Natural History of Mixed and Motor Nerve Cryoablation in Humans-A Cohort Analysis.

Eight patients who underwent percutaneous cryoablation of mixed and/or motor nerves over a period of 5 years were identified. Distances from the ablation sites to origins of distal musculature were measured, and times to initial clinical recovery were collected. Strength progression over time following muscle activation was also collected and analyzed. All patients demonstrated activation of all muscles distal to the ablation, and the calculated mean rate of nerve regeneration based on distance to the origin of the assessed musculature and time to muscle activation for the group was 1.5 mm/day ± 1.1.

CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice.

Muscle atrophy is the loss of skeletal muscle mass and strength in response to diverse catabolic stimuli. At present, no effective treatments except exercise have been shown to reduce muscle atrophy clinically. Here, we report that CRISPR/Cas9-mediated genome editing through local injection into gastrocnemius muscles or tibialis anterior muscle efficiently targets the biogenesis processing sites in pre-miR-29b. In vivo, this CRISPR-based treatment prevented the muscle atrophy induced by angiotensin II (AngII), immobilization, and denervation via activation of the AKT-FOXO3A-mTOR signaling pathway and protected against AngII-induced myocyte apoptosis in mice, leading to significantly increased exercise capacity. Our work establishes CRISPR/Cas9-based gene targeting on miRNA as a potential durable therapy for the treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo.

Architectural Changes in the Medial Gastrocnemius on Sonography after Nerve Ablation in Healthy Adults.

Architectural changes in healthy muscle after denervation have not yet been reported. This study aimed to investigate architectural changes in the medial head of the gastrocnemius muscle (GCM) after aesthetic tibial nerve ablation in healthy adults using ultrasonography (US). The effects of tibial nerve ablation were verified by visual observation and surface electromyography analysis. US images of medial GCMs were taken by one trained physician using B-mode and real-time US with a linear-array probe before nerve ablation, at 1 week after nerve ablation and at 3 months after nerve ablation in an anatomic standing position with the feet about shoulder-width apart in 19 healthy adults (17 females and 2 males). Muscle thickness was significantly reduced on the left side at 1 week and 3 months after the procedure and on the right side at 3 months after the procedure (p<0.050). Although fascicle length was not significantly changed, pennation angle was significantly reduced on both sides at 3 months after the procedure (p<0.050). Muscle thickness and pennation angle of the muscle fascicle were significantly reduced, although fascicle length was not significantly changed, after tibial nerve ablation in the medial GCM of healthy adults.

Targeted ablation of the cellular inhibitor of apoptosis 1 (cIAP1) attenuates denervation-induced skeletal muscle atrophy.

BACKGROUND: Skeletal muscle atrophy is a pathological condition that contributes to morbidity in a variety of conditions including denervation, cachexia, and aging. Muscle atrophy is characterized as decreased muscle fiber cross-sectional area and protein content due, in part, to the proteolytic activities of two muscle-specific E3 ubiquitin ligases: muscle RING-finger 1 (MuRF1) and muscle atrophy F-box (MAFbx or Atrogin-1). The nuclear factor-kappa B (NF-κB) pathway has emerged as a critical signaling network in skeletal muscle atrophy and has become a prime therapeutic target for the treatment of muscle diseases. Unfortunately, none of the NF-κB targeting drugs are currently being used to treat these diseases, likely because of our limited knowledge and specificity, for muscle biology and disease. The cellular inhibitor of apoptosis 1 (cIAP1) protein is a positive regulator of tumor necrosis factor alpha (TNFα)-mediated classical NF-κB signaling, and cIAP1 loss has been shown to enhance muscle regeneration during acute and chronic injury. METHODS: Sciatic nerve transection in wild-type, cIAP1-null and Smac mimetic compound (SMC)-treated mice was performed to investigate the role of cIAP1 in denervation-induced atrophy. Genetic in vitro models of C2C12 myoblasts and primary myoblasts were also used to examine the role of classical NF-κB activity in cIAP1-induced myotube atrophy. RESULTS: We found that cIAP1 expression was upregulated in denervated muscles compared to non-denervated controls 14 days after denervation. Genetic and pharmacological loss of cIAP1 attenuated denervation-induced muscle atrophy and overexpression of cIAP1 in myotubes was sufficient to induce atrophy. The induction of myotube atrophy by cIAP1 was attenuated when the classical NF-κB signaling pathway was inhibited. CONCLUSIONS: These results demonstrate the cIAP1 is an important mediator of NF-κB/MuRF1 signaling in skeletal muscle atrophy and is a promising therapeutic target for muscle wasting diseases.

Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α.

BACKGROUND: Genistein has high estrogenic activity. Previous studies have shown beneficial effects of estrogen or hormone replacement therapy on muscle mass and muscle atrophy. OBJECTIVE: We investigated the preventive effects and underlying mechanisms of genistein on muscle atrophy. METHODS: In Expt. 1, male Wistar rats were fed a diet containing no genistein [control (CON)] or 0.05% genistein (GEN; wt:wt diet) for 24 d. On day 14, the sciatic nerve in the left hind leg was severed, and the right hind leg was sham-treated. In Expt. 2, male C57BL6J mice were subcutaneously administered a vehicle (Veh group) or the estrogen receptor (ER) antagonist ICI 182,780 (ICI group) via an osmotic pump for 27 d, and each group was subsequently fed CON or GEN diets from day 3 to day 27. Muscle atrophy was induced on day 17 as in Expt. 1. In Expt. 3, male C57BL6J mice were subcutaneously administered vehicle or a selective ER agonist-ER-α [4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT)] or ER-ß [2,3-bis(4-hydroxyphenyl)-propionitrile (DPN)]-or genistein (GEN-sc-i) via an osmotic pump for 13 d, and muscle atrophy was induced on day 3 as in Expt. 1. The ratio of denervated soleus muscle weight to sham-operated soleus muscle weight (d/s ratio) was used as the index of muscle atrophy. RESULTS: Expt. 1: The d/s ratio in the GEN group was 20% higher than that in the CON group (P < 0.05). Expt. 2: The d/s ratio in the Veh-GEN group was 14% higher than that in the Veh-CON group (P < 0.05), although there was no significant difference between ICI-CON and ICI-GEN groups (P = 0.69). Expt. 3: The d/s ratio in the PPT-treated group was 20% greater than that in the Veh group (P < 0.05), but DPN and GEN-sc-i had no effect on the d/s ratio (P ≥ 0.05 compared with vehicle). CONCLUSION: Genistein intake mitigated denervation-induced soleus muscle atrophy. ER-α was related to the preventive effect of genistein on muscle atrophy.

Acupuncture plus low-frequency electrical stimulation (Acu-LFES) attenuates denervation-induced muscle atrophy.

Muscle wasting occurs in a variety of clinical situations, including denervation. There is no effective pharmacological treatment for muscle wasting. In this study, we used a tibial nerve denervation model to test acupuncture plus low-frequency electric stimulation (Acu-LFES) as a therapeutic strategy for muscle atrophy. Acupuncture needles were connected to an SDZ-II electronic acupuncture device delivering pulses at 20 Hz and 1 mA; the treatment was 15 min daily for 2 wk. Acu-LFES prevented soleus and plantaris muscle weight loss and increased muscle cross-sectional area in denervated mice. The abundances of Pax7, MyoD, myogenin, and embryonic myosin heavy chain were significantly increased by Acu-LFES in both normal and denervated muscle. The number of central nuclei was increased in Acu-LFES-treated muscle fibers. Phosphorylation of Akt was downregulated by denervation leading to a decline in muscle mass; however, Acu-LFES prevented the denervation-induced decline largely by upregulation of the IGF-1 signaling pathway. Acu-LFES reduced the abundance of muscle catabolic proteins forkhead O transcription factor and myostatin, contributing to the attenuated muscle atrophy. Acu-LFES stimulated the expression of macrophage markers (F4/80, IL-1b, and arginase-1) and inflammatory cytokines (IL-6, IFNγ, and TNFα) in normal and denervated muscle. Acu-LFES also stimulated production of the muscle-specific microRNAs miR-1 and miR-206. We conclude that Acu-LFES is effective in counteracting denervation-induced skeletal muscle atrophy and increasing muscle regeneration. Upregulation of IGF-1, downregulation of myostatin, and alteration of microRNAs contribute to the attenuation of muscle atrophy in denervated mice.

Selective peripheral denervation for the treatment of spasmodic torticollis: long-term follow-up results from 648 patients.

BACKGROUND: Selective peripheral denervation (SPD) is currently the primary surgical treatment for spasmodic torticollis (ST). Our objective here is to report on the outcome of patients treated with this procedure for ST in our department. METHODS: Between June 1995 and June 2013, 648 patients underwent SPD for ST. We included 293 women (45.2 %) and 355 men (54.8 %) with a mean age of 41.1 years (range, 8-74 years) at the onset of dystonia. Surgery was performed at a mean of 3.6 years (range, 1-32 years) after onset of symptoms. Data on clinical presentation, radiological studies, operation tragedy, clinical outcomes and complications were analysed retrospectively. For evaluation of clinical outcomes, patients' responses were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). RESULTS: Results were obtained from all 648 patients with a follow-up period ranging from 11 months to 154 months (mean, 33.4 months). The mean preoperative TWSTRS score was 54.7 ± 18.3 points (range, 39-67 points), which decreased to 31.1 ± 11.6 points postoperatively (range, 1-67 points); a significant improvement was observed between preoperative and postoperative TWSTRS evaluation; the clinical improvement of TWSTRS was 73.5 ± 11.9 %. In addition, no deaths and serious complications occurred in this cohort of patients. CONCLUSIONS: SPD is an effective surgical method for patients with ST. This procedure should be recommended if conservative therapy does not offer satisfactory relief of symptoms.

Breast reconstruction with the denervated latissimus dorsi musculocutaneous flap.

OBJECTIVE: To analyze clinical implications of the thoracodorsal nerve division in the latissimus dorsi musculocutaneous flap breast reconstruction. PATIENTS AND METHODS: Prospective cohort study was conducted on 29 patients. Breast reconstruction with latissimus dorsi musculocutaneous flap was performed unilaterally in 20 patients or bilaterally in 9 women (38 breasts). Thoracodorsal nerve was divided during reconstruction of 20 breasts (group 1) and was preserved for 18 breasts (group 2). Height, width, projection, area of the covering skin and volume of the reconstructed and healthy breasts were measured on the 3D images of the anterior chest wall, taken 6 weeks and 6 months postoperatively with the Di3D 3D camera. Data regarding tissue consistency, painfulness and animation of the reconstructed breast, symmetry of both breasts and overall satisfaction after the surgery were collected at 6 months. RESULTS: The reconstructed and healthy breasts decreased in volume in group 1 (-45.85 cm(3) ± 48.41 cm(3), p = 0.0004; -29.13 cm(3) ± 14.98 cm(3), p = 0.0009) and in group 2 (-31.5 cm(3) ± 25.35 cm(3), p = 0.0001; -15.4 cm(3) ± 21.96 cm(3), p = 0.0537). There were no differences in decrease in volume between groups 1 and 2 (p > 0.05). Respondents in group 1 in comparison to group 2 showed similar satisfaction of the tissue consistency of the reconstructed breast (p > 0.05) and the level of symmetry between both breasts (p > 0.05), gave lower scores for painfulness (p < 0.0001), animation (p < 0.0001) and higher scores for the overall satisfaction about the reconstructed breast (p = 0.0001). CONCLUSION: We suggest that division of the thoracodorsal nerve during latissimus dorsi musculocutaneous flap breast reconstruction is a useful undertaking to minimize unnatural animation of the reconstructed breast.

Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt.

Although it is well known that administration of the selective ß(2)-adrenergic agonist clenbuterol (CB) protects muscle following denervation (DEN), the underlying molecular mechanism remains unclear. We report that in vivo treatment with CB (3 mg/kg sc) for 3 days induces antiproteolytic effects in normal and denervated rat soleus muscle via distinct mechanisms. In normal soleus muscle, CB treatment stimulates protein synthesis, inhibits Ca(2+)-dependent proteolysis, and increases the levels of calpastatin protein. On the other hand, the administration of CB to DEN rats ameliorates the loss of muscle mass, enhances the rate of protein synthesis, attenuates hyperactivation of proteasomal and lysosomal proteolysis, and suppresses the transcription of the lysosomal protease cathepsin L and of atrogin-1/MAFbx and MuRF1, two ubiquitin (Ub) ligases involved in muscle atrophy. These effects were not associated with alterations in either IGF-I content or Akt phosphorylation levels. In isolated muscles, CB (10(-6) M) treatment significantly attenuated DEN-induced overall proteolysis and upregulation in the mRNA levels of the Ub ligases. Similar responses were observed in denervated muscles exposed to 6-BNZ-cAMP (500 µM), a PKA activator. The in vitro addition of triciribine (10 µM), a selective Akt inhibitor, did not block the inhibitory effects of CB on proteolysis and Ub ligase mRNA levels. These data indicate that short-term treatment with CB mitigates DEN-induced atrophy of the soleus muscle through the stimulation of protein synthesis, downregulation of cathepsin L and Ub ligases, and consequent inhibition of lysosomal and proteasomal activities and that these effects are independent of Akt and possibly mediated by the cAMP/PKA signaling pathway.

Double muscle innervation using end-to-side neurorrhaphy in rats.

CONTEXT AND OBJECTIVE: One of the techniques used for treating facial paralysis is double muscle innervation using end-to-end neurorrhaphy with sectioning of healthy nerves. The aim of this study was to evaluate whether double muscle innervation by means of end-to-side neurorrhaphy could occur, with maintenance of muscle innervation. DESIGN AND SETTING: Experimental study developed at the Experimental Research Center, Faculdade de Medicina de Botucatu, Unesp. METHODS: One hundred rats were allocated to five groups as follows: G1, control group; G2, the peroneal nerve was sectioned; G3, the tibial nerve was transected and the proximal stump was end-to-side sutured to the intact peroneal nerve; G4, 120 days after the G3 surgery, the peroneal nerve was sectioned proximally to the neurorrhaphy; G5, 120 days after the G3 surgery, the peroneal and tibial nerves were sectioned proximally to the neurorrhaphy. RESULTS: One hundred and fifty days after the surgery, G3 did not show any change in tibial muscle weight or muscle fiber diameter, but the axonal fiber diameter in the peroneal nerve distal to the neurorrhaphy had decreased. Although G4 showed atrophy of the cranial tibial muscle 30 days after sectioning the peroneal nerve, the electrophysiological test results and axonal diameter measurement confirmed that muscle reinnervation had occurred. CONCLUSION: These findings suggest that double muscle innervation did not occur through end-to-side neurorrhaphy; the tibial nerve was not able to maintain muscle innervation after the peroneal nerve had been sectioned, although muscle reinnervation was found to have occurred, 30 days after the peroneal nerve had been sectioned.

Double muscle innervation using end-to-side neurorrhaphy in rats / Dupla inervação muscular com neurorrafia término-lateral em ratos

CONTEXT AND OBJECTIVE: One of the techniques used for treating facial paralysis is double muscle innervation using end-to-end neurorrhaphy with sectioning of healthy nerves. The aim of this study was to evaluate whether double muscle innervation by means of end-to-side neurorrhaphy could occur, with maintenance of muscle innervation. DESIGN AND SETTING: Experimental study developed at the Experimental Research Center, Faculdade de Medicina de Botucatu, Unesp. METHODS: One hundred rats were allocated to five groups as follows: G1, control group; G2, the peroneal nerve was sectioned; G3, the tibial nerve was transected and the proximal stump was end-to-side sutured to the intact peroneal nerve; G4, 120 days after the G3 surgery, the peroneal nerve was sectioned proximally to the neurorrhaphy; G5, 120 days after the G3 surgery, the peroneal and tibial nerves were sectioned proximally to the neurorrhaphy. RESULTS: One hundred and fifty days after the surgery, G3 did not show any change in tibial muscle weight or muscle fiber diameter, but the axonal fiber diameter in the peroneal nerve distal to the neurorrhaphy had decreased. Although G4 showed atrophy of the cranial tibial muscle 30 days after sectioning the peroneal nerve, the electrophysiological test results and axonal diameter measurement confirmed that muscle reinnervation had occurred. CONCLUSION: These findings suggest that double muscle innervation did not occur through end-to-side neurorrhaphy; the tibial nerve was not able to maintain muscle innervation after the peroneal nerve had been sectioned, although muscle reinnervation was found to have occurred, 30 days after the peroneal nerve had been sectioned.

CONTEXTO E OBJETIVO: Uma das técnicas utilizadas para tratamento da paralisia facial é a dupla inervação muscular com neurorrafia término-terminal, seccionando-se nervos sadios. O objetivo deste trabalho foi avaliar a ocorrência de dupla inervação muscular através de neurorrafia término-lateral e a manutenção da inervação. TIPO DE ESTUDO E LOCAL: Estudo experimental desenvolvido no Centro de Pesquisa Experimental da Faculdade de Medicina de Botucatu, Unesp. MÉTODOS: Cem ratos foram distribuídos em cinco grupos: G1, controle; G2, secção do nervo fibular; G3, o nervo tibial foi seccionado e o coto proximal suturado na lateral do nervo fibular íntegro; G4, 120 dias após a cirurgia do G3, o nervo fibular foi seccionado proximal à neurorrafia; G5, 120 dias após a cirurgia do G3, os nervos fibular e tibial foram seccionados proximal à neurorrafia. RESULTADOS: Após 150 dias da cirurgia, não foi observada variação na massa do músculo tibial ou no diâmetro das fibras musculares no G3, porém, houve redução do diâmetro da fibra axonal do nervo fibular distal à neurorrafia. Embora, no G4, tenha ocorrido atrofia do músculo tibial cranial 30 dias após a secção do nervo fibular, os resultados do teste eletrofisiológico e da medida do diâmetro axonal confirmaram a ocorrência de reinervação muscular. CONCLUSÃO: Estes resultados sugerem que a dupla inervação muscular não ocorreu através da neurorrafia término-lateral; o nervo tibial não foi capaz de manter a inervação muscular após a secção do nervo fibular; contudo, ocorreu reinervação muscular 30 dias após a secção do nervo fibular.

Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice.

Skeletal muscle wasting is a major human morbidity, and contributes to mortality in a variety of clinical settings, including denervation and cancer cachexia. In this study, we demonstrate that the expression level and autoubiquitination of tumor necrosis factor (α) receptor adaptor protein 6 (TRAF6), a protein involved in receptor-mediated activation of several signaling pathways, is enhanced in skeletal muscle during atrophy. Skeletal muscle-restricted depletion of TRAF6 rescues myofibril degradation and preserves muscle fiber size and strength upon denervation. TRAF6 mediates the activation of JNK1/2, p38 mitogen-activated protein kinase, adenosine monophosphate-activated protein kinase, and nuclear factor κB, and induces the expression of muscle-specific E3 ubiquitin ligases and autophagy-related molecules in skeletal muscle upon denervation. Inhibition of TRAF6 also preserves the orderly pattern of intermyofibrillar and subsarcolemmal mitochondria in denervated muscle. Moreover, depletion of TRAF6 prevents cancer cachexia in an experimental mouse model. This study unveils a novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an important therapeutic target to prevent skeletal muscle wasting.

Embryonic stem cell-derived motor neurons form neuromuscular junctions in vitro and enhance motor functional recovery in vivo.

BACKGROUND: Transplantation of embryonic stem cell-derived motor neurons may support the biological integrity of denervated muscle by forming new neuromuscular junctions and up-regulating specific growth factors. The authors examined the functional properties of embryonic stem cell-derived motor neurons in vitro and the effect of these cells transplanted in vivo. METHODS: Murine GFP/HB9 embryonic stem cells were differentiated into motor neurons. Co-cultures of motor neurons and myotubes were prepared to confirm the formation of neuromuscular junctions with synaptic markers. Athymic mice (n = 59) were assigned randomly to one of three experimental groups. A tibial nerve transection was performed without nerve repair, and motor neurons were transplanted into the gastrocnemius muscles immediately after transection (n = 24) or 3 weeks after denervation (n = 24). Quantitative and histologic assessments of gastrocnemius muscle were performed at days 7 and 21 after cell transplantation. Additional experimental groups (n = 11), where the tibial nerve underwent repair after transplantation, were formed. The effect of the transplants on motor recovery following nerve repair was investigated. RESULTS: Co-culture experiments showed the formation of neuromuscular junctions. In the experiment with nerve transection without nerve repair, the muscles transplanted with motor neurons were less atrophied than control phosphate-buffered saline-injected muscles at days 7 and 21. Those muscles receiving cells transplanted 3 weeks after denervation were not preserved. The motor recovery after nerve repair with cell transplantation was significantly enhanced compared with the control group. CONCLUSIONS: Transplantation of motor neurons prevented denervation atrophy but was not capable of rescuing already atrophied muscle. After nerve repair, motor neuron transplantation improved functional recovery.

Effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass graft surgery.

OBJECTIVE: To evaluate the effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass surgery. METHODS: Between September and November, 50 patients without history or previous diagnosis of atrial arrhythmia from the same institution presenting coronary heart disease with indication for coronary artery graft bypass surgery were enrolled in a prospective and randomized study. The exclusion criteria were: patients older than 75 years of age, previous history of atrial arrhythmia and associated heart surgeries. Denervation was performed before cardiopulmonary bypass and it was achieved by removing the adipose tissues around the superior vena cava, aorta and pulmonary artery. The groups were compared regarding demographic, clinical and operative variables. RESULTS: There were no hospital mortalities. The additional time for the denervation was 7.64+/-2.33 minutes, and there were no associated complications. Postoperative atrial fibrillation was present in two (8%) patients of the Control Group and in three (12%) patients who underwent ventral cardiac denervation. The risk of postoperative atrial fibrillation in patients undergoing ventral cardiac denervation was 22% higher than in the Control Group (0.56-2.66,confidence interval); however, this outcome was not statistically significant (p=0.64). CONCLUSION: Ventral cardiac denervation, despite being a fast and low-risk procedure, does not significantly reduce the incidence of atrial fibrillation after coronary artery bypass graft surgery.

Efeito da denervação cardíaca ventral na incidência de fibrilação atrial após revascularização cirúrgica do miocárdio / Effect of ventral cardiac denervation in the incidence of atrial fibrilation after coronary artery bypass graft surgery

OBJETIVO: Verificar o efeito da denervação cardíaca ventral na incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio. MÉTODOS: Entre setembro e novembro de 2005, 50 pacientes consecutivos da mesma instituição foram alocados neste estudo prospectivo e randomizado. Foram selecionados pacientes portadores de insuficiência coronariana com indicação de revascularização cirúrgica do miocárdio, sem história ou diagnóstico prévio de arritmia atrial. Os critérios de exclusão foram: idade acima de 75 anos, história prévia de arritmia atrial e operações cardíacas associadas. A denervação era realizada antes do início da circulação extracorpórea pela remoção do tecido gorduroso ao redor da veia cava superior, aorta e artéria pulmonar. Os grupos foram comparados de acordo com as características clínicas, demográficas e variáveis operatórias. RESULTADOS: Não houve mortalidade hospitalar em ambos os grupos. O tempo médio adicional para realização da denervação foi de 7,64 + 2,33 minutos e não houve complicações associadas ao procedimento. Cinco pacientes apresentaram fibrilação atrial no pós-operatório, sendo dois (8 por cento) no grupo controle e três (12 por cento) no grupo denervação. O risco dos pacientes do grupo denervação apresentarem fibrilação atrial foi 22 por cento maior do que no grupo controle (intervalo de confiança, 0,56-2,66), porém, este resultado não foi estatisticamente significativo (p=0,64). CONCLUSÕES: A denervação cardíaca ventral, apesar de rápida execução e de baixo risco, não apresentou efeito na redução da incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio.

OBJECTIVE: To evaluate the effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass surgery. METHODS: Between September and November, 50 patients without history or previous diagnosis of atrial arrhythmia from the same institution presenting coronary heart disease with indication for coronary artery graft bypass surgery were enrolled in a prospective and randomized study. The exclusion criteria were: patients older than 75 years of age, previous history of atrial arrhythmia and associated heart surgeries. Denervation was performed before cardiopulmonary bypass and it was achieved by removing the adipose tissues around the superior vena cava, aorta and pulmonary artery. The groups were compared regarding demographic, clinical and operative variables. RESULTS: There were no hospital mortalities. The additional time for the denervation was 7.64±2.33 minutes, and there were no associated complications. Postoperative atrial fibrillation was present in two (8 percent) patients of the Control Group and in three (12 percent) patients who underwent ventral cardiac denervation. The risk of postoperative atrial fibrillation in patients undergoing ventral cardiac denervation was 22 percent higher than in the Control Group (0.56-2.66,confidence interval); however, this outcome was not statistically significant (p=0.64). CONCLUSION: Ventral cardiac denervation, despite being a fast and low-risk procedure, does not significantly reduce the incidence of atrial fibrillation after coronary artery bypass graft surgery.

Electromyographic findings after different selective neck dissections.

OBJECTIVES: The objective was to compare electrophysiologic investigations of the upper trapezius muscle (UT) after different selective neck dissections (SND) and analyze the differences between types of SND and the preservation and excision of the cervical nerves (the C2-4 rami of the cervical plexus). STUDY DESIGN: Retrospective study of 54 patients (average age, 65.1 +/- 9.6 yr, 45 males) with 70 SND. METHODS: Patients underwent needle electromyography (EMG) of the UT by 4 months after surgery. The findings were rated according to the 5 point EMG scale system from 1 (total denervation: positive sharp wave or fibrillation potential at rest and electrical silence at voluntary contraction) to 5 (normal pattern). RESULTS: The average EMG scale was 1.7 +/- 1.1, 58.6% for score 1 and only 5.7% for score 5. There was not a significant difference in the EMG scale between the types of SND, whereas the group in which the cervical nerves were excised was significantly lower than in that in which it was preserved. The average EMG scales in the former and latter were 1.5 +/- 0.8 and 2.0 +/- 1.3, 68.8%. CONCLUSIONS: The study data confirm that complete or incomplete denervation of the UT was caused by axonal injury of the spinal accessory nerve, even though it was spared, because of traction of the nerve during neck dissection. Second, the excision of the C2 to 4 rami of the cervical plexus caused worse damage of the UT. It is suggested that it is important to preserve the cervical nerves to avoid denervation of the UT.

Effect of periurethral denervation on smooth muscles of the lower urinary tract.

OBJECTIVE: This study was undertaken to determine the effect of periurethral denervation on contractile function of the smooth muscle of the lower urinary tract of the female rat. STUDY DESIGN: Periurethral nerve transection or sham operation was performed in 35 young female rats. Contractile function of the bladder dome and base was determined as a function of time after surgery. Statistical analysis was conducted by Student t test. RESULTS: Periurethral denervation resulted in impaired contractile responses to electrical field stimulation in the bladder base (nerve-transected 45 +/- 11 g/cm 2 ; sham 84 +/- 10 g/cm 2 , P < .05) and dome (nerve-transected 179 +/- 16 g/cm 2 ; sham 334 +/- 29 g/cm 2 , P < .05) 2 weeks after nerve transection. The ability to respond to potassium chloride and the muscarinic agonist, carbachol, and the rates of contraction and relaxation, however, remained intact. Baseline phasic contractile activity was increased significantly in bladders from nerve-transected animals. Maximal field-stimulated contractions of the longitudinal urethra smooth muscle were not altered by periurethral denervation (sham 21 +/- 6 g/cm 2 , nerve-transected 19 +/- 5 g/cm 2 , P = .4). Compromised nerve-mediated contractions of the bladder dome and base improved significantly by 21 days. CONCLUSION: Periurethral nerve transection results in transient impairment of neurogenic contractile responses in the bladder base and dome, though the intrinsic ability of the bladder to contract remains intact. This compromised response of the dome, in conjunction with previous results demonstrating impaired urethral smooth muscle relaxation, suggests that transection of periurethral neurons may have complex effects on the entire lower urinary tract.

Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration?

Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES, and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 +/- 14.8 SD (p < 0.0001 vs DDM 14.9 +/- 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 +/- 5.7 SD (p < 0.0001 vs DDM 25.7 +/- 23.7 SD); the mean percentile fat area is 2.1 +/- 2.4 SD (p < 0.001 vs DDM 12.8 +/- 12.1 SD); and the mean percentile connective tissue area is 3.6 +/- 4.6 SD (p < 0.001 vs DDM 61.6 +/- 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter smaller than 10 microm, while the FES-trained subjects have more that 50% of myofibers larger than 30 microm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.

Correlation between inter-vertebral disc morphology and the results in patients undergoing Graf ligament stabilisation.

BACKGROUND: Previous studies have shown Graf ligament stabilisation procedure to give mixed results in the short to medium term. The aim of this study was to correlate the pre-operative state of the disc, multifidus muscles, age of the patient, levels operated and the clinical outcome after a mean follow-up of 47 months. METHODS: Graf ligament stabilisation procedure was carried out in 38 patients between 1996 and 1999. Their post-operative status was assessed using MacNab criteria. The post-operative follow-up was by postal questionnaires and review of the clinical notes. Disc morphology and multifidus muscle wasting was graded blindly and independently. The intra- and interobserver reliability was measured with kappa score and classified using the kappa classification of Landis and Koch. Correlation was measured with the help of Spearman correlation coefficient. RESULTS: Thirty-eight patients (100%) returned the questionnaires. Mean follow-up time was 47.55 months. Fifty-nine levels were operated on. Mean age was 39.68 years. The overall re-operation rate was 15.8%. The intra- and interobserver reliability was graded as good to substantial. Twenty-two patients (57.89%) were satisfied with the procedure. There was no statistically significant correlation between disc morphology, multifidus muscle wasting, sex, age, number of levels operated, the levels operated, and the satisfaction rate. CONCLUSIONS: The indications of Graf ligament stabilisation procedure are not clear. Further work is necessary to clearly identify the indication for the procedure.