount design was implemented to eliminate plate loosening that complicated early implants. Extensive bone remodeling around the rib clamp was observed. The tendon attachment demonstrated sufficient initial strength; however, in five implants, efforts to repair the tendon were required. Device encapsulation was observed, but the device continued to cycle freely and no tethering adhesions to the device were found. Interactions between the capsule wall and LDM seemed to limit LDM movement in some cases. Development of a long-term animal model for energy convertor evaluations is an important step toward skeletal muscle powered cardiac assist.

Chronic implantation of a skeletal muscle energy convertor for cardiac assist devices: a preliminary report.

An efficient energy convertor capable of driving a variety of cardiac assist devices is being developed in goats. Muscle work in a linear configuration is converted to hydraulic energy and transmitted to an external test system that controls muscle loads during shortening contractions. This investigation focuses on the variation of muscle characteristics and optimal power output during muscle conditioning. The energy convertor was mounted on the rib cage, the latissimus dorsi insertion reattached to the device, and percutaneous hydraulic lines exited near the spine. Following device, stimulator, and intramuscular electrode implantation, a progressive conditioning protocol was initiated. Weekly biomechanical muscle characterization was performed in the conscious animal, with single twitch and tetanic contractions performed under isometric and isotonic conditions. The characterization data provide a measure of available power, as well as inputs, for a computer simulation that predicts optimal muscle power output and operating conditions. These ongoing implants provide insight into the available muscle power and suggest an implantable energy convertor is feasible. Development of an energy convertor is an important step toward tether free skeletal muscle powered cardiac assist. These studies will be expanded in number and duration to further investigate the effects of conditioning and identify improvements in device development.

Progressive pressure expansion in skeletal muscle ventricle conditioning.

Skeletal muscle ventricle (SMV) conditioning typically results in reduced muscle performance. This study investigated the effects of progressive SMV resting pressure expansion and dynamic muscle training on SMV pumping capability. SMVs were formed from latissimus dorsi muscle in five goats. Three experimental SMVs were conditioned against a compliant pneumatic implant system. SMV resting pressure was progressively increased as the SMV adapted to each increment. Resting pressure rose from 40 to 100-120 mmHg over an 8 week period of time. Two control SMVs were conditioned against a non expanded incompressible implant. Both experimental and control SMVs were electrically burst stimulated for at least 6 weeks after an initial 2 week vascular delay interval. Results demonstrate that 1) experimental SMVs increased in volume; 2) SMV passive and active (evoked isovolumetric pressure) pressure-volume curves adapted to the increasing or static resting volume; and 3) two of three experimental SMVs generated greater stroke volumes than control SMVs across a range of counterpulsation pressures and electrical stimulation parameters. Progressive pressure expansion using a compliant implant system improved final SMV pumping performance and merits further investigation.