Cheryl A. Hassett

PROPERTIES OF SINGLE MOTOR UNITS IN MEDIAL GASTROCNEMIUS MUSCLES OF ADULT AND OLD RATS

1. The purpose of this study was to determine the role of motor unit remodelling in the deficit that develops in the maximum isometric tetanic force (Fo) of whole medial gastrocnemius (MGN) muscles in old compared with adult rats. The Fo values and morphological data were determined for MGN muscles and eighty‐two single motor units in muscles of adult (10‐12 months) and sixty‐two units in those of old (24‐26 months) F344 rats. During an unfused tetanus, fast and slow (S) motor units were identified by the presence and absence of sag, respectively. Fast‐fatigable (FF) and fast‐fatigue‐resistant (FR) units were classified by fatigue indices less than or greater than 0.50, respectively. 2. For old rats, whole MGN muscle Fo was 29% less than the value of 11.2 N measured for adult rats. The deficit in whole muscle Fo of old rats resulted from equivalent decreases in the number of motor units, 16% smaller than the adult value of ninety‐seven, and in the mean motor unit Fo value, 14% less than the adult value of 117 mN. 3. With ageing, little motor unit remodelling occurred in FR units, whereas the S and FF motor units demonstrated dramatic, but opposing, changes. For S units, the number of units remained constant, but the number of fibres per motor unit increased 3‐fold from 57 to 165. In contrast, the number of FF units decreased by 34% and the number of fibres per motor unit of the remaining units decreased to 86% of the adult value of 333. The age‐related remodelling of motor units appeared to involve denervation of fast muscle fibres with reinnervation of denervated fibres by axonal sprouting from slow fibres.

Number of contractions to maintain mass and force of a denervated rat muscle

Within 5 weeks, denervated extensor digitorum longus (EDL) muscles of rats lose 66% of mass, 91% of force, and 76% of fiber cross‐sectional area (CSA). We previously determined the parameters of electrical stimulation for denervated rat EDL muscles to generate tetanic contractions sufficient to maintain mass and force close to control values. Using these parameters, we tested the hypothesis that a range exists for number of contractions per day, below and above which values for mass, maximum force, and fiber CSA are lower than values for innervated control muscles. For 5 weeks, denervated EDL muscles were stimulated to generate between 25 and 5000 contractions daily with contractions separated by constant intervals of rest, repeated 24 h per day. Force was not maintained with fewer than 200 or more than 800 contractions daily, whereas mass and fiber CSA were not maintained with fewer than 50 contractions daily. Protocols of stimulation that maintain muscle mass and force during prolonged periods of denervation may minimize problems clinically associated with denervation atrophy. Muscle Nerve 30: 77–86, 2004

Characterization of skeletal muscle effects associated with daptomycin in rats

Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram‐positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (≤0.22%) with loss of plasma membrane integrity and/or infiltration by neutrophils and/or macrophages. Multiple doses of daptomycin are required for a quantifiable effect on skeletal muscles of rats. Some fibers were Evans Blue Dye–positive but were not yet infiltrated by neutrophils. This suggests that the sarcolemma may be the primary target for the observed effects. Muscle Nerve, 2010

Abstract 61: Characterization of Regenerative Peripheral Nerve Device Signaling during Evoked Maximal and Submaximal Fatiguing Conditions.

PurPose: Regenerative peripheral nerve interface devices (RPNI devices) transduce signals between remaining peripheral nerves of a residual limb and motorized prostheses. RPNI devices consist of a transferred muscle neurotized by a transected peripheral nerve with electrodes secured to the muscle for RPNI signal transduction. RPNI device maximal twitch signaling has been characterized; however, device function during repetitive signaling has not been studied. Our purpose was to characterize RPNI device continuous submaximal signaling including fatigability with respect to measures of maximal signal.

Abstract 60: Signal Strength, Reliability, and Validity of Active Regenerative Peripheral Nerve Interface Device Operation during Voluntary Movement

PurPose: Regenerative Peripheral Nerve Interface (RPNI) devices successfully transduce peripheral nerve action potentials to electrical signals suitable for prosthesis control. Voltage changes are the controlling mechanism and can be observed during electromyography (EMG). However, RPNI device signaling has not been characterized during voluntary movements. This study: a) characterizes active RPNI signal strength compared to background activity and b) defines the reliability and validity of RPNI signal function during purposeful movements.

Complete regenerative peripheral nerve interfaces, fatigue and recovery

Modern technology has taken great strides to restore motion to amputees with prostheses. A key limitation in many cases is lack of a reliable controlling interface to the prosthetic devices. To address this issue, our lab has developed the Regenerative Peripheral Nerve Interface (RPNI). RPNIs transduce signals between residual peripheral nerves, muscle grafts, and prosthetic devices. Prior to this study, RPNIs signal production was primarily evaluated during single evoked maximal action potential. The purpose of this study was to characterize RPNI function during and after repeated submaximal use. RPNIs (n=5) were constructed in a rat model by transferring the EDL muscle from the lower hind limb to the hip region and implanting the transected peroneal nerve into the muscle. Control EDL muscles (n=8) were left in the native location. The muscles were evaluated at least five months postoperatively in terms of maximum evoked compound muscle action potentials, force production, force production during repeated use, and post-fatigue force production. There was a strong correlation between maximum compound muscle action potential amplitude and maximum contractile force (r=0.83 p <; 0.01); thus, force was an indication of signaling. RPNI and Control muscles both fatigued as exponential regressions. Percent post fatigue force production did not differ significantly between the groups, with Controls recovering to 85% of initial maximum force and RPNIs recovering to 60%. RPNIs produce and recover signals in the same relative manner as Controls indicating RPNIs are prime candidates as controlling interfaces for myoelectric prosthetic devices.

Abstract 49: Neuroprosthetic Hand Real-Time Proportional Control by Rodent Regenerative Peripheral Nerve Interfaces

patients experiencing DSWI requiring flap stayed significantly longer in the hospital (28.4 versus 13.3 days, p < 0.001), more often experienced subsequent unplanned readmission (46.5% versus 6.5%, p < 0.001), were more likely to experience 90-day mortality (18.2% versus 5.0%, p < 0.001), and accrued significantly greater healthcare costs (

Abstract 18: real-time proportional control of a neuroprosthetic hand by a rodent regenerative peripheral nerve interface.

180,330 versus

Electrical stimulation protocol to maintain mass and contractile force in denervated muscles

66,256, p < 0.001). As such, the risk stratification tool appropriately demonstrated that higher risk patients experienced increased length of primary hospital stay (p < 0.001), more readmissions (p < 0.001). higher rates of mortality (p < 0.001), and accrued greater cost (p < 0.001)

Abstract P18: Validating Regenerative Peripheral Nerve Interface Function in Relationship to Hind Limb Kinematics during Treadmill Locomotion

27 Volume 133, Number 3 (Supplement) • PSRC Abstract Supplement F ray, M arch 7, 2014 ConClusion: Comparisons of electrophysiological responses, muscle mass, and histology indicated that sRPNI muscle and nerve fiber recovery approached equivalence. These findings demonstrate that freely transferred muscle becomes reinnervated and viable when neurotized by a transected sensory nerve. Furthermore, electrophysiological signal is successfully transmitted between the sRPNI and residual nerve. Through electrical stimulation of this functional sRPNI, there is enormous potential for enhancing the recovery and quality of life of thousands of amputees by restoring the sense of touch.