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PubMed2006

Effects of cold storage on the function and morphology of isolated urinary bladder in rat.

AIMS: We investigated the effects of 24- and 48-hr storage at 4 degrees C in Krebs solution on the function and morphology of isolated, rat urinary bladders. METHODS: Strips of bladder were obtained from eight male Sprague-Dawley rats. Six strips were harvested from each bladder and randomized to storage for 24 or 48 hr at 4 degrees C in Krebs solution or examination immediately after harvest. Contractile responses of the strips to potassium chloride (KCl), electric field stimulation (EFS), adenosine 5'-triphosphate (ATP) and carbamylcholine (CCh) were assessed. Histological examination of the bladder strips was performed. The pO(2), pCO(2), and pH of the solution in each storage container were measured at each storage time point. RESULTS: Cold storage induced a significant decrease in the amplitude of contraction in response to KCl and EFS after 24 or 48 hr of storage compared with control. The response of the bladder strips to ATP and CCh was significantly reduced after 48-hr storage compared with control, but not 24-hr storage. The pO(2) and pCO(2) decreased after cold storage. The pH increased after 24 hr of storage and remained stable between 24 and 48 hr of storage. Histological evaluation of the strips showed tissue swelling after 24 and 48 hr of storage. CONCLUSIONS: These results suggest that the morphology and function of bladder strips stored for 24 to 48 hr at 4 degrees C in Krebs solution undergo significant changes. Further studies are needed to assess the allowable time for storage of bladder tissue.

Adenosine Triphosphate↗
PubMed1981

Inotropic effects of potassium rich solutions of frog cardiac muscles.

1. Inotropic effects of potassium rich solutions on frog cardiac muscle have been studied bith in current clamp and voltage clamp conditions, using a double sucrose gap apparatus. 2. Potassium rich solutions cause either a positive or a negative inotropic effect, together with an increase or a decrease in the duration of the action potential, according to the preparation. 3. The phasic phase of contraction and the slow inward current are decreased in amplitude; the reversal potential of the slow inward current is shifted towards more negative values. 4. The tonic phase of contraction is first decreased, the increased; the effects are correlated with modifications of the background current, initially in the inward, then in an outward direction. 5. The tension level obtained in contracture experiments is increased or decreased, according to the direction of the changes in the background current. 6. The effects of potassium rich solutions are still observed in he presence of ouabain, suggesting that they are independent of any effect on the sodium-potassium pump. 7. The effects of potassium rich solutions are still observed when external sodium is replaced by sucrose; they disappear (except the effect on the background current) when external sodium is replaced by lithium. 8. The results, which indicate that potassium ions play a role in the regulation of the intracellular concentration of calcium ions, are discussed in relation to a possible K/Ca exchange mechanism, to the Na/Ca exchange and to the role of intracellular calcium stores.

Action Potentials↗
PubMed1997

Reoxygenated effluent of Tyrode-perfused heart affects papillary muscle contraction independent of cardiac perfusion.

OBJECTIVE: We determined, via a bioassay, if inotropic factors are released in the coronary circulation of the rat heart and if changes in cardiac perfusion change papillary muscle inotropy. METHODS: An isolated isometrically contracting rat papillary muscle (n = 5, acceptor) was superfused with Tyrode or with reoxygenated coronary venous effluent from an isolated isovolumically beating rat heart (donor) at 27 degrees C, which was perfused with Tyrode according to Langendorff. The superfusion solution in the muscle bath was exchanged completely in 90 s. During coronary venous effluent superfusion, the flow of the heart (donor) was changed in steps. RESULTS: The peak force of the papillary muscle (acceptor) was unaffected by a change from Tyrode to coronary venous effluent superfusion, but time to half relaxation (RT 1/2) significantly increased by 23.0 +/- 9.0% (mean +/- s.d.) and positive dF/dtmax significantly decreased by 14.6 +/- 4.7%. These twitch characteristics were unaffected by changes in coronary perfusion while in the heart isovolumic developed left ventricular pressure did increase with perfusion (the Gregg phenomenon). CONCLUSIONS: Factors that affected papillary muscle contractility are released into the coronary circulation, but their effect is independent of the magnitude of coronary perfusion.

Animals↗
PubMed1998

Mechanical and electrophysiological effects of mepivacaine on direct myocardial depression in vitro.

The effects of various concentrations (20, 50, and 100 mumol litre-1) of mepivacaine were studied in isolated guinea pig and rat right ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiological parameters. Mepivacaine produced dose-dependent depression of peak force during 0.5 to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted, especially at higher stimulation rates (2 and 3 Hz) with mepivacaine 50 and 100 mumol litre-1. In rat papillary muscle experiments, about 20% depression of peak force was shown at rested state contraction. Shortening of action potential (AP) duration (APD50: about 10%, APD90: about 10%) and rate-dependent depression of dV/dt max was observed with mepivacaine 100 mumol litre-1. In 26 mmol litre-1 K+ Tyrode's solution, mepivacaine 50 and 100 mumol litre-1 produced a dose-dependent depression of early (50 mumol litre-1: about 20%, 100 mumol litre-1: about 30%) and late (50 mumol litre-1: about 30%, 100 mumol litre-1: about 50%) force development. In slow APs, neither shortening of AP duration nor changes of dV/dt max were shown by mepivacaine 100 mumol litre-1. An approximate 30% depression of contracture induced by rapid cooling after 2 Hz stimulation rates was observed with mepivacaine 100 mumol litre-1. It may be concluded that the direct myocardial depressant effect of mepivacaine is likely to be caused by inhibition of Ca2+ release from the sarcoplasmic reticulum. The Na+ channel blocking action may contribute indirectly to the depression of contractility.

Anesthetics, Local↗
PubMed1972

The effect of dehydroemetine on isolated guinea-pig atria.

1. The mechanisms of the inhibitory effect of dehydroemetine on the heart was investigated using spontaneously contracting isolated guinea-pig atria.2. In normal Locke solution, dehydroemetine caused a reduction in the rate and amplitude of contraction of the atria. The effect was antagonized by adrenaline and augmented by acetylcholine.3. Increasing the potassium concentration of the bathing medium increased the inhibitory effect of dehydroemetine on the atria, while decreasing the potassium concentration antagonized the effect of dehydroemetine.4. The character of the inhibitory effect of dehydroemetine on the atria altered when the sodium concentration of the bathing solution was lowered to 75.6 mmol. In the normal sodium medium arrest of beat by dehydroemetine was gradual; in the low sodium medium, it was abrupt.5. In the low, as in the normal sodium medium, the inhibitory effect of dehydroemetine was more marked the higher the potassium concentration of the bathing medium.6. In both standard Locke solution and Locke solution containing 75.6 mmol sodium, the effect of dehydroemetine closely mimicked that obtained by adding excess potassium to the solution.7. On the basis of the foregoing it was suggested that dehydroemetine acts by increasing the permeability of the myocardial cell membrane to potassium thereby leading to the accumulation of potassium in the extracellular space.

Acetylcholine↗
PubMed1988

Comparison of the effects of oxygen, 5-hydroxytryptamine, bradykinin and adrenaline in isolated human umbilical artery smooth muscle.

The actions of 5-HT, bradykinin and adrenaline on the isolated human umbilical artery (HUA) were examined in paired isometric and isotonic preparations and in paired isometric and perfused preparations at both low (approximately 20 mmHg) and high (approximately 120 mmHg) oxygen tensions. The response to each agonist was potentiated by the higher oxygen tension in all test systems. The relative potency of the three agonists studied was similar using each of the experimental techniques. The contractions to stepped increments in oxygen tension were compared in isometric and isotonic preparations. The thresholds were found to be 20 and 28 mmHg respectively. The maximum contraction occurred at 234 and 199 mmHg respectively. In the perfused (constant flow rate) preparations, oxygen did not evoke any increase in perfusion pressure unless the vessel was held under longitudinal tension, in which case the pressor responses were similarly concentration dependent as for isometric and isotonic preparations. Responses to 5-HT, bradykinin and adrenaline in the perfused preparation were similar with or without application of longitudinal tension. It is concluded that oxygen may contract only the longitudinal muscle whereas 5-HT, bradykinin and adrenaline act on both longitudinal and circular muscle. The possible roles which these agonists may play in the regulation of umbilical blood flow are discussed.

Bradykinin↗
PubMed1975

Graded activation in rabbit mesotubarium smooth muscle.

The outer margin of the mesotubarium superius, an accessory ligament from the femal rabbit reproductive system, contains a long and slender bundle of smooth muscle fibers well aligned with the long axis of the tissue. Very little connective tissue is present. Massive alternating-current electrical field stimuli (variable in frequency, amplitude, and duration) applied to isolated mesotubaria from mature, nonpregnant animals produced contractions in which isometric force (P) and its first derivative (dP/dt) could be continuously graded; an optimum existed for stimulus frequency and amplitude, but not for its duration. Twitchlike contractions could not be produced. Isometric contractions in which P was plotted against dP/dt to generate a phase-plane trajectory were used to predict the ultimate (time = infinity) force (Po) in graded contractions; this value agreed with the Po derived from isotonic force-velocity curves fitted to the Hill equation. Quick stretches applied during the rise of contractile force revealed a slow onset of the ability to bear the Po force.

Animals↗
PubMed1990

Muscle length, shortening, myoplasmic [Ca2+], and activation of arterial smooth muscle.

The effect of muscle length on smooth muscle contraction was evaluated by measuring myoplasmic [Ca2+] (with aequorin), myosin light chain phosphorylation, length, and isometric stress in histamine-stimulated swine carotid media preparations. Tissues were equilibrated at the optimal length for stress development (Lo). Isometric contractions at short tissue lengths (0.7 Lo) were associated with a decrease in maximal stress development. Isometric contraction at 0.7 Lo also reduced the sensitivity to histamine as measured by steady-state increases in [Ca2+], phosphorylation, or stress. This suggests that decreased agonist sensitivity at shorter lengths is caused by reduced Ca2+ mobilization. Isotonic shortening also led to decreases in histamine sensitivity. Isometric contractions at 1.2 Lo were not associated with significant changes in histamine-induced increases in [Ca2+]. The [Ca2+] dependence of phosphorylation was not altered at 0.7 or 1.2 Lo. Sinusoidal length changes from 0.95 to 1.05 Lo at 1 Hz were not associated with significant changes in the resting or histamine-stimulated [Ca2+]. These results suggest that Ca2+ mobilization and the resulting contraction is relatively independent of length changes near Lo. Inactivation occurs at lengths substantially below Lo where Ca2+ mobilization by agonists is impaired.

Aequorin↗
PubMed1996

Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro.

In Duchenne muscular dystrophy (DMD) muscle cells which lack dystrophin, contraction seems to be a dominant factor contributing to the abnormal elevated intracellular calcium level. Human normal and DMD contracting myotubes cocultured with nervous cells were exposed to a hypotonic medium to mimic contraction-induced mechanical stress on the membrane, and the cytoplasmic calcium activity was simultaneously monitored (Indo-1). Hypotonic shocks induced a reversible [Ca2+]i increase in 81% of the DMD cells vs. 54% of control. In addition, responses were qualitatively different: most of DMD myotubes displayed a fast increase of Ca2+ flowing from the edge of the myotube while the response in normal cells was slow and diffuse. The fact that these responses were not affected by ryanodine, was in favour of an external source of Ca2+ involved in the hypoosmotic shocks. The localized increase of Ca2+ in DMD myotubes, inhibited by Gd3+, could result from sites of high mechanosensitive channel activity or density which could constitute a pathway for Ca2+ entry provided these cells contract.

Calcium↗
PubMed1996

Synchronous behavior of spontaneous oscillations of sarcomeres in skeletal myofibrils under isotonic conditions.

An isotonic control system for studying dynamic properties of single myofibrils was developed to evaluate the change of sarcomere lengths in glycerinated skeletal myofibrils under conditions of spontaneous oscillatory contraction (SPOC) in the presence of inorganic phosphate and a high ADP-to-ATP ratio. Sarcomere length oscillated spontaneously with a peak-to-peak amplitude of about 0.5 microns under isotonic conditions in which the external loads were maintained constant at values between 1.5 x 10(4) and 3.5 x 10(4) N/m2. The shortening and yielding of sarcomeres occurred in concert, in contrast to the previously reported conditions (isomeric or auxotonic) under which the myofibrillar tension is allowed to oscillate. This synchronous SPOC appears to be at a higher level of synchrony than in the organized state of SPOC previously observed under auxotonic conditions. The period of sarcomere length oscillation did not largely depend on external load. The active tension under SPOC conditions increased as the sarcomere length increased from 2.1 to 3.2 microns, although it was still smaller than the tension under normal Ca2+ contraction (which is on the order of 10(5) N/m2). The synchronous SPOC implies that there is a mechanism for transmitting information between sarcomeres such that the state of activation of sarcomeres is affected by the state of adjacent sarcomeres. We conclude that the change of myofibrillar tension is not responsible for the SPOC of each sarcomere but that it affects the level of synchrony of sarcomere oscillations.

Animals↗
PubMed1989

Nutrient solution may alter the effect of the H2 blocker famotidine in the guinea pig papillary muscle.

The effect of different nutrient fluids (Ringer or Krebs) on the antagonism induced by the new H2 blocker famotidine against histamine was studied in the guinea pig isolated papillary muscle. The response to histamine was the same in Ringer and in Krebs solutions, as for threshold concentration and maximum response, conversely the antagonism induced by famotidine was found to be dependent on the nutrient fluid employed. It was competitive for low concentrations of the drug in both fluids, whereas the unsurmountable antagonism caused by higher concentrations in Ringer was reversed into a classical competitive one in Krebs. The potency of famotidine did not vary (pA2 values = 7.86 and 8.09 in Ringer and Krebs, respectively). The addition of PO4 or Mg++ to Ringer or the pH adjustment, in order to minimize the differences in the ionic content, did not modify the results obtained. The above data suggest that the antagonism by high concentrations of famotidine against histamine may be competitive or unsurmountable according to the nutrient fluid employed and stressed the importance of the ionic environment in the drug-receptor interaction.

Animals↗
PubMed2006

Models of metabolic utilization predict limiting conditions for sustained power from conditioned skeletal muscle.

Application and development of muscle powered cardiac assist devices is limited by the ability to predict the sustainable power output of in situ conditioned muscle under the expected loading conditions and geometrical constraints. Empirical definition of the sustained power limits and representative models of the bounding conditions where continuous power can be obtained are needed for device design and optimization. The latissimus dorsi muscles of four goats were chronically conditioned for 11 weeks with an implanted myostimulator. The ability to sustain power under isotonic conditions was evaluated across a range of contraction durations (100-600 ms) and rates (10-120 contractions/min). Muscles were characterized both biomechanically and myothermically to develop and evaluate three increasingly complex empirically-based models of metabolic utilization per contraction based on (1) the duty cycle, (2) a linear function of activation time, and (3) a multivariate-derived function of contraction duration, muscle load, and shortening distance. A clearly defined boundary for sustainable stimulation conditions was observed and was best represented by the linear metabolic model. These data provide both an empirical measure of chronically sustainable muscle power and predictive metabolic models that may be used to optimize the power harnessed for skeletal muscle actuated devices.

Adaptation, Physiological↗
PubMed1990

Responses of human muscle spindle afferents during isotonic position holding and active movements.

Discharge characteristics of muscle spindle primary afferents from human finger flexors were investigated during load-bearing isotonic position holding, and intentional shortening or lengthening contractions. During position holding, units mostly showed a negative relationship between muscle length and impulse rate, particularly when the load was small. When the load was increased, Ia-discharge rates increased more in the elongated than in the shortened muscle, and the inverse position response became less pronounced. During active lengthening contractions, a stretch response pattern was sometimes absent or could be abolished by increasing the load.

Adult↗
PubMed1986

Computer-based assessment of habitual mastication.

A computer-based system to assess mandibular movements and EMG masseter and temporal muscle activity during habitual mastication was applied to 12 healthy subjects and the chewing performance was tested with a standardized bolus of crisp bread. A Siemens Sirognatograph instrument was used to record mandibular movements while EMG signals were recorded with surface silver-silver electrodes. Software provided data of single chewing cycles in space and versus time, of mean mandibular displacement during opening and closing, mean velocity, and EMG activity. Clockwise and counterclockwise cycles were computed separately. The data obtained allow the following conclusions: Habitual mastication is a rhythmic event with different envelopes of motion that alternate characteristically in each subject. Each chewing cycle accomplishes several tasks but, depending on its envelope, is probably more oriented to a specific performance. A mean chewing cycle can be constructed for each individual. Its pattern depends on the distribution of different envelopes of motion that alternate during the masticatory sequence. During closure, a prevalently isotonic and a prevalently isometric phase of muscle contraction can be distinguished. Mean movement and EMG data for the whole group are not distributed at random, but according to a typical pattern. The system seems to be finalized to a well-balanced function and distribution of loads.

Adolescent↗
PubMed2006

Effect of hypoxia-reoxygenation on endothelial function in porcine cardiac microveins.

BACKGROUND: The cardiac venous system possesses up to 30% of total coronary vascular resistance and the effect of hypoxia-reoxygenation (H-R) and St Thomas (ST) cardioplegic solution on the vein is unknown. We investigated the effects of H-R, with or without ST, on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in porcine cardiac microveins under clinically relevant temperatures. METHODS: The microveins (diameter 200 to 450 microM) mounted in a myograph were subjected to hypoxia (Po2 < 5 mm Hg) for 30 minutes in Krebs solution (n = 8) or for 60 minutes in Krebs (n = 8) or in ST at 37 degrees C (n = 8) or 4 degrees C (n = 8), followed by 30-minute reoxygenation. The microvein was precontracted with thromboxane A2 mimetic U46619 (-7 log M) and the EDHF-mediated relaxation was induced by bradykinin (-10 to -6 log M) in the presence of indomethacin, NG-nitro-L-arginine, and oxyhemoglobin before and after H-R. RESULTS: The maximal EDHF-mediated relaxation was significantly reduced after 30-minute hypoxia (38.7 +/- 2.0% vs 61.1 +/- 2.3%, n = 8, p < 0.001) or 60-minute hypoxia in either Krebs or ST at 37 degrees C (Krebs: 27.8 +/- 1.2% vs 56.6 +/- 2.5%, n = 8, p < 0.001; ST: 23.8 +/- 4.1% vs 57.1 +/- 1.5%, n = 8, p < 0.001). The relaxation was significantly less after prolonged H-R in Krebs (p < 0.001). Incubation in Krebs or ST at 4 degrees C also reduced the EDHF-mediated relaxation (Krebs: 25.3 +/- 3.3%, n = 8, p < 0.001; ST: 29.1 +/- 4.4%, n = 8, p < 0.001) and there were no significant differences between Krebs and ST regarding the relaxation at either 37 degrees C or 4 degrees C (p > 0.05). CONCLUSIONS: We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microveins with more severe injury during prolonged H-R and (2) ST does not provide protection to the EDHF-mediated relaxation impaired by H-R at either 37 degrees C or 4 degrees C.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗