3d Mechanical properties of the partially obstructed guinea pig small intestine

Background and aimsPartial obstruction of the small intestine results in severe hypertrophy of smooth muscle cells, dilatation and functional denervation. Hypertrophy of the small intestine is associated with alteration of the wall structure and the mechanical properties. The aims of this study were to determine three dimensional material properties of the obstructed small intestine in guinea pigs and to obtain the 3D stress–strain distributions in the small intestinal wall.MethodsPartial obstruction of mid-jejunum was created surgically in five guinea pigs that were euthanized 2 weeks after the surgery. Ten-cm-long segments proximal to the obstruction site were used for the stretch-inflation mechanical test using a tri-axial test machine. The outer diameter, longitudinal force and the luminal pressure during the test were recorded simultaneously. An anisotropic exponential pseudo-strain energy density function was used as the constitutive equation to fit the experimental loading curve and for computation of the stress–strain distribution.ResultsThe wall thickness and the wall area increased significantly in the obstructed jejunum (P<0.001). The pressure—outer radius curves in the obstructed segments were translated to the left of the normal segments, indicating wall stiffening after the obstruction. The circumferential stress and the longitudinal stress through the wall were higher in the obstructed segments (P<0.02). This was independent of whether the zero-stress state or the no-load states were used as the reference state.ConclusionThe mechanical behaviour of the obstructed small intestine can be described using a 3D constitutive model. The obstruction-induced biomechanical properties change was characterized by higher circumferential and longitudinal stresses in the wall and altered material constants in the 3D constitutive model.     

Biomechanical remodelling of obstructed guinea pig jejunum

Data on morphological and biomechanical remodelling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cm H₂O. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner.     

FMRFamide enhances acetylcholine-induced contractions of guinea pig ileum

Isolated guinea pig ilea were contracted with acetylcholine (ACh) in the absence and presence of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2). FMRFamide (0.17-17 microM) enhanced ACh-induced contractions (observed as a leftward shift of the dose-response curve and increase in Emax) with maximal effect at 1.7 microM. FMRFamide had no effect when administered alone. These results extend the demonstration of a FMRFamide/ACh interaction to mammalian tissue and support the concept that FMRFamide, or mammalian equivalents, could play a modulatory role in mammals.     

Modeling of the H-reflex facilitation during ramp and hold contractions

Healthy subjects were asked to make a voluntary ramp and hold contraction. The duration of the ramp stage was 500 ms, and the torque increment in this period was set to 15 Nm. The contraction was made from a relaxed and from a 5 Nm background torque situation. Hoffmann (H-) reflexes were elicited during the voluntary contraction, mostly with 100 ms intervals. These experiments showed an increase (facilitation) in the H-reflex before the torque or the EMG started to increase. This facilitation of the H-reflex remained during all the stages of the voluntary movement and declined to normal levels again only at the very end of the hold phase, which lasted for one second. This specific pattern of facilitation during a voluntary contraction was modeled using a modeling language, that is specifically designed to calculate neuronal systems with a high degree of reality (Ekeberg et al., 1991). Our model consisted of a motoneuron pool with 200 neurons connected to an EMG-model of the human soleus muscle and an extra group of higher-level neurons for controlling the amount of decrease of presynaptic inhibition. The model was used to simulate the observed modulation of the H-reflex with both a presynaptic and a postsynaptic mechanism. Simulations showed that a continuous change in the descending control signals is needed to make the model based on postsynaptic mechanism fit with the experimental data, whereas no extra control from the CNS over the excitatory drive to the motoneuron pool is needed when the decrease of presynaptic inhibition mechanism is applied.     

Effects of antisecretory factor-derived peptides on contractions in guinea pig colon

Two antisecretory factor (AF)-derived peptides have been studied in relation to effects on motility of guinea pig colon. Colon segments were isolated from adult guinea pigs and incubated in Tyrode Ringer. Motility was measured as the force and frequency of contractions upon addition of the derived peptides AF 1 (8 amino acids (aa)) and AF 3 (10 amino acids). At the lowest concentration (5 pM), peptide AF 1 induced a negative effect on the force of contraction in colon segments; an effect that was abolished by the cholinergic agonist carbachol. Peptide AF 3 induced a significant increase in the force of colon contractions at all concentrations (5-180 pM), with carbachol only reducing the effect of peptide AF 3 at a concentration of 15 pM. Both peptides increased contractile frequency, although the overall response was lower for peptide AF 3 than for peptide AF 1. It is concluded that antisecretory factor-derived peptides may play a role in regulating colon motility such that under pathophysiological conditions, they may serve to hasten the evacuation of noxious agents from the large intestine.     

连续递增负荷条件下肌肉活动的力-电关系

目的：观察非疲劳状态下肱二头肌在静态连续递增负荷下sEMG信号的线性和非线性指标变化规律,探讨非疲劳状态下肌肉活动的力-电关系。方法：记录11名男性受试者肱二头肌在完成为时5s连续递增负荷等长收缩过程中的sEMG信号,观察线性分析指标AEMG、MPF、MF与非线性分析指标C（N）和DET%的变化规律。结果：AEMG由第1s的112.14μV逐渐上升到第5s的1277.18μV,与负荷水平呈明显线性相关;DET%从第1s的74.95下降到第5s的46.78,呈单调递减变化;MPF、MF和C（N）在本试验条件下未发生明显改变。结论：在连续递增收缩过程中,线性分析指标AEMG呈线性递增性变化,而MPF和MF无显著改变;非线性分析指标DET%随用力程度的连续递增而递减,而C（N）则保持相对稳定。     

EMG power spectra of elbow extensors during ramp and step isometric contractions

The goal of the present study was to compare electromyogram (EMG) power spectra obtained from step (constant force level) and ramp (progressive increase in the force level) isometric contractions. Data windows of different durations were also analysed for the step contractions, in order to evaluate the stability of EMG power spectrum statistics. Fourteen normal subjects performed (1) five ramp elbow extensions ranging from 0 to 100% of the maximum voluntary contraction (MVC) and (2) three stepwise elbow extensions maintained at five different levels of MVC. Spectral analysis of surface EMG signals obtained from triceps brachii and anconeus was performed. The mean power frequency (MPF) and the median frequency (MF) of each power spectrum were obtained from 256-ms windows taken at 10, 20, 40, 60 and 80% MVC for each type of contraction and in addition on 512-, 1024- and 2048-ms windows for the step contractions. No significant differences (P greater than 0.05) were found in the values of both spectral statistics between the different window lengths. Even though no significant differences (P greater than 0.05) were found between the ramp and the step contractions, significant interactions (P less than 0.05) between these two types of contraction and the force level were found for both the MPF and the MF data. These interactions point out the existence of different behaviours for both the MPF and the MF across force levels between the two types of contraction.     

Blockade of histamine-induced contractions of guinea pig ielum by beta-haloalkylamines.

In the longitudinal muscle strip of guinea pig ileum phenoxybenzamine (POB) produces a maximum parallel shift of 0.7 log units in the dose-response curve to histamine. In the presence of sodium thiosulfate in the wash fluid the parallel shift whith retention of maximum response increases to about 2 log units, and a similar value is obtained for Nethyl-N-(2-bromoethyl)-1-naphthylamine. The The agent N-ethyl-N- (2-chloroethyl)benzylamine produces a significantly smaller shift of dose-response curve of 1.53 log units before the maximum response becomes depressed. The receptor-specific depression of maximum response produced by higher doses of POB is reversed by sodium thiosulfate and by bovine serum albumin, while the parallel shift in dose-response curve is unaffected by both treatments. These findings may be explained by a hypothesis involving interaction of 2-haloalkylamines at two sites.     

Regulation of proacrosin conversion in isolated guinea pig sperm acrosomal apical segments

Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis, proacrosin has been identified in extracts of intact guinea spermatozoa as a major silver staining band which reacted immunologically with antibodies made against purified proacrosin from guinea pig testis. Proacrosin exhibited an approximate Mr of 50,000 and was rapidly converted to an Mr 45,000 protein following induction of the acrosome reaction with 2.0 mM CaCl2 and 1 micrograms/ml A23187. Apical segments isolated at pH 6.0 from guinea pig spermatozoa also contained a major silver staining band of Mr 50,000 which cross-reacted with antibodies to guinea pig testis proacrosin. Subcellular fractionation of spermatozoa indicated that proacrosin remained in the particulate fraction of homogenized spermatozoa and was enriched within the isolated acrosomal apical segment. When apical segments isolated at pH 6.0 were incubated at pH 7.5, proacrosin was rapidly converted to the Mr 45,000 form observed in spermatozoa undergoing the acrosome reaction. The conversion process in isolated apical segments was inhibited by leupeptin and was accelerated in the presence of calcium, magnesium, and manganese. Zinc completely inhibited the conversion of proacrosin to the Mr 45,000 protein. Neither proacrosin nor the Mr 45,000 protein were released into the supernatant fluid during the incubation of apical segments at pH 7.5. Furthermore, the proteins were resistant to solubilization by 150 mM NaCl and 1% Triton X-100 but were solubilized by treatment of apical segments with 1 M NaCl. These results provide evidence as to the identity and subcellular distribution of proacrosin in intact guinea pig sperm prior to zymogen conversion and suggest that isolated apical segments exhibit a subset of the exocytotic reactions leading to completion of the acrosome reaction.     

Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum

The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8-37 and 37% by NK3 (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by NK3 antagonists (66%) but were not altered by CGRP 8-37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by NK3 antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate NK3 receptors on myenteric vasodilator pathways.     

Interaction between forskolin and verapamil on spontaneous contractions of isolated guinea pig atria

Forskolin (0.16-1.3 mumol l-1 produced a concentration-dependent increase in both the isometric contraction and the atrial rate. The effects developed slowly, 5 to 8 minutes after the drug was added into the organ bath. Forskolin produced positive inotropic and chronotropic effects also in the presence of isoprenaline. The effects of forskolin were significantly inhibited in the presence of increased concentrations of verapamil in the organ bath. These results indicate that the action of forskolin is mediated by stimulation of the adenylate cyclase system, but in some steps of this action, calcium is also implicated.     

Regulation of epithelial transport in the jejunal mucosa of the guinea pig by neurokinins

This study characterizes the actions of the neurokinins and calcitonin-gene related peptide (CGRP) on electrolyte transport across the mucosa of the guinea pig jejunum in vitro in a modified Ussing chamber. By following changes in short circuit current (Isc) induced by substance P (SP) and neurokinins A & B (NKA & NKB) in the presence and absence of tetrodotoxin (TTX) and atropine, it was established that two distinct neurokinin receptors are involved in the regulation of electrolyte transport. NKA preferentially activates a neuronal receptor since the actions of this neurokinin were inhibited by both TTX and atropine. SP, whose actions were reduced to a lesser extent by TTX and atropine, is considered to activate preferentially a receptor on the epithelial cells. The third neurokinin, NKB, appears to act non-selectively on both the neuronal and epithelial receptors. CGRP, which per se did not affect Isc, markedly potentiated the increases in Isc induced by SP and NKB, and thus acts synergistically with the epithelial neurokinin receptor. These results suggest that two distinct neurokinin receptors (the NK-1 and the NK-2) regulate epithelial transport in the jejunal mucosa of the guinea pig, and furthermore indicate that at least one of the peptides found in enteric nerves (i.e. CGRP) modulates the actions of neurokinins on epithelial cells.     

Synaptic transmission in simple motility reflex pathways excited by distension in guinea pig distal colon

We examined specific receptor/transmitter combinations used at functionally identified synapses in ascending and descending reflex pathways of guinea pig distal colon. Excitatory (EJPs) or inhibitory junction potentials (IJPs) were recorded intracellularly from nicardipine-paralyzed circular smooth muscle in either the oral or anal recording chamber of a three-chambered organ bath, respectively. Blockade of synaptic transmission in the central chamber with a 0.25 mM Ca2+/12 mM Mg2+ solution abolished EJPs evoked by distension applied either in the central or the far (anal) chamber. IJPs evoked by distension in the central or the far (oral) chamber were depressed to approximately 50% of control. Hexamethonium (nicotinic receptor antagonist, 200 microM) in the central chamber reduced IJPs evoked by far or central distension to 50%, whereas EJPs evoked by far distension were abolished and EJPs evoked by central distension were reduced to 70% of control. Hexamethonium in the recording chambers reduced both IJPs and EJPs evoked by central distension to approximately 50%. EJPs in the ascending pathway were unaffected by blockade of muscarinic receptors in the central chamber or blockade of neurokinin 3 tachykinin receptors in this or the recording chamber. In the descending pathway, blockade of P2 receptors in the same chambers had only a minor effect on distension-evoked IJPs. Thus some intrinsic sensory neurons of guinea pig colon have long descending projections (>30 mm), but ascending projections of <15 mm. In contrast to the ileum, transmission between ascending or descending interneurons and from sensory neurons to descending interneurons is predominantly via nicotinic receptors; but transmission to inhibitory or excitatory motoneurons and from sensory neurons to ascending interneurons involves nicotinic and other unidentified receptors.     

Sources and implications of basal nitric oxide in spontaneous contractions of guinea pig taenia caeci

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), the neuronal blocker tetrodotoxin (TTX, 10(-6) M), or both on spontaneous contractions and on the production of basal NO. Both L-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by L-NAME and was inhibited by 38% by TTX. When tested together, L-NAME in the presence of TTX or TTX in the presence of L-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.     

Neuropeptide Y: prejunctional inhibition of vagally induced contractions in the guinea pig trachea

The effects of neuropeptide Y (NPY) on the contractile response to vagus nerve stimulation at different frequencies was studied in an isolated tracheal tube preparation from guinea pig. NPY had no effect on basal smooth muscle tension or on the contractile effect of carbachol, but inhibited vagally induced contractions in a concentration-dependent manner with a greater inhibition at low frequencies than at high. We suggest that the effect is exerted prejunctionally.     

Motor unit recruitment and EMG power spectra during ramp contractions of a bifunctional muscle.

Surface electromyograms (EMGs) were analysed on the short and long head of the biceps brachii (BBSH and BBLH) during single (F and S) or dual (F+S) flexion and supination tasks. It was confirmed, by the analysis of EMG root-mean-square (RMS) values, that the highest activations of BBSH and BBLH were obtained during a maximal dual task. This study was essentially concerned with the analysis of power spectra data obtained during progressive or ramp contractions (RCs). The shape of the power spectra established during the first second of the RCs differs between F, S and F+S tasks. Differences in mean power frequency (MPF) calculated during RCs would be representative of a recruitment of motor units (MUs) that is, at least partly, task-dependent. In order to compare MPF values calculated from RCs performed under different mechanical conditions (F, S and F+S), MPF-RMS(PSD) relationships have been established (RMS(PSD) being defined as the power spectrum density RMS). Both BBSH and BBLH exhibited initial MPF values higher in supination RC than in flexion RC. Because of plateau values reached at the same level of muscle activation whatever the task performed, the slope of the MPF-RMS(PSD) relationship was lower in S than in F. These results are in favour of MU recruitment that is, at least partly, different in F and in S conditions. Dual submaximal tasks seem to mix the activation of the F and S subpopulations of MUs as revealed by the spectral parameters obtained during F+S ramp contractions. This study could find some implication in the field of muscle rehabilitation or reinforcement.