Effects of 12 Weeks of Essential Amino Acids (EAA)-Based Multi-Ingredient Nutritional Supplementation on Muscle Mass, Muscle Strength, Muscle Power and Fatigue in Healthy Elderly Subjects: A Randomized Controlled Double-Blind Study.

OBJECTIVE: To counteract muscle mass, muscle strength and power loss during aging, and to study age-related change of neuromuscular manifestation of fatigue in relation to nutritional supplementation. DESIGN: randomized controlled double-blind study. SETTING: Twice-daily consumption for 12 weeks of an Essential Amino Acids (EAA)-based multi-ingredient nutritional supplement containing EAA, creatine, vitamin D and Muscle Restore Complex®. PARTICIPANTS: 38 healthy elderly subjects (8 male, 30 female; age: 68.91±4.60 years; body weight: 69.40±15.58 kg; height: 1.60±0.09 m) were randomized and allocated in supplement (SUPP) or placebo (PLA) group. Mean Measurements: Vitamin D blood level; Appendicular Lean Mass (ALM); Visceral Adipose Tissue (VAT); Maximal Voluntary Contraction (MVC) and Peak Power (PP); myoelectric descriptors of fatigue: Fractal Dimension and Conduction Velocity initial values (FD iv, CV iv), their rates of change (FD slopes, CV slopes) and the Time to perform the Task (TtT). Mean Results: Significant changes were found in SUPP compared to baseline: Vitamin D (+8.73 ng/ml; p<0.001); ALM (+0.34 kg; p<0.001); VAT (-76.25 g; p<0.001); MVC (+0.52 kg; p<0.001); PP (+4.82 W; p<0.001). Between group analysis (SUPP Vs. PLA) showed improvements: vitamin D blood levels (+11,72 ng/ml; p<0.001); Legs FFM (+443.7 g; p<0.05); ALM (+0.53 kg; p<0.05); MVC (+1.38 kg; p<0.05); PP (+9.87 W; p<0.05). No statistical changes were found for FD iv, CV iv, FD and CV slopes and TtT, either compared to baseline or between groups. Significant correlations between mean differences in SUPP group were also found. CONCLUSION: The study demonstrates that in healthy elderly subjects an EAA-based multi-ingredient nutritional supplementation of 12 weeks is not effective to change myoelectric manifestation of fatigue and TtT failure but can positively affect muscle mass, muscle strength, muscle power and VAT, counterbalancing more than one year of age-related loss of muscle mass and strength.

Acute exposure to essential amino acids (EAA) activates MTOR/p70 signaling in soleus muscle of chronically EAA-treated aged rats.

Using an in vitro assay we assessed whether the acute exposure of soleus muscle of adult and aged rats to essential amino acid enriched mixture (EAAem) activates mTOR signaling pathway (mTOR and p70S6K) even after prolonged supplementation with the same mixture. A total of 20 adult (9 months of age at the end of treatment) and 20 aged (18 months of age at the end of treatment) male Wistar rats were used. Ten of each group were treated with EAAem (1.5 gr/kg/day in tap water) for 6 months. At the end of treatment the rats were grouped (n = 5 each group) as follows: adult (AD) and aged (AG) untreated controls; adult (AD_EAAem) and aged (AG_EAAem) chronically supplemented with EAAem; adult (AD+EAAem) and aged (AG+EAAem) acutely incubated with EAAem (soleus in 1 percent EAAem for 30 min); AD_EAAem+ and AG_EAAem+ acutely incubated with EAAem. Following treatment the activation level of mTOR and p70S6K was measured by Western blot. The basal level of mTOR and p70S6K activation appeared to be higher in AD compared with AG. In AG+EAAem a significant change in the level of p70S6K activation, unlike mTOR, was observed whereas no change was observed in AD+EAAem. In AD_EAAem muscles the basal level of p70S6K activation, unlike mTOR, was significantly lower than in AD and the acute exposure to EAAem produced a significant reduction of mTOR activation. Contrarily to AG, in AG_EAAem+ the acute exposure to EAAem produced a significant activation of mTOR, unlike p70S6K. Results in the adults indicated a higher basal level of activation and a lower responsiveness of the pathway to acute and chronic exposure to EAA-enriched mixture. On the contrary, in the aged, a lower basal level of activation was associated with a higher responsiveness to EAAem. In particular, although with a different timing, acute exposure to EAAem activated mTOR signaling even following prolonged supplementation.

Variability in muscle adaptation to electrical stimulation.

The aims were to investigate the plasticity of the myosin heavy chain (MHC) phenotype following neuromuscular electrical stimulation (NMES) and to assess the correlation between MHC isoform distribution and muscle fibre conduction velocity (MFCV).14 men were subjected to 24 sessions of quadriceps NMES. Needle biopsies were taken from the dominant vastus lateralis and neuromuscular tests were performed on the dominant thigh before and after training. NMES significantly increased the quadriceps maximal force by 14.4±19.7% (P=0.02), vastus lateralis thickness by 10.7±8.6% (P=0.01), vastus lateralis MFCV by 11.1±3.5% (P<0.001), vastus medialis MFCV by 8.4±1.8% (P<0.001). The whole spectrum of possible MHC isoform adaptations to training was observed: fast-to-slow transition (4 subjects), bi-directional transformation from MHC-1 and MHC-2X isoforms toward MHC-2A isoform (7 subjects), shift toward MHC-2X (2 subjects), no MHC distribution change (1 subject). No significant correlation was observed between MHC-2 relative content and vastus lateralis MFCV (pre-training: R2=0.04, P=0.46; post-training: R2=0.02, P=0.67). NMES elicited distinct adaptations in the MHC composition and increased force, muscle thickness, and MFCV. The MHC isoform distribution did not correlate with MFCV, thus implying that the proportion of different fibre types cannot be estimated from this electrophysiological variable.

An electromyographic study of the vastii muscles during open and closed kinetic chain submaximal isometric exercises.

BACKGROUND: Rehabilitation programs for patients with patellofemoral dysfunction aim to recruit the vastus medialis obliquus muscle (VMO) in an attempt to reduce pain and to improve patellar tracking. OBJECTIVES: The aim of the present study was to use surface EMG to assess the effectiveness of two isometric submaximal contractions (10% and 60% of maximal voluntary contraction, MVC) in promoting preferential activation of VMO over vastus medialis longus (VML) and vastus lateralis (VL) in open and closed kinetic chain isometric exercises with the knee joint fixed at 30, 60 and 90 degrees of flexion. METHODS AND MEASURES: Surface electromyography (EMG) signals were recorded with linear adhesive arrays of four electrodes from fourteen healthy young men (age 23.5±3.2, mean±SD) during isometric knee extension contractions at 10% and 60% of the maximum voluntary contraction (MVC) for 1 min and 20 s respectively at 30, 60 and 90 degrees of knee flexion. Initial values and rate of change (slope) of mean frequency (MNF), average rectified value (ARV) and conduction velocity (CV) of the EMG signal were calculated. RESULTS: Comparisons between the force levels produced at 10% and 60% MVC revealed that the initial values of ARV and CV for the VL, VML and VMO muscle were greater at 60% MVC compared to 10% MVC (3-way ANOVA; F=536; p<0.001, F=49: p<0.01 for ARV and CV respectively). Comparisons between the different muscles demonstrated lower initial values of CV for VMO compared to VL and VLM at 10% and 60% of MVC (F=15; p<0.05). In addition, initial estimates of ARV were higher for VMO compared to VML at both force levels (F=66; p<0.05). Comparisons between open and closed kinetic chain exercises revealed higher initial estimates of ARV for open kinetic chain knee extension at both force levels (F=62; p<0.01). In addition, the absolute value of MNF slope appeared to increase at higher angles for closed kinetic chain at 60% MVC while it was minimum at 60° degrees for open kinetic chain. No significant differences were observed in the rate of change of CV and MNF among the three muscles. CONCLUSIONS: Based on the results of this study, both open and closed kinetic chain exercise similarly activate the three portions of the quadriceps muscle, suggesting that selective training of the vastii muscle is not achievable in these conditions.

Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats.

The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.

Subcutaneous Ewing sarcoma/PNET as a second cancer in a previously irradiated young patient. an uncommon type of post-irradiation soft tissue sarcoma.

Soft tissue sarcomas account for a small proportion of second cancers, with an estimated frequency of < 10%. The most common histologic type of soft tissue sarcomas as second cancers include mostly high-grade sarcomas, such as rhabdomyosarcoma, malignant peripheral nerve sheath tumour, fibrosarcoma, leiomyosarcoma, synovial sarcoma, alveolar soft part sarcoma and Ewing sarcoma/primitive neuroectodermal tumour (PNET). We report a case of superficial soft tissue Ewing sarcoma/PNET as a second cancer in a young patient previously treated for Hodgkin's disease (HD). To the best of our knowledge and based on a literature search, this is the first reported case of post-irradiation soft tissue Ewing sarcoma/PNET as a second cancer arising in the same area irradiated for cure of HD.

Steroid myopathy: some unresolved issues.

Steroid myopathy is a non-inflammatory toxic myopathy that occurs as side effect of exogenous and endogenous glucocorticoid excess. The purpose of this review is to examine issues that limit our understanding of this myopathy with respect to nosology, etiopathogenesis, conditioning factors, and muscle fiber selectivity. We suggest that if more data were available on these issues, the understanding of steroid myopathy would be enhanced substantially, thus allowing an early detection of its occurrence (before the appearance of clinical or laboratory signs) and a proper treatment of the patients.

MR imaging of atlantoaxial joint in early rheumatoid arthritis.

PURPOSE: This study was done to assess the involvement of the atlantoaxial joint in patients with early rheumatoid arthritis and evaluate the role of magnetic resonance (MR) imaging in depicting this early joint involvement. MATERIALS AND METHODS: Twenty patients (16 women and four men, mean age 55.0±12.9 years) with clinical and laboratory evidence of early rheumatoid arthritis (mean disease duration <12 months) were included in our study. MR imaging of the atlantoaxial joint was performed in all patients within 3 months from diagnosis. The MR features were correlated with clinical and biochemical variables. RESULTS: Five (25.0%) of the 20 patients exhibited enhancement of the periodontoid synovial spaces after gadolinium administration due to inflammatory synovitis. Compared with patients without cervical involvement, these five patients showed significantly higher values of erythrocyte sedimentation rate [median 77.0 mm/h (range 25th and 75th percentile 69.0-86.0) vs median 33.0 mm/h (range 25th and 75th percentile: 9.2-52) (p=0.007)]; significantly higher C-reactive protein values [median 53.6 mg/l (range 25th and 75th percentile 21.9-81.9) vs median 14.0 mg/l (range 25th and 75th percentile 0.8-20) (p=0.03)]; higher disease activity score [median 4.2 (range 25th and 75th percentile 3.9-5.4) vs median 3.2 (range 25th and 75th percentile 2.8-3.8) (p=0.03)]. Four (80%) of these five patients presented anti-citrulline antibodies (anti-CCP) and rheumatoid factor at laboratory testing. The latter was positive in 12 of the 20 patients (66%), and anti-CCP were positive in 15 (83%). CONCLUSIONS: MR imaging showed an atlantoaxial inflammatory synovitis in 25% of patients with early rheumatoid arthritis. Our results indicate that patients with higher disease activity are likely to be at higher risk of presenting early involvement of the atlantoaxial joint. MR imaging of the cervical spine is an excellent tool for assessing the early manifestations of rheumatoid arthritis before any destructive changes occur. Therefore, MR imaging should be included in the diagnostic workup in order to provide reliable guidance for treatment choices.

Supplementation with essential amino acids in middle age maintains the health of rat kidney.

Chronic kidney diseases are a social and economic problem, and diet has long been recognized as a fundamental modulator of kidney health in human and experimental models. Age-dependent alterations in mitochondrial function play a crucial role in the development of diseases of aging, and mitochondrial disorders have been observed in experimental models of kidney failure. Recently, the beneficial dietary effect of a specific mixture of essential amino acids (EAA) has been studied in elderly subjects, but no data were collected from the kidney. The aim of this study was to assess whether daily supplementation of the diet with EAA at the beginning of senescence could preserve renal health. We used middle-aged (18-month-old) male Wistar rats fed a standard diet and water ad libitum (M-aged group) or a diet with added EAA (1.5 g/kg per day) dissolved in drinking water for 3 months (M-aged+EAA group). Young (2-month-old) rats fed a standard diet for 3 months were used as controls. Mitochondrial morphology and markers for collagen, cyt-c-oxidase, HSP60, GRP75, eNOS, iNOS, Bax, Bcl2 and VEGF were analyzed in glomeruli and tubules. EAA supplementation limited fibrosis and increased the capillary tuft area in the glomeruli of M-aged rats. VEGF and eNOS were enhanced in glomeruli and the peritubular space with the EAA-supplemented diet. Mitochondrial cyt-c oxidase, Bcl2, and chaperones increased in the distal tubules of the EAA group to levels similar to those observed in the young group. Mitochondrial area and density after EAA intake did not differ from young groups. The results suggest that prolonged EAA intake could represent a strategy for maintaining the healthy status of the kidney in M-aged animals.

Essential amino acids improve insulin activation of AKT/MTOR signaling in soleus muscle of aged rats.

Essential amino acids (EAA) improve basal muscle protein synthesis in the elderly. Nevertheless, in settings of prolonged supplementation, putative signal pathways of EAA are currently unknown. The purpose of this study was to test the effects of prolonged supplementation of EAA enriched mixture (12-L-Amin) on Insulin/Insulin-like Growth Factor-1 (IGF1) pathway by measuring total and phosphorylated Akt (Ser473) and its upstream (IRS1 at Ser636) and downstream (mTOR at Ser2448, p70S6K at Thr389) targets in basal conditions and following acute insulin (0.1 U/L) incubation in vitro. To this aim, soleus muscles were dissected from male Wistar rats divided in three groups of 7 each: adults (AD, 10 mo of age), elderly (EL, 22 mo of age) and elderly supplemented (EL-AA, 12-L-Amin 1.5gr/Kg die in drinking water for 3 mo). EL showed reduced basal and post-insulin mTOR and p70S6K activation and reduced post-insulin IRS1 degradation relative to AD. EL-AA showed an increase of post-insulin Akt activation, no change in basal and post-insulin phospho-mTOR, lower reduction of phospho-p70S6K and increased post-insulin IRS1 degradation relative to AD. These results demonstrate that chronic 12-LAmin administration exerts anti-ageing effects on the activation/inactivation of the Insulin/IGF1/mTOR pathway which is identified as putative target of EAA in the elderly.

Skeletal muscle fibre diversity and the underlying mechanisms.

The review first briefly summarizes how myosin isoforms have been identified as the major determinant of the functional variability among skeletal muscle fibres. The latter feature is a major characteristic of muscle fibres and a major basis of skeletal muscle heterogeneity and plasticity in vivo. Then, evidence is reported, which indicates that the properties of muscle fibres can vary with no change in the myosin isoform they express. Moreover, the physiological and pathological conditions (ageing, disuse, exercise training, muscular dystrophy) in which such myosin isoform independent change in functional properties occurs and the possible underlying mechanisms are considered. Finally, the known molecular bases of the functional differences among slow and fast isoforms are briefly dealt with.

Myosin and actin content of human skeletal muscle fibers following 35 days bed rest.

Biopsy samples were taken from the vastus lateralis muscle of seven male subjects pre- and post-35 days bed rest (BR). The myosin heavy chain (MHC) isoform distribution of the samples was determined by densitometry of MHC bands separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual muscle fibers were dissected from biopsy samples pre-BR (n=143) and post-BR (n=144). They were studied as regards cross-sectional area (CSA), myosin content by quantitative electrophoresis and myosin actin (M/A) ratio by densitometry of myosin and actin bands of individual muscle fibers. All fibers were typed according to their MHC isoform content determined by SDS-PAGE. A decrease in MHC-1 relative content and an increase in MHC-2X content of whole muscle samples were found, suggesting a slow to fast shift in muscle phenotype. Consistently, fiber type distribution was shifted toward type 2X and 2AX fibers. Muscle fiber atrophy occurred at variable extent among fiber types. Myosin concentration was significantly lower in type 1 and type 2A muscle fibers post-BR than pre-BR, whereas M/A ratio did not vary. The latter findings indicate a disproportionate loss of myosin compared with fiber CSA and a proportional loss of myosin and actin.

Single muscle fiber properties in aging and disuse.

Since the middle of the 1980s, it was understood that myosin, the motor of contraction, can be expressed in several isoforms. The isoforms of the myosin heavy-chain (MHC) portion of the molecule were found to be mostly responsible for the diversity in the contractile and energetic properties of muscle fibers. In humans, three MHC isoforms are expressed in limb muscles (MHC-1, MHC-2A and MHC-2X) and they generate three pure fiber types (types 1, 2A and 2X) and two hybrid types (types 1-2A and -2AX). Type 1, 2A and 2X fibers widely differ with respect to most of their contractile and energetic properties, and a change in their relative distribution within muscles is known to modulate their functional properties in vivo through a "qualitative" mechanism. On the basis of the MHC regulation of muscle fibers properties, it is expected that a given fiber type develops the same force and shortens at the same speed regardless of the physiologic and pathologic conditions under which the muscle works. Surprisingly, several evidences have been accumulating to show that in aging and disuse, the properties of a muscle fiber type can change with no change in its myosin isoform content. This short review considers the latter phenomenon and the possible underlying mechanisms.

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

T and B lymphocyte depletion has a marked effect on the fibrosis of dystrophic skeletal muscles in the scid/mdx mouse.

Abnormal connective tissue proliferation following muscle degeneration is a major pathological feature of Duchenne muscular dystrophy (DMD), a genetic myopathy due to lack of the sarcolemmal dystrophin protein. Since this fibrotic proliferation is likely to be a major obstacle to the efficacy of future therapies, research is needed to understand and prevent the fibrotic process in order to develop an effective treatment. Murine muscular dystrophy (mdx) is genetically homologous to DMD, and histopatological alterations are comparable to those of the muscles of patients with DMD. To investigate the development of fibrosis, we bred the mdx mouse with the scid immunodepressed mouse and analysed fibrosis histologically; we used ELISA analysis to determine TGF-beta1 expression. Significant reduction of fibrosis and TGF-beta1 expression was found in the muscles of the scid/mdx mice. However, we observed similar centrally located nuclei, necrosis, muscle degeneration and muscle force compared to the mdx animals. These data demonstrate a correlation between the absence of B and T lymphocytes and loss of fibrosis accompanied by reduction of TGF-beta1, suggesting the importance of modulation of the immune system in DMD.

Respiratory muscle fibres: specialisation and plasticity.

Skeletal muscles are composed of fibres of different types, each type being identified by the isoform of myosin heavy chain which is expressed as slow 1, fast 2A, fast 2X, and fast 2B. Slow fibres are resistant to fatigue due to their highly oxidative metabolism whereas 2X and 2B fibres are easily fatiguable and fast 2A fibres exhibit intermediate fatigue resistance. Slow fibres and fast fibres are present in equal proportions in the adult human diaphragm while intercostal muscles contain a higher proportion of fast fibres. A small fibre size, abundance of capillaries, and a high aerobic oxidative enzyme activity are typical features of diaphragm fibres and give them the resistance to fatigue required by their continuous activity. Because of their fibre composition, intercostal muscles are less resistant to fatigue. The structural and functional characteristics of respiratory muscle fibres are not fixed, however, and can be modified in response to several physiological and pathological conditions such as training (adaptation to changes in respiratory load), adaptation to hypoxia, age related changes, and changes associated with respiratory diseases. The properties of respiratory muscle fibres can also be modified by pharmacological agents such as beta2 agonists and corticosteroids used for the treatment of respiratory diseases.

Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles.

Maximum shortening velocity (V(0)) was determined in single fibres dissected from hind limb skeletal muscles of rabbit and mouse and classified according to their myosin heavy chain (MHC) isoform composition. The values for rabbit and mouse V(0) were compared with the values previously obtained in man and rat under identical experimental conditions. Significant differences in V(0) were found between fibres containing corresponding myosin isoforms in different species: as a general rule for each isoform V(0) decreased with body mass. Myosin isoform distributions of soleus and tibialis anterior were analysed in mouse, rat, rabbit and man: the proportion of slow myosin generally increased with increasing body size. The diversity between V(0) of corresponding myosin isoforms and the different myosin isoform composition of corresponding muscles determine the scaling of shortening velocity of whole muscles with body size, which is essential for optimisation of locomotion. The speed of actin translocation (V(f)) in in vitro motility assay was determined with myosins extracted from single muscle fibres of all four species: significant differences were found between myosin isoforms in each species and between corresponding myosin isoforms in different species. The values of V(0) and V(f) determined for each myosin isoform were significantly correlated, strongly supporting the view that the myosin isoform expressed is the major determinant of maximum shortening velocity in muscle fibres.

Analysis of motor patterns in the isolated guinea-pig large intestine by spatio-temporal maps.

We investigated and quantified the spontaneous patterns of motility in the isolated guinea-pig proximal and distal colon taken from adult animals. During spontaneous emptying, profiles of proximal and distal colon were recorded with a video camera, and image analysis was used to construct spatio-temporal maps of the motions of the intestinal wall. Four patterns of motility were recorded. In the proximal colon there were neurally mediated contractions that propagated in the aboral direction at 4.1 mm s(-1), gently pushing the soft contents aborally; these are likely to represent spontaneous peristaltic behaviour. A second pattern, insensitive to tetrodotoxin (TTX; 0.6 microM), consisted, in both oral and aboral propagation, of shallow contractions of the circular muscle (ripples). These contractions propagated aborally at 2.8 +/- 0.45 mm s(-1) and orally at 2.03 +/- 0.31 mm s(-1) (n=10). Of these TTX-resistant contractions, 22.5% propagated both orally and aborally from a common origin. The orally propagated component of these myogenic contractions is likely to correspond to the antiperistalsis widely described in the proximal colon. In the distal colon, two patterns of motor activity were observed. One, induced by natural or artificial pellets, consisted of peristaltic contractions that pushed the pellets aborally at 0.8 mm s(-1) and expelled a pellet every 108 s. In the interval between pellet propulsion and after the distal colon had emptied all of its pellets a second, nerve-mediated pattern of motor activity, consisting of clusters of annular circular muscle contractions separated by short dilated regions, slowly propagated aborally at 0.3 mm s(-1). Both of these motor patterns were abolished by TTX (0.6 microM). A latex balloon, inserted at the oral end of the empty isolated distal colon and inflated to a size similar to faecal pellets, was propelled at 1.4 mm s(-1). Epoxy resin-covered natural pellets were propelled at a similar speed of 1.6 mm s(-1). Our data revealed that myogenic and neurogenic patterns of propagated contractions in the colon occur in isolated preparations and are involved in emptying the colon.

Propagating contractions of the circular muscle evoked by slow stretch in flat sheets of guinea-pig ileum.

Flat sheet preparations of guinea-pig ileum were stretched circumferentially and the propagation of circular muscle contractions along the preparation was investigated. Slow stretch, at 100 microm s-1, of a 50-mm long flat sheet of intestine, evoked circular muscle contraction orally, which propagated, without decrement, for up to 30 mm. This occurred despite circular muscle shortening being prevented, and in the absence of propulsion of contents. Thus, propagation in this flat sheet preparation could not explained on the basis of neuro-mechanical interactions, as previously proposed. Irrespective of the length of preparations, contraction amplitude decreased significantly in the most aboral 10-15 mm of intestine. This was not due to descending inhibitory pathways, but was associated with interruption of ascending excitatory pathways near the aboral end. Slow waves were not detected in circular muscle cells in any preparation (n=8). Smooth muscle action potentials evoked in circular muscle cells, in the presence of tetrodotoxin (TTX, 0.6 micromol L-1), did not propagate for more than 1 mm in the longitudinal axis. Propagation of circular muscle activity, evoked by slow stretch of flat sheet preparations, reveals the presence of a mechanism other than myogenic spread or the neuro-mechanical interactions previously proposed to account for propagation; the nature of this mechanism remains to be determined.