Rat Peroneal Nerve Research Articles

Ultraflexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-Dimension, Cuff-Less Microneedle Electrode Array.

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are 1) how to apply them to small peripheral nerves, and 2) how to minimize chronic reactivity. A flexible microneedle nerve array (MINA) is developed, which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. The design, fabrication, acute recording, and chronic reactivity to an implanted MINA, are presented. Distinctive units are identified in the rat peroneal nerve. The authors also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two time-points. The tissue response is investigated at 1-week and 6-week time-points, including two sham groups and two MINA-implanted groups. These conditions are quantified in the left vagus nerve of rats using histomorphometry. Micro computed tomography (micro-CT) is added to visualize and quantify tissue encapsulation around the implant. MINA demonstrates a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

Nerve transfer with 3D-printed branch nerve conduits.

BackgroundNerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve. Usually, nerve transfer is performed in an end-to-end manner, which will lead to functional loss of the donor nerve. In this study, we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer.MethodsCustomized branch conduits were constructed using gelatine-methacryloyl by 3D printing. The nerve conduits were characterized both in vitro and in vivo. The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation.ResultsThe results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit. A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats. In this process, the two branches were connected to the distal tibial nerve and peroneal nerve. It was found that the two nerves were successfully repaired with functional recovery.ConclusionsIt is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve. This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer.

Does cryoneurolysis result in persistent motor deficits? A controlled study using a rat peroneal nerve injury model

BackgroundCryoneurolysis of peripheral nerves uses localised intense cold to induce a prolonged block over multiple weeks that has the promise of providing potent analgesia outlasting the duration of postoperative pain...

Repair of peripheral nerve defects by nerve transposition using small gap bio-sleeve suture with different inner diameters at both ends.

During peripheral nerve transposition repair, if the diameter difference between transposed nerves is large or multiple distal nerves must be repaired at the same time, traditional epineurial neurorrhaphy has the problem of high tension at the suture site, which may even lead to the failure of nerve suture. We investigated whether a small gap bio-sleeve suture with different inner diameters at both ends can be used to repair a 2-mm tibial nerve defect by proximal transposition of the common peroneal nerve in rats and compared the results with the repair seen after epineurial neurorrhaphy. Three months after surgery, neurological function, nerve regeneration, and recovery of nerve innervation muscle were assessed using the tibial nerve function index, neuroelectrophysiological testing, muscle biomechanics and wet weight measurement, osmic acid staining, and hematoxylin-eosin staining. There was no obvious inflammatory reaction and neuroma formation in the tibial nerve after repair by the small gap bio-sleeve suture with different inner diameters at both ends. The conduction velocity, muscle strength, wet muscle weight, cross-sectional area of muscle fibers, and the number of new myelinated nerve fibers in the bio-sleeve suture group were similar to those in the epineurial neurorrhaphy group. Our findings indicate that small gap bio-sleeve suture with different inner diameters at both ends can achieve surgical suture between nerves of different diameters and promote regeneration and functional recovery of injured peripheral nerves.

Corrigendum to "Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)".

[This corrects the article DOI: 10.1093/ecam/neq062.].

End-to-side versus end-to-end neurorrhaphy at the peroneal nerve in rats

To evaluate three different kinds of neurorrhaphy of the peroneal nerve. Eigthy rats were divided into 5 groups. Control: nerve had no intervention. End-to-end (EE): nerve was cut and elongated with a nerve graft with two end-to-end neurorrhaphies. End-to-side (ES): nerve was cut and sutured to the graft with at the lateral side of the nerve. Side-to-end (SE): the nerve was cut and sutured to the graft with end-to-end neurorrhaphy. Denervated: nerve was cut and both endings were buried into the muscle. The evaluation was done by walking track analysis, electrophysiology, body mass, cranial tibial muscle mass, nerve and muscle fibers morphometry. The EE, ES and SE have the same potential of reinnervation. There is no functional or histological difference between these different types of neurorrhaphy.

Development of battery-free neural interface and modulated control of tibialis anterior muscle via common peroneal nerve based on triboelectric nanogenerators (TENGs)

Flexible and stretchable electronics, also known as e-skin, have been a technology to create diversified sensors and wearable devices. Implantable bioelectronics have recently been recognized as a promising research field to modulate biological signals and treat many diseases and pathological conditions. The marriage of two technologies gives us a new cutting-edge research area, i.e., implantable flexible electronics. While strain sensors, ECG sensors, pH sensors, temperature sensors and LED chips have been integrated together as a novel platform for measuring physiological signals, one of critical challenges for long-term use of such devices is a reliable power source with sound output power. To support operation of the implantable bioelectronics, triboelectric nanogenerators (TENGs) have recently been explored, as a promising technology to harvest energy, as the concept of scavenging human body energy into useful electrical power.In this work, we investigate stacked TENGs with output voltage of 160 Vp-p and a short circuit current of 6.7µA as a potential power source for neural stimulation using flexible and adjustable neural interfaces. To advance a generic design of flexible neural interfaces which is good at sciatic nerve recording and stimulation, we optimize a new flexible sling electrode and successfully achieve neural signal recording with different amplitudes and latencies. More importantly, successful selective stimulation achieved in this work proves that the flexible sling electrode is a good generic neural interface. We demonstrate direct stimulation of a sciatic nerve and a common peroneal nerve in rats by the TENGs connected with the suggested interface and a pair of Pt/Ir wires, respectively, while monitoring muscle signals. The muscle contraction can be controlled by the operation of the TENGs. This prove-concept result indicates that this technology could be the way of realizing battery-free wearable neuromodulators in the future.

Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb.

Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation.

Immunohistochemical, Ultrastructural and Functional Analysis of Axonal Regeneration through Peripheral Nerve Grafts Containing Schwann Cells Expressing BDNF, CNTF or NT3

We used morphological, immunohistochemical and functional assessments to determine the impact of genetically-modified peripheral nerve (PN) grafts on axonal regeneration after injury. Grafts were assembled from acellular nerve sheaths repopulated ex vivo with Schwann cells (SCs) modified to express brain-derived neurotrophic factor (BDNF), a secretable form of ciliary neurotrophic factor (CNTF), or neurotrophin-3 (NT3). Grafts were used to repair unilateral 1 cm defects in rat peroneal nerves and 10 weeks later outcomes were compared to normal nerves and various controls: autografts, acellular grafts and grafts with unmodified SCs. The number of regenerated βIII-Tubulin positive axons was similar in all grafts with the exception of CNTF, which contained the fewest immunostained axons. There were significantly lower fiber counts in acellular, untransduced SC and NT3 groups using a PanNF antibody, suggesting a paucity of large caliber axons. In addition, NT3 grafts contained the greatest number of sensory fibres, identified with either IB4 or CGRP markers. Examination of semi- and ultra-thin sections revealed heterogeneous graft morphologies, particularly in BDNF and NT3 grafts in which the fascicular organization was pronounced. Unmyelinated axons were loosely organized in numerous Remak bundles in NT3 grafts, while the BDNF graft group displayed the lowest ratio of umyelinated to myelinated axons. Gait analysis revealed that stance width was increased in rats with CNTF and NT3 grafts, and step length involving the injured left hindlimb was significantly greater in NT3 grafted rats, suggesting enhanced sensory sensitivity in these animals. In summary, the selective expression of BDNF, CNTF or NT3 by genetically modified SCs had differential effects on PN graft morphology, the number and type of regenerating axons, myelination, and locomotor function.

Effect of electrical stimulation of the cranial tibial muscle after end-to-side neurorrhaphy of the peroneal nerve in rats

To investigate the efficiency of electrical stimulation in the muscle maintenance and nerve regeneration after end-to-side neurorrhaphy (ESN). Sixty male Wistar rats (Rattus norvegicus) were divided into four experimental groups. Control group (Control), Denervated Group (Denervated); Group with End-to-side neurorrhaphy (ESN); Group with End-to-side neurorrhaphy and electrical stimulation (ESN + ES). We perform electrical stimulation in rats after they had undergone muscle reinnervation by ESN. We collected morphometric and functional data. When comparing the mass of the treated side of cranial tibial muscle (CTM) and that of normal side of CTM, the group ESN + ES (26.12%) exhibited lower mass loss than that of group ESN (37.23%). The peroneal functional index showed that group ESN + ES equaled that of the Control group and showed an evolution of 60.5% while group ESN showed an evolution of 9.5%. In measuring maximum strength of CTM, the group ES + ESN outperformed group ESN. The muscle and nerve morphometry showed superiority of group ES+ESN over ESN group in all parameters. Electrical stimulation is an effective means of maintaining functional muscle and nerve regeneration after end-to-side neurorrhaphy.

Neuroregenerative Potential of Lion's Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Higher Basidiomycetes), in the Treatment of Peripheral Nerve Injury (Review)

We present a model case study of the activity of aqueous extract of Hericium erinaceus fresh fruit bodies in promoting functional recovery following crush injury to the peroneal nerve in adult female Sprague-Dawley rats. The aim was to explore the possible use of this mushroom in nerve repair. The activities of aqueous extract were compared to activities exhibited by mecobalamin (vitamin B12), which has been widely used in the treatment of peripheral nerve disorders. Analysis of walking track indicated that return of hind limb function and normal toe spreading occurred earlier in treated groups than in the negative control (non-treated) group. Regeneration of axons and reinnervation of motor endplates/neuromuscular junction in extensor digitorum longus muscle of rats in treated groups developed better than in the negative control group. Further, immunofluorescence studies also showed that dorsal root ganglia neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt and MAPK signaling pathways as well as c-Jun and c-Fos genes compared to the negative control group. Akt cascade plays a major role in mediating neurotrophin-promoted cell survival, while MAPK cascade is involved in mediating neurite outgrowth. Immediate early gene expression was also involved in the cascade of events leading to regeneration. Local axonal protein synthetic machinery was also enhanced in the distal segments of crushed nerves in treated groups. Therefore, daily oral administration of H. erinaceus could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration

The inhibitory growth environment of myelin and extracellular matrix proteoglycans in the central nervous system may be overcome by elevating neuronal cAMP or degrading inhibitory proteoglycans with chondroitinase ABC (ChABC). In this study, we asked whether similar mechanisms operate in peripheral nerve regeneration where effective Wallerian degeneration removes myelin and extracellular proteoglycans slowly. We repaired transected common peroneal (CP) nerve in rats and either elevated cAMP in the axotomized neurons by subcutaneous rolipram, a specific inhibitor of phosphodiesterase IV, and/or promoted degradation of proteoglycans in the distal nerve stump by local ChABC administration. Rolipram treatment significantly increased the number of motoneurons that regenerated axons across the repair site at 1 and 2 weeks, and increased the number of sensory neurons that regenerated axons across the repair site at 2 weeks. Local application of ChABC had a similar effect to rolipram treatment in promoting motor axon regeneration, the effect being no greater when rolipram and ChABC were administered simultaneously. We conclude that blocking inhibitors of axon regeneration by elevating cAMP or degrading proteoglycans in the distal nerve stump promotes peripheral axon regeneration after surgical repair of a transected nerve. It is likely that elevated cAMP is sufficient to encourage axon outgrowth despite the inhibitory growth environment such that simultaneous enzymatic proteoglycan degradation does not promote more axon regeneration than either elevated cAMP or proteoglycan degradation alone.

Effects of Metal Fragments on Nerve Healing in Extremity Injuries Using a Rat Peroneal Nerve Model

On the modern battlefield, the majority of injuries currently seen are to the extremities, often involving a large number of metallic fragments. Although they are typically left in place, the effects of these retained metal fragments on nerve healing have not been studied. In a rat model, the right peroneal nerve was surgically sectioned and reanastomosed (control group). In the study group, metal fragments from an artillery casing were placed around the reanastomosed peroneal nerve. Functional recovery in both groups was evaluated over a 4-week period by measuring maximum ankle dorsiflexion captured on video as the animals walked through a tunnel. Morphologic analyses included distal and proximal axon counts, measurement of nerve fiber and axon diameter ratios, and myelin thickness. A significant decrease (p < 0.05) in return toward baseline for the rats' ankle angle in the nerves exposed to metal fragments was noted at weeks 2 through 4. Distal axon counts were significantly less (p < 0.05) in the metal fragment group for weeks 1 through 4. Proximal axon counts were increased in both groups, with a greater (p < 0.05) increase in the metal fragment group. Functional recovery after rat peroneal nerve transection and repair is decreased when metal fragments are placed in and around the injury site. Select histologic indicators of nerve regeneration showed decreased healing when exposed to metal fragments. Further studies of functional recovery in patients sustaining penetrating injuries from bullets or explosive devices are indicated.

Influência da irradiação do laser na regeneração nervosa em diferentes locais de tratamento

OBJETIVO: Verificar a influência do laser de baixa intensidade de AsGaAl na lesão por esmagamento do nervo peroneiro de ratos através da avaliação funcional da marcha nos diferentes locais de irradiação. MÉTODOS: Foram utilizados 53 ratos, divididos em seis grupos: normal, lesado não tratado, lesado e tratado placebo, lesado e tratado na medula, lesado e tratado no nervo, lesado e tratado em ambos (nervo e medula). O esmagamento do nervo peroneiro foi realizado por meio de uma pinça e subsequente tratado com laser por 28 dias consecutivos. Na avaliação funcional foram analisadas as impressões das pegadas, registradas pela câmera de vídeo em uma passarela de acrílico, no pré-operatório e aos 14º, 21º e 28º dias de pós-operatório, e avaliadas na fórmula PFI por meio do software. RESULTADOS: Na avaliação funcional da marcha foram encontradas diferenças significantes somente no 14º dia de pós-operatório. CONCLUSÃO: A irradiação do laser AsGaAl de baixa intensidade foi capaz de acelerar e potencializar o processo de regeneração nervosa periférica de ratos no 14º dia de pós-operatório, de acordo com a avaliação funcional da marcha, tanto para o grupo tratado na medula quanto para o grupo tratado no nervo.

Functional Recovery Enhancement Following Injury to Rodent Peroneal Nerve by Lion's Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae)

Peripheral nerve injury represents a huge burden to society. Following peripheral nerve injury, improved behavioral outcome may be the most important evidence of functionality of axonal regeneration after any repair strategy. Nerve-crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruitbodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats with a long-term view toward the possible use of this mushroom in the treatment of nerve injury. Functional recovery was assessed in the behavioral experiment by walking-track analysis and toe-spreading reflex. The peroneal functional index (PFI) was determined before surgery and after surgery, as the rats showed signs of recovery. Analysis of the PFI indicated that the return of hind-limb function occurred by day 10 to 14 and by day 14 to 17 in the treated and control (nontreated) groups, respectively. Normal toe-spreading in the crushed limb was achieved by day 7 to 10 and day 12 to 17 in the treated and control group, respectively. These results suggest that daily administration of aqueous extract of H. erinaceus fresh firuitbodies has a beneficial effect on the recovery of injured rat peroneal nerve in the early stages of regeneration. The PFI and toe-spreading reflex improved faster in the treated group than in the nontreated group.

The influence of continuous exposure to 50 Hz electric field on nerve regeneration in a rat peroneal nerve crush injury model

The effect of power frequency electric field (EF) on nerve regeneration was investigated on a rat peroneal nerve crush injury model. The animals were assigned to three groups: 50 Hz EF and Static EF groups were exposed at 10 kV/m. The sham group was kept in the same setting without any EF applications. EF was uninterruptedly applied for 21 days postoperatively. Repeated measures analysis of daily walking tracks during EF exposure demonstrated lower toe spread recovery (TSR) in the 50 Hz EF group. Significant difference across the groups was found only at days 7, 8, 12, 16, 17, 20, and 21 when TSR was analyzed for each measurement time. Print length recovery and peroneal function index did not differ across the groups. Walking track parameters were found to recover to their baseline values by day 28 in all groups. Day 14 but not day 21 measurements revealed smaller nerve cross-sectional area, lower total regenerating axon area, and higher mean myelin debris area in 50 Hz EF group. Both day 14 and 21 measurements revealed higher total myelin debris area, lower EDL muscle weight, and lack of significant enlargement in nerve cross-section distal to the injury, compared to the normal counterpart in 50 Hz EF group. All differences were in keeping with lower rates of Wallerian degeneration and nerve regeneration in 50 Hz EF group. When walking track, histomorphometry and muscle weight are considered individually, their differences across the groups may appear to be subtle to derive a conclusion for a 50 Hz EF effect. However, their concordance with each other in direction of effect suggests that continuous 50 Hz EF exposure has a weak effect that is detrimental mostly to the rate of early nerve regeneration in this axonotmetic injury model. Recovery of walking tracks was not different between Static EF and Sham groups. This suggests that the surface charges that may indirectly affect walking behaviors of the rats, do not account for the lower recovery of TSR in 50 Hz EF group. Differences in nerve regeneration between 50 Hz EF and Static EF groups suggests that electric induction may be required for pure EF effects even though the estimated density of induced fields is not above the endogenous background level for the 50 Hz EF exposure in this study.

Decreased number of acetylcholine receptors is the mechanism that alters the time course of muscle relaxants in myasthenia gravis

In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and sensitivity can be explained by the decreased acetylcholine receptor concentration that is caused by the disease. Functional acetylcholine receptors were reduced by administration of alpha-bungarotoxin or by injecting monoclonal antibodies against rat acetylcholine receptors (experimental autoimmune myasthenia gravis). After induction of anaesthesia, the model was set up and perfusion of the tibialis anterior muscle with blood was started. After stabilization of the twitch, rocuronium or pancuronium were infused until 90% block was obtained. Twitch data and infusion data were recorded and used to calculate the time course of effect and potency. The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the alpha-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls. This study shows that the increased sensitivity to neuromuscular-blocking agents in myasthenia gravis can be accounted for by a decreased number of acetylcholine receptors. It also shows that the antegrade perfused rat peroneal nerve anterior tibialis muscle model is a suitable model to study the effects of myasthenia gravis on the time course of effect of neuromuscular blocking agents.

Effects of vascular endothelial growth factor on nerve regeneration in acellular nerve grafts.

The purpose of this study was to evaluate the effects of human recombinant vascular endothelial growth factor (VEGF-165) on peripheral nerve axonal sprouting and elongation following peripheral nerve injury and repair. Two-centimeter nerve gaps were created in rat peroneal nerves and repaired with either peripheral nerve autografts, acellular peripheral nerve isografts, or VEGF-165-treated acellular peripheral nerve isografts. Four months postoperatively, the peroneal nerves were harvested and histomorphometric analysis was performed. The reinnervated extensor digitorum longus (EDL) muscles were harvested and weighed. At the proximal nerve gap coaptation site, there was a statistically significant increase in the total number of axons and percent neural tissue in the VEGF-treated acellular nerve graft group, compared with the acellular peripheral nerve isograft and autograft groups. At the distal coaptation site, however, the total number of axons and percent neural tissue was similar in the acellular and VEGF-treated groups, which was significantly less than the autograft group. VEGF-165 treatment of acellular nerve grafts resulted in greater EDL muscle masses than acellular nerve grafts alone. VEGF treatment of acellular peripheral nerve isografts enhances axonal sprouting, resulting in an increased number of axons and percent neural tissue at the proximal nerve graft coaptation site. In the absence of any cellular elements, VEGF-impregnated acellular peripheral nerve grafts do not demonstrate enhanced axonal elongation, as noted by relatively few axons at the distal nerve graft coaptation site.

An isolated, antegrade, perfused, peroneal nerve anterior tibialis muscle model in the rat: a novel model developed to study the factors governing the time course of action of neuromuscular blocking agents.

A model of an antegrade, perfused, isolated rat peroneal nerve anterior tibial muscle was developed to study potentially important factors governing the time course of action of (nondepolarizing) neuromuscular blocking agents such as concentration, blood flow, and temperature. The model allows observation of the effects of selective changes in these factors. The authors isolated the anterior tibial muscle and cannulated the anterior tibial artery and vein, providing a way for single-pass perfusion with blood from a donor rat. A force transducer was connected to the tibialis anterior muscle and a stimulator was connected to the tibial nerve. The influence of intrinsic potency (EC90) and muscle blood flow rate on the time course of pancuronium and rocuronium was investigated. The model remained stable for at least 4 h with respect to twitch height, muscle structure and function, and blood chemistry. Doubling the muscle-blood flow resulted in a significantly faster onset and offset for both pancuronium and rocuronium. Trebling the intrinsic potency (EC90) was not associated with significant changes in the time course of action of the relaxants. The authors developed and validated a model that allows us to study biophase kinetics of neuromuscular blocking agents in the anterior tibial muscle of the rat. In this model, muscle-blood flow rather than EC90 appears to predominantly determine the onset and offset time of nondepolarizing muscle relaxants.