Muscle Action Potential Duration Research Articles

Evaluation of electrophysiological changes before and after pramipexole treatment in patients diagnosed with idiopathic restless legs syndrome

Background and purpose – Restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs, frequently accompanied by unpleasant sensations. In this study, we aimed to determine the changes in electrophysiological tests including Fwave responses and H-reflex parameters in patients with idiopathic RLS after pramipexole medication. Methods –This prospective study was conducted with twenty newly diagnosed, idiopathic RLS patients. The electrophysiological parameters, specifically F-wave duration (FWD), the duration of related compound muscle action potential (CMAPD), and FWD/ CMAPD ratio, the ratio of maximum H-reflex amplitude(H) to maximum M-response amplitude (M)(H/M) were recorded in patients with idiopathic RLS before and after pramipexole medication. Results – The results revealed significant improvements in specific electrophysiolo gical parameters after pramipexole use. We observed a significant decrease in FWD, CMAPD, and FWD/CMAPD values after pramipexole treatment suggesting a reduction in motor neuron excitability. We also obser ved a significant decrease in H/M ratio after pramipexole medication indicating reduced spinal motor neuron excitability. Conclusion – This study demonstrated significant improvement in specific electrophysiological parameters following pramipexole treatment in patients with idiopathic RLS. The findings provide better understanding of the effects of pramipexole on nerve function and may contribute to the development of a monitoring tool and lead to more targeted treatments and interventions for RLS, improving the overall management and care for patients’ outcomes and quality of life with this debilitating condition.

Compound Muscle Action Potential and Myosin-Loss Pathology in Patients With Critical Illness Myopathy: Correlation and Prognostication.

Prolonged compound muscle action potential (CMAP) duration and preferential loss of myosin are considered the diagnostic hallmarks of critical illness myopathy (CIM); however, their correlation and prognostic values have not been studied. We aimed to investigate the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. We searched the Mayo Clinic Electromyography Laboratory databases (1986-2021) for patients diagnosed with CIM on the basis of prolonged distal CMAP durations (>15 msec in fibular motor nerve studies recording over the tibialis anterior or >8 msec in other motor nerves) and needle EMG findings compatible with myopathy. Electrodiagnostic studies were generally performed within 24 hours after weakness became noticeable. We included only patients who underwent muscle biopsy. Clinical, electrophysiologic, and myopathologic data were reviewed. We conducted myosin/actin ratio analysis when muscle tissue was available. We used the Fisher exact test for categorical data comparisons and the Mann-Whitney 2-tailed test for continuous data. We applied the Kaplan-Meier technique to analyze survival rates. Twenty patients (13 female patients) were identified [median age at diagnosis of 62.5 years (range: 19-80 years)]. The median onset of weakness was 24 days (range: 1-128) from the first day of intensive care unit admission. Muscle biopsy showed myosin loss in 14 patients, 9 of whom had >50% of myofibers affected (high grade). Type 2 fiber atrophy was observed in 19 patients, 13 of whom also had myosin loss. Patients with myosin loss had higher frequency of steroid exposure (14 vs 3; p = 0.004); higher median number of necrotic fibers per low-power field (2.5 vs 1, p = 0.04); and longer median CMAP duration (msec) of fibular (13.4 vs 8.75, p = 0.02), tibial (10 vs 7.8, p = 0.01), and ulnar (11.1 vs 7.95, p = 0.002) nerves compared with those without. Only patients with high-grade myosin loss had reduced myosin/actin ratios (<1.7). Ten patients died during median follow-up of 3 months. The mortality rate was similar between patients with and without myosin loss. Patients with high-grade myosin loss had a lower overall survival rate than those with low-grade or no myosin loss, but this was not statistically significant (p = 0.05). Myosin loss occurred in 70% of the patients with CIM with prolonged CMAP duration. Longer CMAP duration predicts myosin-loss pathology. The extent of myosin loss marginally correlates with the mortality rate. Our findings highlight the potential prognostic values of CMAP duration and myosin loss severity in predicting disease outcome.

Compound Muscle Action Potential (CMAP) Duration and Myosin Loss in Patients with Critical Illness Myopathy: Correlation and Prognostication (P1-11.005)

Compound Muscle Action Potential (CMAP) Duration and Myosin Loss in Patients with Critical Illness Myopathy: Correlation and Prognostication (P1-11.005)

New Measurement in the Diagnosis of Critical Illness Myopathy: Stimulus Intensity and Compound Muscle Action Potential Duration Relationship (P1-11.013)

New Measurement in the Diagnosis of Critical Illness Myopathy: Stimulus Intensity and Compound Muscle Action Potential Duration Relationship (P1-11.013)

Restless Legs Syndrome in Hemodialysis Patients: Clinical and Electrophysiological Study.

Hemodialysis-related restless legs syndrome (HD-RLS) is a common sensorial and motor disorder. The diagnosis of this disease is based on clinical criteria, and it has recently been proposed to use physiological parameters of the nerves related to the duration of the F wave as a supplementary diagnostic modality. The aim of the study is to determine the value of these parameters in the diagnosis of HD-RLS by comparing the differences between patients with HD-RLS and hemodialysis patients without RLS (HD-nRLS). A total of 20HD-RLS patients, 33HD-nRLS patients, and 30 age-and gender-matched healthy controls (HCs) were included in the study. The motor nerve conduction of the median and ulnar nerves in the upper limbs, as well as the tibial and peroneal nerves in the bilateral lower limbs, and the sensory nerve conduction of the sural nerve bilaterally and the superficial peroneal nerve, along with the F waves of the ulnar nerves, median nerve, and bilateral tibial nerve, were assessed. Both groups of HD patients had variable levels of axonal degeneration and demyelination, with the HD-RLS patients having more severe lower limb involvement. The HD-RLS patients showed an extension of the F-wave duration (FWD) of the bilateral tibial, median, and ulnar nerves, along with an increased ratio between FWD and compound muscle action potential duration (CMAPD). Peripheral neuropathy occurs in patients with HD-RLS, and the FWD/CMAPD ratio could potentially serve as an adjunctive diagnostic tool for HD-RLS.

High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

BackgroundWe proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept.MethodsPhase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks.The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables.ResultsThe primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product.ConclusionsEven if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory.Trial registrationClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

Cdon ablation in motor neurons causes age-related motor neuron degeneration and impaired sciatic nerve repair.

The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown. Hb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1G93A ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed. Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63±0.35 vs. 3.93±0.22s for f/f, P<0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79±5.74 vs. 79.39±3.77% fully occupied neuromuscular junctions for f/f, P<0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88±0.13 vs. 1.43±0.48μm for f/f, P<0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment. Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.

Markedly prolonged compound muscle action potential duration in a patient with coronavirus disease 2019 related critical illness myopathy

AbstractA 56‐year‐old man admitted with coronavirus disease 2019 (COVID‐19) became severely ill, required ventilator support and intensive care unit management. After ventilator weaning, he was found to have quadriparesis. Guillain–Barré syndrome (GBS) was suspected and administration of high‐dose intravenous immunoglobulin (IVIg) was considered. However, markedly prolonged compound muscle action potential (CMAP) duration was observed, leading to a diagnosis of critical illness myopathy (CIM). Therefore, IVIg was not given at all, and supportive care was continued. A good functional recovery was obtained. Prolonged CMAP duration is a characteristic finding to CIM. CIM following severe COVID‐19 infection is probably common, although the diagnostic value of prolonged CMAP duration is not widely recognized. This characteristic finding deserves more attention because it contributes to early differentiation between CIM and GBS and the use of IVIg in patients with COVID‐19 may cause thrombotic complications and worsen the prognosis.

Surface electroneurography of the tibial nerve in dogs

Electroneurography measures the speed of the action potential after nerve stimulation. The aim of this study was to evaluate the motor nerve conduction velocity in the tibial nerve after surface stimulation in healthy dogs, to correlate the obtained data by biological factors, and to compare these results with published findings utilizing needle electrodes. The study was performed in 11 clinically healthy dogs without anaesthesia. There were significant correlations among several indicators (age, limb length, conduction velocity, latency and duration of compound muscle action potentials). Age was found to have a significant effect on the duration of the compound muscle action potential from both stimulation sites (proximal/distal; r = 0.68, r = 0.71, P &lt; 0.05), but there was no effect on the conduction velocity or amplitude of the compound muscle action potentials. Limb length was found to have a significant effect on the duration of the compound muscle action potential from the distal stimulation site (r = 0.64, P &lt; 0.05), a significant effect on the conduction velocity (r = −0.91, P &lt; 0.01), and a significant effect on the amplitude of the compound muscle action potential from both stimulation sites (proximal/distal; r = −0.76, r = −0.63, P &lt; 0.01, P &lt; 0.05 respectively). These results indicate that limb length should be considered as the most important biological factor in tibial nerve conduction studies and that electroneurography in dogs could be performed non-invasively, without a danger of infection, haematomas or complications related to anaesthesia.

Compound muscle action potential duration ratio for differentiation between Charcot-Marie-Tooth disease and CIDP

To elucidate the utility of the proximal to distal compound muscle action potential (CMAP) duration ratio to distinguish between demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) compared with nerve ultrasound. Thirty-nine demyelinating CMT patients and 19 CIDP patients underwent nerve conduction studies (NCS) and nerve ultrasound. NCS parameters including CMAP duration ratio calculated by dividing the value at the proximal site by that at the distal site and nerve cross-sectional area (CSA) measured by ultrasound were compared between the two groups. The diagnostic sensitivity and specificity of each parameter were analysed. CMT patients showed a significantly lower CMAP duration ratio than CIDP patients (p<0.05). The area under the curve (AUC) value of the CMAP duration ratio exceeded 0.95 when CMT was considered "positive", and a cut-off value of 1.13 resulted in high diagnostic sensitivity and specificity (84.6 and 100% for median nerve, 97.4 and 85.7% for ulnar nerve, respectively), whereas the AUC value of nerve CSA ranged from 0.70 to 0.81. The CMAP duration ratio could effectively distinguish between demyelinating CMT and CIDP. Adding the CMAP duration ratio to a routine NCS may improve the accuracy of the diagnosis of demyelinating CMT.

Study of total duration of distal compound muscle action potential in demyelinating and axonal Guillain-Barre’ syndrome

ABSTRACT Objectives Electrophysiology plays a crucial role in Guillain-Barré syndrome (GBS) diagnosis and subtype classification. The aim of our study was to assess the potential role of distal compound muscle action potential (dCMAP) for early differentiation between acute inflammatory demyelinating polyneuropathy (AIDP) and axonal GBS. Methods We retrospectively reviewed the medical records of 24 subjects with AIDP and 18 subjects with axonal GBS. We built up receiver operating characteristic curves for total dCMAP duration and negative phase of dCMAP duration, in order to derive cut-off values able to differentiate between AIDP and axonal GBS. Results The total duration of dCMAP was significantly prolonged in AIDP compared to axonal GBS. AUCs, odds ratio and positive predictive values were higher for total duration than for negative peak duration. Nerve conduction parameters in the lower limbs were more sensitive than those in the upper limbs in distinguishing AIDP from axonal GBS. Discussion Total duration of dCMAP dispersion may capture an adjunctive component of distal demyelination, not measured by the more traditional parameters and may thus represent a useful tool for early differentiation between AIDP and axonal GBS.

Temporal Dispersion and Duration of the Distal Compound Muscle Action Potential Do Not Distinguish Diabetic Sensorimotor Polyneuropathy From Chronic Inflammatory Demyelinating Polyneuropathy.

ObjectiveTo investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP.MethodsWe performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline.ResultsWe included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP.ConclusionMeasures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation.SignificanceThere are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients.

F wave in restless legs syndrome, as an electrophysiological response of clinical relief

ABSTRACT Objective The study aimed to evaluate the impact of postural changes on the F wave-related parameters and whether those changes were associated with clinical relaxation, which was achieved in restless legs syndrome patients with standing up. Methods F wave duration (FWD), compound muscle action potential duration (CMAPD), and FWD/CMAPD ratio were evaluated in supine and upward positions in 18 restless legs syndrome patients and compared with 18 age and gender-matched healthy volunteers. Results FWD/CMAPD was significantly higher for the tibial nerve at supine position (p = 0.043) but not at upright position (p = 0.206) and for ulnar nerve, both at supine (p = 0.007) and upright positions (p = 0.023) in RLS patients compared to controls. Ulnar FWD decreased significantly at the upright position in both control and RLS patients (p = 0.035, p = 0.028, respectively). CMAPD decreased only in the control group with standing up for both ulnar and tibial nerves (p = 0.048, p = 0.017, respectively). Discussion Ulnar and tibial FWD/CMAPD ratios increased in RLS patients compared to controls. However, FWD/CMAPD was not affected by the posture within the groups. Postural change seems to be a factor that decreased ulnar FWD both in RLS patients and the control group. Ulnar and tibial CMAPD reduced only in healthy controls with an upright position. Tibial and ulnar FWD/CMAPD ratios are favorable electrophysiological parameters diagnosing RLS. The tibial FWD/CMAPD ratio loses its significance only when the patient stands up, reflecting the clinical relief achieved with the postural change.

Duration and temporal dispersion measurements in CIDP subjects from the Polyneuropathy And Treatment with Hizentra (PATH) study

Abstract:&#x0D; Introduction: Distal compound muscle action potential (dCMAP) duration and temporal dispersion (TD) are electrophysiological hallmarks of demyelination and important for the diagnosis of CIDP. While the impact of CIDP treatment on other nerve conduction parameters has been examined, the effects on dCMAP and TD remain unexplored. The aim of the study was to examine the impact of withdrawal of immunoglobulin treatment on dCMAP duration and TD, and also the influence of the measurement technique on dCMAP duration and TD.&#x0D; Methods: Nerve conduction studies were analyzed from the PATH (Polyneuropathy And Treatment with Hizentra) study which randomized patients with CIDP to two doses of IgPro 20 and placebo. Distal CMAP duration and TD were obtained by two methods of measurements (D1 and D2, TD1 and TD2) from the median and peroneal nerves. &#x0D; Results: The dCMAP and TD were obtained from 389 tracings. While the two methods of measurement showed differences in D1 and D2 with D2 longer than D1 in all the three groups, there was no difference between the TD1 and TD2. There was no difference at baseline in dCMAP duration or TD among the three groups. At the end of treatment, patients in the placebo arm had no worsening of dCMAP and TD compared to baseline or the treated groups.&#x0D; Conclusion: dCMAP duration and TD did not show a difference between treated and placebo groups, and may be less sensitive measures than other nerve conduction parameters when evaluating changes in treatment. The method of dCMAP duration measurement does not affect TD as long as a consistent method is followed.&#x0D;

PHRENIC NERVE CONDUCTION STUDY IN HEALTHY POPULATION

The phrenic nerve provides the primary motor supply to the diaphragm Phrenic nerve conduction study provides a sensitive indicator of phrenic nerve function when the nerve is affected either by local lesions or by generalized neuropathies. Percutaneous phrenic nerve stimulation is an easy and rapid procedure that achieves successful stimulation of the nerve. It is associated with little or no discomfort. Amplitude, latency, area, and duration are measures used to evaluate phrenic nerve integrity. Only limited data has however been published on normative data of phrenic nerve conduction study. Aim of the work The aim of this study was to determine normative values of phrenic nerve conduction parameters in healthy population.Subjects & Methods • Seventy-three healthy individuals (47 men and 26 women) aged from 18 to 61 years participated in the study. • Motor conduction studies of the phrenic nerve were performed bilaterally both during inspiration and expiration. The phrenic nerve was stimulated at the posterior border of the sternocleidomastoid muscle at the level of the cricoid cartilage. Recording was made from both sternal and costal diaphragm. • Measured parameters were latency, amplitude, area and duration of the diaphragmatic compound muscle action potential )DCMAP( at each recording site. Side-side differences were determined.

Neurogenic vs. Myogenic Origin of Acquired Muscle Paralysis in Intensive Care Unit (ICU) Patients: Evaluation of Different Diagnostic Methods.

Introduction. The acquired muscle paralysis associated with modern critical care can be of neurogenic or myogenic origin, yet the distinction between these origins is hampered by the precision of current diagnostic methods. This has resulted in the pooling of all acquired muscle paralyses, independent of their origin, into the term Intensive Care Unit Acquired Muscle Weakness (ICUAW). This is unfortunate since the acquired neuropathy (critical illness polyneuropathy, CIP) has a slower recovery than the myopathy (critical illness myopathy, CIM); therapies need to target underlying mechanisms and every patient deserves as accurate a diagnosis as possible. This study aims at evaluating different diagnostic methods in the diagnosis of CIP and CIM in critically ill, immobilized and mechanically ventilated intensive care unit (ICU) patients. Methods. ICU patients with acquired quadriplegia in response to critical care were included in the study. A total of 142 patients were examined with routine electrophysiological methods, together with biochemical analyses of myosin:actin (M:A) ratios of muscle biopsies. In addition, comparisons of evoked electromyographic (EMG) responses in direct vs. indirect muscle stimulation and histopathological analyses of muscle biopsies were performed in a subset of the patients. Results. ICU patients with quadriplegia were stratified into five groups based on the hallmark of CIM, i.e., preferential myosin loss (myosin:actin ratio, M:A) and classified as severe (M:A < 0.5; n = 12), moderate (0.5 ≤ M:A < 1; n = 40), mildly moderate (1 ≤ M:A < 1.5; n = 49), mild (1.5 ≤ M:A < 1.7; n = 24) and normal (1.7 ≤ M:A; n = 19). Identical M:A ratios were obtained in the small (4–15 mg) muscle samples, using a disposable semiautomatic microbiopsy needle instrument, and the larger (>80 mg) samples, obtained with a conchotome instrument. Compound muscle action potential (CMAP) duration was increased and amplitude decreased in patients with preferential myosin loss, but deviations from this relationship were observed in numerous patients, resulting in only weak correlations between CMAP properties and M:A. Advanced electrophysiological methods measuring refractoriness and comparing CMAP amplitude after indirect nerve vs. direct muscle stimulation are time consuming and did not increase precision compared with conventional electrophysiological measurements in the diagnosis of CIM. Low CMAP amplitude upon indirect vs. direct stimulation strongly suggest a neurogenic lesion, i.e., CIP, but this was rarely observed among the patients in this study. Histopathological diagnosis of CIM/CIP based on enzyme histochemical mATPase stainings were hampered by poor quantitative precision of myosin loss and the impact of pathological findings unrelated to acute quadriplegia. Conclusion. Conventional electrophysiological methods are valuable in identifying the peripheral origin of quadriplegia in ICU patients, but do not reliably separate between neurogenic vs. myogenic origins of paralysis. The hallmark of CIM, preferential myosin loss, can be reliably evaluated in the small samples obtained with the microbiopsy instrument. The major advantage of this method is that it is less invasive than conventional muscle biopsies, reducing the risk of bleeding in ICU patients, who are frequently receiving anticoagulant treatment, and it can be repeated multiple times during follow up for monitoring purposes.

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.

Inhibition of Advanced Glycation End Products Formation Attenuates Cardiac Electrical and Mechanical Remodeling and Vulnerability to Tachyarrhythmias in Diabetic Rats

Diabetic patients with cardiomyopathy show a higher incidence of arrhythmias and sudden death. Chronic hyperglycemia induces the formation of advanced glycation end products (AGEs), which contribute to the pathogenesis of diabetic cardiomyopathy. This study investigated whether inhibition of AGEs formation by aminoguanidine (AG) could prevent cardiac electromechanical and arrhythmogenic remodeling in diabetes mellitus. Streptozotocin-induced diabetic rats received AG (100 mg/kg daily, i.p.) or vehicle (normal saline, i.p.) for 5 weeks. The rats underwent hemodynamic recording to evaluate cardiac function, and heart preparations were used to determine the electrical, mechanical, and biochemical functions. In vitro high glucose-induced AGEs formation, reactive oxygen species (ROS) generation, and action potential changes were examined in HL-1 atrial cells. AG treatment improved the diabetes-induced depression in left ventricular pressure and the relaxation rate, and normalized the prolongation of QTc intervals in anesthetized rats. AG reduced the vulnerabilities to atrial and ventricular tachyarrhythmias in perfused diabetic hearts. AG normalized the prolonged action potential duration in diabetic atrial and ventricular muscles, which was correlated with the restoration of both transient outward (I to) and steady-state outward (I SS) K+ current densities in cardiomyocytes. The abnormal kinetics of Ca2+ transients and contraction were reversed in cardiomyocytes from AG-treated diabetic rats, along with parallel preservation of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) expression. Furthermore, ex vivo and in vitro studies showed AG attenuated AGEs and ROS formation. Thus, long-term administration of AG ameliorated cardiac electromechanical remodeling and arrhythmogenicity in diabetic rats and may present an effective strategy for the prevention of diabetes-associated arrhythmias.

Compound muscle action potential duration in critical illness neuromyopathy.

We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018.

3-2-07. Clinical application of the measurement of muscle fiber conduction velocity using direct muscle stimulation for critical illness myopathy (CIM)

Measurement of the muscle fiber conduction velocity (MFCV) using direct muscle stimulation has been considered to be useful for the evaluation of critical illness myopathy (CIM), although there are rather few reports on this issue. Subjects consisted of 2 normal volunteers, 4 patients with myositis, and 1 patient with CIM. Stimulation was given to the muscle using a monopolar needle and the muscle fiber action potentials (MFAPs) was recorded using a concentric needle electrode. MFCV was calculated based on the onset latencies of the MFAPs recorded at different intramuscular locations. As results, MFCV was 4–5 m/s in the CIM patient. It was 4.2 and 4.8 m/s on average in control subjects, and was 3.6–4.3 m/s in patients with myositis. The CIM patient presented with markedly prolonged duration of the compound muscle action potential (CMAP). Normal MFCV in the CIM patient may suggest that the prolonged CMAP duration in CIM may not be due to the slowed MFCV, but to other mechanisms. MFCV measurement is a difficult technique, and its diagnostic role is yet to be documented, including for CIM.