Altered defaecatory behaviour and faecal incontinence in a video-tracked animal model of pudendal neuropathy.

AIM: The aim was to develop a behavioural animal model of faecal continence and assess the effect of retro-uterine balloon inflation (RBI) injury. RBI in the rat causes pudendal neuropathy, a risk factor for obstetric related faecal incontinence in humans. METHOD: Video-tracking of healthy rats (n = 12) in a cage containing a latrine box was used to monitor their defaecatory behaviour index (DBI) over 2 weeks. The DBI (range 0-1) was devised by dividing the defaecation rate (pellets per hour) outside the latrine by that of the whole cage. A score of 0 indicates all pellets were deposited in the latrine. Subsequently, the effects of RBI (n = 19), sham surgery (n = 4) and colostomy (n = 2) were determined by monitoring the DBI for 2 weeks preoperatively and 3 weeks postoperatively. RESULTS: The DBI for healthy rats was 0.1 ± 0.03 with no significant change over 2 weeks (P = 0.71). In the RBI group, 13 of 19 rats (68%) showed no significant change in DBI postoperatively (0.08 ±  -0.05 vs 0.11 ±  -0.07) while in six rats the DBI increased from 0.16 ±  -0.09 to 0.46 ± 0.23. The negative control, sham surgery, did not significantly affect the DBI (0.09 ± 0.06 vs 0.08 ± 0.04, P = 0.14). The positive control, colostomy, increased the DBI from 0.26 ± 0.03 to 0.86 ± 0.08. CONCLUSIONS: This is the first study showing a quantifiable change in defaecatory behaviour following injury in an animal model. This model of pudendal neuropathy affects continence in 32% of rats and provides a basis for research on interventions for incontinence.

The role of 3D printing in preoperative planning for heart transplantation in complex congenital heart disease.

BACKGROUND: The presence of a structural cardiac defect in the setting of dextrocardia is extremely rare. Graspable models allow enhanced appreciation of aberrant structures and vascular relations, particularly in rare and complex cases. This is the first case report of the use of a replica of a patients' anatomy to plan the surgical strategy in the setting of dextrocardia. AIMS: We intend to demonstrate the benefit of three-dimensional printing to enhance preoperative planning in complex congenital heart disease undergoing heart transplantation. The anomalous structures encountered include situs inversus dextrocardia, transposition of the great vessels, a single atrium and a dilated double-outlet single right ventricle. METHODS: Computed Tomography acquisition was performed with the use of ECG multiphase gating technology and contrast enhancement. The structures of interest were segmented and the generated 3D mesh was exported as a stereolithographic (STL) file. The model was printed on a Z-Corp 250 binder jetting printer. Post processing techniques were used to enhance model strength. RESULTS: Pre-operative 3D visualisation of the patients' anatomy allowed for a more comprehensive surgical strategy to be planned, thus reducing the intra-operative duration and cross-clamp time which are recognised to correlate with reduced patient morbidity. CONCLUSION: The ongoing advances in medical image procurement and 3D processing software and printing technology will continue to enhance preoperative planning and thereby improve patient care. We demonstrate the pivotal role played by such technologies in advancing spatial comprehension of complex aberrant anatomy.

Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence.

BACKGROUND: Sacral neuromodulation (SNM) is a treatment option for intractable fecal incontinence. The mechanism of action is unclear, however, increasing evidence for afferent somatosensory effects exists. This study's aim was to elucidate effects of acute SNM on the cerebral cortex in a rodent model of pudendal nerve injury. METHODS: The effects of 14 Hz and 2 Hz SNM on sensory cortical activation were studied. In 32 anesthetized rats, anal canal evoked potentials (EPs) were recorded over the primary somatosensory cortex. Pudendal nerve injury was produced by 1-hour inflation of two intra-pelvic balloons. Four groups were studied: balloon injury, balloon injury plus either 14 Hz or 2 Hz SNM, sham operation. Immunohistochemistry for the neural plasticity marker polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells (numerical density and location) in the somatosensory cortex was performed. KEY RESULTS: Anal EP amplitudes diminished during balloon inflation; 14 Hz SNM restored diminished anal EPs to initial levels and 2 Hz SNM to above initial levels. Evoked potential latencies were prolonged during balloon inflation. The numerical density of PSA-NCAM positive cells increased in the SNM groups, but not in sham or balloon injury without SNM. Stimulated cortices showed clusters of PSA-NCAM positive cells in layers II, IV, and V. Post SNM changes were similar in both SNM groups. CONCLUSIONS & INFERENCES: Sacral neuromodulation augments anal representation in the sensory cortex and restores afferent pathways following injury. PSA-NCAM positive cell density is increased in stimulated cortices and positive cells are clustered in layers II, IV, and V.

Acute lumbosacral nerve stimulation does not affect anorectal motor function in a rodent model.

BACKGROUND: Sacral nerve stimulation has become a first line treatment for fecal incontinence, however, its effect on the motor function of the anorectum is uncertain. The aim of this study was to apply acute lumbosacral nerve stimulation in an animal model and to determine its effect on the external and internal anal sphincter forces, the rectoanal inhibitory and excitatory reflexes, and the slow wave frequency of the internal anal sphincter. METHODS: Lumbosacral nerve stimulation was applied to 16 nulliparous female rats. A novel in vivo preparation was designed to allow simultaneous monitoring of external and internal anal sphincter forces. The effect of rectal distension on the two anal sphincters was also studied. KEY RESULTS: Lumbosacral nerve stimulation delivered at either S1 or L6 in rodents did not affect sphincter forces, rectoanal reflexes or slow wave frequency of anal canal smooth muscle. CONCLUSIONS & INFERENCES: The absence of effect on the motor pathways of continence suggests that the mechanism of action is predominantly on sensory feedback mechanisms from the anorectum, thereby increasing cortical awareness of the pelvic floor.

Mechanically evoked cortical potentials: A physiological approach to assessment of anorectal sensory pathways.

BACKGROUND: Normal defaecation involves activation of anorectal mechanoreceptors responsive to pressure and stretch. The aim of this study was to develop selective anal and rectal mucosal light-touch stimulation suitable for measurement of cortical evoked potentials (EPs) in order to explore the sensory arm of these pathways. NEW METHOD: A novel device was manufactured to deliver selective rectal and/or anal light-touch stimulation using a shielded inter-dental brush mounted on a rotating stepper motor (1Hz, 1ms, 15° rotation). Resultant somatosensory EPs recorded with a 32-channel cortical multi-electrode array were compared to those elicited by electrical anorectal stimulation (2mm anal plug electrode [1Hz, 1ms, 10V]). RESULTS: Eighteen anaesthetized female Wistar rats (body mass 180-250g) were studied. Electrical and mechanical stimulation provoked similar maximal response amplitudes (electrical anorectal 39.0µV[SEM 5.5], mechanical anal 42.2µV[8.1], mechanical rectal 45.8µV[9.0]). Response latency was longer following mechanical stimulation (electrical anorectal 8.8ms[0.5], mechanical anal 16.4ms[1.1], mechanical rectal 18.3ms[2.5]). The extent of activated sensory cortex was smaller for mechanical stimulation. Sensory inferior rectal nerve activity was greater during anal compared to rectal mechanical in a subgroup of 4 rats. Evoked potentials were reproducible over 40min in a subgroup of 9 rats. COMPARISON WITH EXISTING METHODS: Cortical EPs are typically recorded in response to non-physiological electrical stimuli. The use of a mechanical stimulus may provide a more localized physiological method of assessment. CONCLUSIONS: To the authors' knowledge these are the first selective brush-elicited anal and rectal EPs recorded in animals and provide a physiological approach to testing of anorectal afferent pathways.

A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation.

BACKGROUND: Sacral nerve stimulation (SNS) is now well established as a treatment for fecal incontinence (FI) resistant to conservative measures and may also have utility in the management of chronic constipation; however, mechanism of action is not fully understood. End organ effects of SNS have been studied in both clinical and experimental settings, but interpretation is difficult due to the multitude of techniques used and heterogeneity of reported findings. The aim of this study was to systematically review available evidence on the mechanisms of SNS in the treatment of FI and constipation. METHODS: Two systematic reviews of the literature (performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses framework) were performed to identify manuscripts pertaining to (a) clinical and (b) physiological effects of SNS during the management of hindgut dysfunction. KEY RESULTS: The clinical literature search revealed 161 articles, of which 53 were deemed suitable for analysis. The experimental literature search revealed 43 articles, of which nine were deemed suitable for analysis. These studies reported results of investigative techniques examining changes in cortical, gastrointestinal, colonic, rectal, and anal function. CONCLUSIONS & INFERENCES: The initial hypothesis that the mechanism of SNS was primarily peripheral motor neurostimulation is not supported by the majority of recent studies. Due to the large body of evidence demonstrating effects outside of the anorectum, it appears likely that the influence of SNS on anorectal function occurs at a pelvic afferent or central level.

Effects of stimulation frequency and intensity in sacral neuromodulation on anorectal inputs to the somatosensory cortex in an experimental model.

INTRODUCTION: Although sacral neuromodulation (SNM) is an established treatment for faecal incontinence, stimulation parameters have been derived empirically and only one frequency (14 Hz) is employed clinically. The aim of this study was to test a range of stimulation frequencies to establish an optimal frequency of SNM for maximum augmentation of anal canal cortical evoked potentials (EPs) in an animal model. METHODS: In female Wistar rats, anal canal EPs were recorded over the primary somatosensory cortex using a flexible multielectrode array, and the effect of SNM was studied. SNM was applied at 0·1-100 Hz and a frequency response curve plotted. The data were fitted to a quadratic equation. RESULTS: The magnitude of potentiation of anal canal EPs caused by SNM depended significantly on stimulation frequency (P < 0·001). The frequency-potentiation relationship was parabolic in form, with a clear optimum at 2 Hz. The SNM must be applied for at least 3 min. The theoretical maximal potentiation predicted by the model was not found to be statistically different to actual data recorded (P = 0·514-0·814). The response depended on stimulation amplitude in an 'all-or-nothing' fashion. EPs were augmented when the SNM intensity was 0·5 times the motor threshold to tail twitch or greater, but values below this intensity failed to affect the EPs. CONCLUSION: The effect of SNM in this animal model is governed principally by frequency, with an optimum of 2 Hz. If animal data can be translated to humans, optimization of SNM frequency may offer a clinically relevant improvement in the efficacy of SNM. Surgical relevance Sacral neuromodulation (SNM) for faecal incontinence currently employs stimulation parameters that have been derived empirically and may not be optimal. This study used an animal model of SNM and focused on its acute effect on anal canal cortical evoked potentials (EPs). It was found that SNM potentiated EPs, with a clear optimum at a frequency of 2 Hz. If this finding is applicable to the mechanism of action of human SNM, this suggests that there may be a clinically relevant improvement by reducing stimulus frequency from its typical value of 14 Hz to 2 Hz.

Behavioural studies of faecal continence in the rat.

BACKGROUND: A behavioural animal model of faecal continence and/or incontinence would be of value in experimental studies of the mechanisms by which sacral neuromodulation can effect continence mechanisms in humans. AIM: The aim of this behavioural study was to establish whether the rat, an obligate coprophagic species, exhibits patterns of faecal continence. METHODS: Standard rat cages were modified to consist of a food and drink area, a nesting area and an empty latrine area. Three floor pressure pads were connected to hour meters to record the time spent in each area over the course of 4 days. The door to the latrine was open for 2 days and closed for another 2 days to create a physical barrier that could only be surmounted by climbing over a partition. RESULTS: In the first 2 days, most faecal pellets (74 ± 20 %; p < 0.0001) were deposited in the latrine and this was not changed by door closure (81 ± 13 %). Door closure had no effect per se on pellet output (p = 0.99), nor did it alter the place preference for defaecation (p = 0.17, two factor ANOVA). Rats spent less time in the latrine area accounting for 23 and 13 % of total time before and after the door was closed, respectively. Normal and infrared videography showed that the place preference for pellets was not due to pellet collection for coprophagic purposes. CONCLUSIONS: The rat demonstrates place preference for defaecation and may drop pellets to mark remote boundaries. This simple method may prove useful in future animal studies of neuropathic faecal incontinence and refinement of neuromodulation interventions that lack placebo effects.

Is there a nitrergic modulation of the rat external anal sphincter?

Nitric oxide is known to relax the internal anal sphincter, but its effect on the external anal sphincter (EAS) is unknown. The aim of this study was to investigate whether there is a nitrergic nerve plexus that modulates the EAS, similar to that found in oesophageal striated muscle. An in vitro ring preparation of rat anal canal was used to evaluate the effects of the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine (L-NNA) and the NO donor sodium nitroprusside (SNP) on the EAS in conditions of neuromuscular blockade and the effect of SNP on nerve-evoked contractions. Immunohistological experiments were conducted to determine whether the neuronal isoform of nitric oxide synthase (nNOS) is present in the EAS. During direct muscle stimulation neither L-NNA (P = 0.32) nor SNP (P = 0.19) significantly changed the EF(50), which is the frequency at which 50% of maximal contraction is reached, compared with a time-dependent control. Nerve-evoked contractions were also not altered by addition of SNP to the tissue bath. Immunohistohistological experiments clearly showed co-localization of nNOS-positive nerve fibres at motor endplates of the oesophagus but not in the EAS. The internal anal sphincter was richly innervated by nitrergic fibres, but these did not extend into the EAS. In conclusion, there are no nitrergic motor fibres innervating the EAS, neurotransmission at the motor endplates is not affected by NO, and NO does not affect muscle force directly in conditions of neuromuscular blockade. There is, therefore, no evidence that EAS contraction is directly modulated by NO or by pudendal nitrergic fibres or diffusion from neighbouring nitrergic plexuses of the anal canal.

Upper airway dilator muscle weakness following intermittent and sustained hypoxia in the rat: effects of a superoxide scavenger.

Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may have considerable therapeutic value. We examined the effects of acute exposure to sustained and intermittent hypoxia on rat pharyngeal dilator muscle function. Additionally, we sought to test the efficacy of antioxidant treatment in ameliorating or preventing hypoxia-related muscle dysfunction. Isometric contractile and endurance properties of isolated rat sternohyoid muscle bundles were examined at 35 °C in vitro. Muscle bundles were exposed to one of four gas treatments: hyperoxia (control), sustained hypoxia (SH), intermittent hypoxia (IH) or hypoxia/re-oxygenation (HR), in the absence or presence of the superoxide scavenger--Tempol (10 mM). Stress-frequency relationship was determined in response to electrical stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Muscle performance was also assessed during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2.5 min). Compared to control, IH and HR treatments significantly decreased sternohyoid muscle force. The negative inotropic effect of the two gas protocols was similar, but both were of lesser magnitude than the effects of SH. SH, but not IH and HR, increased muscle fatigue. Tempol significantly increased sensitivity to stimulation in all muscle preparations and caused a leftward shift in the stress-frequency relationship of IH and SH treated muscles. Tempol did not ameliorate sternohyoid muscle fatigue during SH. We conclude that Tempol increases upper airway muscle sensitivity to stimulation but only modestly ameliorates respiratory muscle weakness during intermittent and sustained hypoxic conditions in vitro. Respiratory muscle fatigue during sustained hypoxia appears unrelated to oxidative stress.

Comparison of the motor discharge to the voluntary sphincters of continence in the rat.

BACKGROUND: The rat external anal sphincter (EAS) and external urethral sphincter (EUS) are voluntary muscles of continence that can display similar synchronous electromyographic (EMG) activity patterns. However, the two sphincters are quite different in structure and function. The EUS is a fast twitch muscle and contains fibers expressing type 2B myosin. In contrast, the EAS exhibits slower kinetics and lacks type 2B fibers. This striking contrast in kinetics and fiber type profiles may be shaped by differences in the basal motor drive that each sphincter receives. METHODS: A double EMG approach was used to obtain spontaneously active single motor unit action potentials from the EUS and EAS simultaneously and compare their basal discharge frequencies in urethane anaesthetized rats. KEY RESULTS: The basal firing rates of motor units of the EUS and EAS were not significantly different (3.9 ± 0.9 Hz vs. 3.1 ± 1.6 Hz, respectively, n = 7 animals, P = 0.32, paired Student's t-test). However, auto-correlogram analysis showed that EUS is driven by neurons with faster instantaneous firing frequencies: 30.5 ± 2.4 Hz vs 14.3 ± 0.9 Hz in the EAS (P = 0.03, paired Student's t-test). CONCLUSIONS & INFERENCES: The oscillator(s) driving the EUS operate(s) at a frequency twice that of the EAS. This may explain the presence of type 2B fibers in the EUS. In the inter-micturition periods no cross correlation was found in motor discharge to the sphincters suggesting that the two muscles do not share a common central drive to sustain the continent tonus of the two outlet tracts.

Combined ischemic and neuropathic insult to the anal canal in an animal model of obstetric-related trauma.

BACKGROUND: Childbirth, in particular, when it involves instrumental vaginal delivery, can result in direct trauma to the external anal sphincter muscle. In addition, a global injury to the pelvic floor, including neurovascular injury to the anal sphincter complex, may occur. OBJECTIVE: The aims of this study were to determine whether sensory drive from the anal canal and oxygenation of the external anal sphincter were compromised during simulated labor in a validated animal model of obstetric trauma. DESIGN: Fifteen female Wister rats were operated on. Group 1 (n = 5) underwent pelvic balloon compression for 1 hour to simulate increased pelvic pressure during childbirth. Somatosensory cortical potentials, evoked by electrically stimulating the anal canal, were tracked. In group 2 (sham), the balloons were not inflated. In group 3, tissue PO2 values of the external anal sphincter and femoral arterial blood flow were measured simultaneously during the period of balloon inflation. RESULTS: The peak amplitude of cortical evoked potentials was reduced (from 11.8 ± 1.5 µV to 3.1 ± 1.1 µV) during pelvic compression (p = 0.002, ANOVA). During this period, arterial blood flow to the hindlimb and the external anal sphincter tissue PO2 decreased by 20% (p < 0.001) and 60% (p < 0.001). CONCLUSION: Pelvic compression that mimics obstetric trauma is associated with diminished anocortical drive. This neural insult may be compounded by concomitant ischemia of the external anal sphincter.

Sacral nerve stimulation increases activation of the primary somatosensory cortex by anal canal stimulation in an experimental model.

BACKGROUND: Sacral and posterior tibial nerve stimulation may be used to treat faecal incontinence; however, the mechanism of action is unknown. The aim of this study was to establish whether sensory activation of the cerebral cortex by anal canal stimulation was increased by peripheral neuromodulation. METHODS: A multielectrode array was positioned over the right primary somatosensory cortex of anaesthetized rats. A brief burst of electrical stimulation was applied to either the left sacral root or the left posterior tibial nerve, and evoked potentials from anal canal stimulation were signal-averaged at intervals over 1 h. At the end of the experiment, the cerebral cortex was removed and probed for polysialylated neural cell adhesion molecule (PSA-NCAM). RESULTS: Sacral nerve root and posterior tibial nerve stimulation significantly increased the peak amplitude of primary cortical evoked potentials by 54.0 and 45.1 per cent respectively. This change persisted throughout the period of observation. The density of PSA-NCAM-positive cells in the somatosensory cortex underlying the electrode array was increased by approximately 50 per cent in the sacral nerve-stimulated group. CONCLUSION: Brief sacral neuromodulation induces profound changes in anal canal representation on the primary somatosensory cortex, providing a plausible hypothesis concerning the mechanism of action of neuromodulation in the treatment of faecal incontinence.

Effect of injury on S1 dorsal root ganglia in an experimental model of neuropathic faecal incontinence.

BACKGROUND: An experimental model of neuropathic faecal incontinence has recently been established. This study aimed to quantify and compare the effect of crush and compression injury on first-order sensory neurones of the inferior rectal nerve (IRN) using a nuclear marker of axonal injury, activating transcription factor (ATF) 3. METHODS: Eighteen Wistar rats were allocated to three groups: an unoperated control group, an IRN crush group (positive control) and a retrouterine balloon compression group. Five days after surgery, all animals were anaesthetized and perfused with fixative, and S1 dorsal root ganglia (DRG) were harvested. The tissue was sampled and neuronal nuclear ATF-3 expression calculated. RESULTS: Estimated total S1 DRG ATF-3 nuclear labelling was higher in the nerve crush (median (interquartile range) 171 (60-824) cells) and balloon compression (59 (20-274) cells) groups, compared with that in the unoperated control group (9 (3-24) cells) (P = 0.001 and P = 0.008 respectively). In all groups, most neurones displaying the marker of injury were of the C-fibre class. CONCLUSION: This study confirmed the presence of axonal injury in a pelvic compression model of obstetric injury. C-fibre afferent pathways appeared to be most vulnerable. Neuromodulation may function through augmentation of residual C-fibre pathways.

Chronic hypoxia increases rat diaphragm muscle endurance and sodium-potassium ATPase pump content.

The effects of chronic hypoxia (CH) on respiratory muscle are poorly understood. The aim of the present study was to examine the effects of CH on respiratory muscle structure and function, and to determine whether nitric oxide is implicated in respiratory muscle adaptation to CH. Male Wistar rats were exposed to CH for 1-6 weeks. Sternohyoid and diaphragm muscle contractile properties, muscle fibre type and size, the density of fibres expressing sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2 and sodium-potassium ATPase (Na+,K+-ATPase) pump content were determined. Muscle succinate dehydrogenase (SDH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) dehydrogenase activities were also assessed. Acute and chronic blockade of nitric oxide synthase (NOS) was employed to determine whether or not NO is critically involved in functional remodelling in CH muscles. CH improved diaphragm, but not sternohyoid, fatigue tolerance in a time-dependent fashion. This adaptation was not attributable to increased SDH or NADPH dehydrogenase activities. The areal density of muscle fibres and relative area of fibres expressing SERCA2 were unchanged. Na+,K+-ATPase pump content was significantly increased in CH diaphragm. Chronic NOS inhibition decreased diaphragm Na+,K+-ATPase pump content and prevented CH-induced increase in muscle endurance. This study provides novel insight into the mechanisms involved in CH-induced muscle plasticity. The results may be of relevance to respiratory disorders characterised by CH, such as chronic obstructive pulmonary disease.

Atrophy of the sphincters of continence in an experimental model.

BACKGROUND: Pudendal nerve injury during childbirth may result in external anal sphincter (EAS) atrophy. Recently, balloon compression of the pelvic side wall has been shown to result in EAS atrophy in an experimental model. The aim of this study was to determine whether other sphincters of continence are similarly affected. METHOD: Sixteen adult female virgin Wistar rats (eight controls) were studied 4 weeks after surgery. Anal and urethral canals were dissected, snap frozen and sectioned using a cryostat (100 microm thickness). Masses of EAS, internal anal sphincter (IAS) and external urethral sphincter (EUS) were calculated stereologically and stained with succinate dehydrogenase histochemistry to differentiate striated from smooth muscle. Sphincter length was determined and total sphincter mass calculated. Data were analysed with an unpaired Student's t-test. RESULTS: Atrophy of EAS (30.9 +/- 1.7 to 21.3 +/- 1.7 mg/ kg, P = 0.001), IAS (98.1 +/- 11.3 to 67.1 +/- 5.0 mg/kg, P = 0.01) and EUS (9.6 +/- 0.98 to 7.4 +/- 0.8 mg/kg, P = 0.05) was found 4 weeks after the injury. CONCLUSION: In an experimental model of obstetric pudendal nerve injury, significant atrophy of striated and smooth muscle sphincters of continence occurs and may contribute to altered continence following vaginal childbirth.

Experimental models of neuropathic fecal incontinence: an animal model of childbirth injury to the pudendal nerve and external anal sphincter.

PURPOSE: Childbirth is the most common cause of fecal incontinence and damage to the pudendal nerve is a major component of childbirth injury. This study was designed to develop an acute animal model of injury to the innervation of the external anal sphincter. METHODS: Forty-eight female virgin wistar rats were studied. Two models of neuropathic injury were developed. Bilateral inferior rectal nerve crush (Group A) acted as a positive control. Prolonged intrapelvic retrouterine balloon inflation (Group B) simulated the pelvic compressive forces of labor. Quantitative analysis of external anal sphincter muscle function was performed by using electromyography, external anal sphincter specific force production, and stereologic calculation of external anal sphincter mass. RESULTS: Injury in both groups caused significant atrophy of the external anal sphincter (P = 0.002, ANOVA) and electromyographic evidence of reinnervation at one week. Specific force (mN force per mg mass) was not altered. External anal sphincter muscle mass recovered after four weeks in Group B. CONCLUSIONS: Balloon dilation within the boney pelvis results in denervation of the external anal sphincter and offers an experimental model of the effects of childbirth on the continence mechanism in humans.

External anal sphincter fatigue is not improved by N-acetylcysteine in an animal model.

Oxidative stress is associated with skeletal muscle fatigue. This study tests the hypotheses that N-acetylcysteine (NAC) reduces fatigue and accelerates recovery of the rat external anal sphincter (EAS). Fifteen female Wistar rats were killed humanely. The EAS was mounted as a ring preparation and electrically stimulated with 50 Hz trains of 200 ms in duration every 4 s for three and a half minutes. Three groups were analysed: a control group (n = 5), a group pretreated with NAC (10(-4) mol L(-1); n = 5) and a group pretreated with NAC (10(-3) mol L(-1); n = 5). A novel fatigue index was formulated and was compared to a conventional method of expressing fatigue. There was no significant difference at concentrations of NAC (10(-4) mol L(-1); P > 0.05). At high concentrations of NAC (10(-3) mol L(-1)) there was a significant depression in peak twitch amplitude before fatigue (P = 0.04). N-acetylcysteine in both concentrations used, did not alter fatigue or recovery of the rat EAS. There was a significant positive correlation between the two methods of expressing fatigue but the conventional method produced a higher fatigue index (22.4% on average). N-acetylcysteine does not ameliorate fatigue or accelerate recovery of the EAS and may not be a useful medical therapy for faecal incontinence.