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A simple, non-invasive and inexpensive method for evaluating the displacement of local tissue surfaces: from vascular changes to muscle contraction.

This paper describes a non-invasive, very inexpensive method of estimating tissue displacements of various origin that is easy and fast to set up. This technique utilizes an inductive proximity sensor (IPS), which is a non-contact length transducer measuring the distance between its probe and a metal target. Its working principle is based on the electromagnetic coupling originating between the sensor probe, a source of high-frequency magnetic field, and the metal target where parasitic currents take place. The linear working range of the IPS model used here is 0.1 to 6 mm probe-target distance, its resolution is about 2 microns. The IPS has been employed on rabbits and humans to measure the displacement of a target glued to the skin of various body areas with respect to the fixed probe of the sensor. Its high resolution, together with an extensive working range, allows the evaluation of numerous physiological events which produce displacements ranging from 2 microns -- to 9 mm, reflecting either tissue volume changes or movements. In particular, an interesting application is to monitor, through volume variations, the extent and the time course of local vascular modifications induced by manoeuvres which elicit changes in vasomotor tone; vascular filling, tissue swelling etc. Therefore, this measure may be considered a 'surface plethysmography' record. In addition, the contractions of skeletal muscles, under either isotonic or isometric conditions, can be estimated through this sensor. This system may therefore find applications for research purposes and practical demonstrations to students.

Animals↗

The effect of shortening on the time-course of active state decay.

The active state describes the force developed in a muscle when the contractile elements are neither lengthening nor shortening. Recently it was suggested that perturbations used to measure the active state also alter the time-course of the active state. The present research was undertaken to assess quantitatively the effect of two such perturbations, isotonic shortening and quick release, on the active state in frog sartorius muscle. Methods were developed which allowed the determination of active state points following periods of controlled isotonic shortening or quick release early in the contraction cycle. All experiments were carried out within the plateau region of the length-tension curve. Both isotonic shortening and quick release altered the active state decay. The active state force decreased as the extent of shortening or release was increased. For each 0.1 mm of isotonic shortening there was a 2% decrease in active state force. Quick release produced a larger decrement. From this data we conclude that the time-course of active state can be measured only in relative terms because it is altered by the motion which takes place in the contractile machine while the active state is being measured. This finding helps to resolve paradoxes in the literature relating to the time-course of the active state, calculated and experimentally determined isometric tetanic myograms, and the heat of shortening.

Animals↗

Developmental changes in the response of rat isolated duodenum to nicotine.

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.

Adenosine Triphosphate↗

Isolation and characterization of a sea urchin zygote cortex that supports in vitro contraction and reactivation of furrowing.

The isolation of the cortex of the sea urchin blastomere by detergent lysis was explored with the aim of analyzing components important in the structure and function of the cortical cytoskeleton, and their relationship to such phenomena as contraction. Buffered EGTA medium supplemented with isotonic glycerol and with magnesium, at a level close to the reported internal cellular concentration, yields stable cytoskeletal cortices that retain their spherical shape. Cortices prepared this way contain actin, myosin, fascin and spectrin, components normally associated with the cortical cytoskeleton in a similar distribution to that in intact zygotes. They retain the organized cortical filamentous structure, including the actin-fascin bundles that form cores of microvilli. ATP and NaCl caused changes in cortical shape, described as either contraction or expansion, respectively. Spectrin, but not myosin, was partially extracted by NaCl, resulting in expansion of the cortex that suggests a role for spectrin in maintenance of cortical structure. ATP (but not ADP nor ATP gamma S), which caused the partial removal of myosin and spectrin, led to the contraction of the cortex, consistent with a role for myosin in cortical tension. In cortices isolated from dividing eggs, the zygotes retained their cleavage furrows and ATP induced continuation of furrow progression. This preparation appears to be a useful in vitro model for cytokinesis.

Actins↗

Ca2+ sensitivity of contractile activation during muscarinic stimulation of tracheal muscle.

The muscarinic agonists acetylcholine (ACh) and McN-A-343 act on a homogenous population of M3 receptors in canine tracheal smooth muscle; however, ACh is more effective at releasing stored Ca2+ and at stimulating inositol phosphate production. The effects of ACh and McN-A-343 on intracellular Ca2+ concentration ([Ca2+]i), myosin light chain (MLC) phosphorylation, active stress, and isotonic shortening velocity were compared to determine whether differences in their potency at stimulating second messenger pathways affected their ability to modulate the Ca2+ sensitivity of contractile filament activation. There were no differences in [Ca2+]i or isometric stress during the steady-state phase of submaximal contractions induced by ACh and McN-A-343. ACh produced slightly higher levels of MLC phosphorylation than McN-A-343; these levels were associated with much higher rates of isotonic shortening. This could indicate either an extremely high sensitivity of the shortening velocity to differences in MLC phosphorylation or that mechanisms other than MLC phosphorylation contribute to the regulation of shortening velocity. Results show that receptor-coupled pathways can modulate the relationship between [Ca2+]i and isotonic shortening velocity independently of the relationship between [Ca2+]i and isometric stress.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Depression of papillary muscle contractility by plasma incubated with pneumococci.

Mechanisms of death in pneumococcal disease are poorly understood. We have previously shown that intravenous pneumococcal products in dogs caused a mean decrease in cardiac output of 58%. The present study used measurements of the force and rate of contraction of isolated rabbit papillary muscle to determine whether pneumococci (PNC) altered myocardial contractility. Nine papillary muscles were superfused with various solutions including Tyrode's, Tyrode's incubated with sonicated type 1 PNC, normal rabbit plasma, and rabbit plasma incubated with PNC. Compared to untreated Tyrode's solution, PNC-treated Tyrode's solution did not alter papillary muscle contractility. However, compared to untreated rabbit plasma, plasma incubated with PNC caused a mean decrease of 18% in the force of contraction and 16.7% in the maximum rate of force development in nine studies. We conclude that PNC do not directly affect papillary muscle contractility. However, the interaction of PNC and plasma does cause a decrease in rabbit papillary muscle contractility.

Animals↗

Cerebral functional anatomy of voluntary contractions of ankle muscles in man.

1. Cerebral activation elicited by right-sided voluntary ankle muscle contraction was investigated by positron emission tomography measurements of regional cerebral blood flow. Two studies with eight subjects in each were carried out. Tonic isometric plantar and dorsiflexion and co-contraction of the antagonist muscles were investigated in study 1. Tonic contraction was compared with dynamic ramp-and-hold contractions in study 2. 2. All types of contraction elicited activation of the left primary motor cortex (M1). The distance between the M1 peak activation locations for tonic isometric dorsi- and plantar flexion was 17 mm. Co-contraction elicited activation of a larger area of M1 mainly located in between but partially overlapping the M1 areas activated during isolated dorsi-/plantar flexion. 3. A voxel-by-voxel correlation analysis corrected for subject covariance showed for dorsiflexion a significant correlation between tibialis anterior EMG level and cerebral blood flow activation in the cerebellum and the M1 of the medial frontal cortex. For plantar flexion a significant correlation was found between soleus EMG and cerebral activation in the left medial S1 and M1, left thalamus and right cerebellum. 4. The activation during dynamic isotonic and isometric dorsi- and plantar flexion was significantly more extensive than during tonic contractions. In addition to M1, activation was seen in the contralateral supplementary motor area and bilaterally in the premotor and parietal cortices. Isotonic and isometric contractions did not differ except in a small area in the primary somatosensory cortex. 5. One possible explanation of the different cerebral activation during co-contraction compared to that during plantar/dorsiflexion is that slightly different populations of cortical neurones are involved. The more extensive activation during dynamic compared with tonic contractions may reflect a larger cortical drive necessary to initiate and accelerate movements.

Adult↗

Effect of indapamide on volume-dependent hypertension, renal haemodynamics, solute excretion and proximal nephron fractional reabsorption in the dog.

Indapamide, a newly developed antihypertensive agent with modest diuretic properties, reduced mean arterial pressure toward normal in dogs made hypertensive with salt and DOCA, while low-dose furosemide (0.1 mg per day) and hydrochlorothiazide (1 and 50 mg per day) did not result in similar degrees of blood pressure control. Indapamide, low-dose furosemide and hydrochlorothiazide treatment all resulted in similar decreases in body weight suggesting that the antihypertensive effect of indapamide occurs through a mechanism independent of contraction of extracellular fluid volume. Intravenous indapamide at doses of 0.3, 1.0 and 3.0 mg/kg caused progressive increases in sodium, potassium and chloride excretion when urine losses were replaced by isotonic saline to prevent extracellular fluid volume contraction. Only at 3.0 mg/kg did plasma potassium decrease significantly (2.92 +/- 0.03 to 2.69 +/- 0.05 mmol/l; p less than 0.05). Neither glomerular filtration rate (GFR) nor renal blood flow (flowmeter) decreased in a dose-related manner; however, effective renal plasma flow assessed by para-aminohippurate clearance did decrease about 15% at the highest dose (p less than 0.05). Proximal re-collection micropuncture studies demonstrated decreased proximal reabsorption. Cortical diluting segment reabsorption was decreased, but CNa + CH2O/GFR increased from 7% to 11% (p less than 0.05). These results indicate that, at doses up to 3.0 mg/kg, indapamide causes a natriuresis which is modest and similar to that seen with thiazides. No decrease in GFR or renal blood flow was observed. This drug apparently exerts a natriuretic effect through an inhibition of solute reabsorption in both the proximal nephron and the cortical diluting segment.

Animals↗

Posterior rotator cuff strengthening using theraband(r) in a functional diagonal pattern in collegiate baseball pitchers.

The deceleration phase of the pitching mechanism requires forceful eccentric contraction of the posterior rotator cuff. Because traditional isotonic strengthening may not be specific to this eccentric pattern, a more effective and functional means of strengthening the posterior rotator cuff is needed. Twelve collegiate baseball pitchers performed a moderate intensity isotonic dumbbell strengthening routine for 6 weeks. Six of the 12 subjects were randomly assigned to an experimental group and placed on a Theraband(R) Elastic Band strengthening routine in a functional-diagonal pattern to emphasize the eccentric contraction of the posterior rotator cuff, in addition to the isotonic routine. The control group (n = 6) performed only the isotonic exercises. Both groups were evaluated on a KIN-COM(R) isokinetic dynamometer in a functional diagonal pattern. Pretest and posttest average eccentric force production of the posterior rotator cuff was compared at two speeds, 60 and 180 degrees /s. Data were analyzed with an analysis of covariance at the .05 level with significance at 60 degrees /s. Values at 180 degrees /s, however, were not significant. Eccentric force production at 60 degrees /s increased more during training in the experimental group (+19.8%) than in the control group (-1.6%). There was no difference in the two groups at 180 degrees /s; both decreased (8 to 15%). Theraband was effective at 60 degrees /s in functional eccentric strengthening of the posterior rotator cuff in the pitching shoulder.

Journal Article↗

Isolated human colon strips as a pharmacological tool.

The spontaneous activity of isolated human colon strips was studied to obtain homogeneous results with a reproducible model. The strips of macroscopically normal appearance were mounted in an organ bath containing Krebs solution at 32 degrees C or Tyrode solution at 37 degrees C. Mechanical activity was recorded by an isometric transducer. Spontaneous motility did not occur in all preparations. Moreover, when observed, it could not always be evaluated. The percentage of strips with spontaneous activity was lower with Tyrode solution than with Krebs solution (65 vs. 81%). KC1 did not induce a plateau contraction. Acetylcholine induced concentration-dependent contractions, with a significantly different pD2: 4.43 +/- 0.39 and 5.59 +/- 0.16 for Krebs and Tyrode, respectively. Isoprenaline abolished spontaneous motility in Krebs solution. Only 20% of specimens presented evaluable motility. Krebs solution may be the best conditions for studying the effects of drugs on spontaneous motility, while Tyrode solution can be used to investigate the effects of contractile agents.

Acetylcholine↗

Isotonic mechanics of a pharyngeal dilator muscle and diaphragm in the rat before and after fatigue.

Pharyngeal and diaphragm muscles contract and relax in synergy, which is why it was decided to compare their mechanical performance throughout the overall load continuum. The effects of fatigue were also studied. The isotonic mechanics of rat sternohyoid (SH; n=10) and diaphragm (D; n=10) were investigated in vitro. Force and length were measured in muscles contracting from zero load up to isometry. Maximum isometric tension (Pmax), peak mechanical work (Wmax), maximum unloaded shortening velocity (vzL) and mechanical efficiency (eff(max)) were recorded. Data were obtained both at baseline and after fatigue. SH muscles had a lower Pmax (96.0+/-13.7 versus 119.5+/-22.7 mN x mm(-2); p<0.05), a lower Wmax (5.5+/-1.2 versus 8.0+/-2.1 mJ x g(-1); p<0.01), a lower eff(max) (56.0+/-6.9 versus 62.6+/-5.8%; p<0.05) and a higher vzL (4.8+/-0.4 versus 3.4+/-0.4 initial length (L0) x s(-1); p<0.001) than D muscles. Wmax occurred at a higher relative load in SH (40% Pmax) than in D (30% Pmax). Fatigue did not modify eff(max) in SH muscles, whereas it significantly improved eff(max) in D muscles. These findings suggest that under control conditions, economy of force generation was less efficient in sternohyoid than in diaphragm muscles. Fatigue in sternohyoid muscles induced unfavourable mechanical behaviour. This may partly explain pharyngeal dilator muscle failure in the presence of increased loads. Whether these findings are relevant to human sleep apnoea syndrome has yet to be determined.

Animals↗

Clearance patterns of the isolated guinea pig duodenum.

To determine what role duodenal clearance plays in the resistance that the duodenum generates to gastric emptying, duodenal output in vitro was assessed under a variety of preload and after-load conditions. In the presence of an outflow resistance, duodenal output occurred in pulses related to contractions of the duodenum. Stroke volume (incremental output during a single contraction) and cumulative output increased both with the degree of duodenal filling and with pharmacological stimulation. Cumulative output decreased as outflow resistance was increased from 0.5 to 5.0 cm water pressure; there was no further decrease on raising outflow resistance to 10.0 cm water pressure. Output volume was similar from the proximal and the distal duodenum. The stroke volume produced by individual duodenal contractions remained stable over a wide range of load conditions. The threshold volume and the luminal pressure at which output from the duodenum started were higher with retrograde perfusion of the duodenum than with antegrade perfusion. Also, the contraction rate of the duodenum decreased markedly with retrograde perfusion, and the powerful contractions occurring in this setting often involved the entire segment simultaneously. The findings suggest that the duodenum responds to load and to flow conditions so that luminal clearance is maintained; clearance is achieved by both antegrade and retrograde displacement of contents from the lumen at the contraction site.

Analysis of Variance↗

[Contractile function of ureter in its anomalies in children].

A study on the testing unit was made of a contractile function of ureteral fragments removed at reconstructive operations for vesicoureteral reflux (VUR), neuromuscular dysplasia (NMD) and pelvoureteral segment stricture (PUSS). The study parameters (wall rigidity, amplitude of the contractions, potassium depolarization contracture, responses to adrenoreactive drugs) in patients with VUR were close to normal, whereas in those with NMD or PUSS changed significantly, especially in PUSS patients. Ureteral contractility impairment was heterogenic in all the groups, varying from intact to lost and did not correlate either with age or the disease stage. The value of functional studies of the ureter in reconstructive surgery for specifying the disease pathogenesis, mechanisms of functional decline and individual prognosis of functional efficiency of the operative intervention is discussed.

Adolescent↗

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. I. Contractility.

The effects of halothane, enflurane, and isoflurane on myocardial contractility were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. Isotonic and isometric variables of contractility were measured before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles), in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane, and up to 2.0 MAC of isoflurane. Each of the three anesthetics caused a dose-dependent reversible decrease in contractility. The onset of maximal myofibrillar activation was delayed in a dose-dependent manner, and time to peak shortening of the isotonic preloaded twitch was unchanged, except for a slight decrease at greater than 1 MAC of enflurane. Isoflurane's negative inotropic effects were clearly less than those of either halothane or enflurane. Comparison of the time course of contraction and relaxation in both isometric and isotonic twitches suggests that, in addition to effects on intracellular calcium availability, these anesthetics decrease the myofibrillar responsiveness to calcium and/or the calcium sensitivity of the contractile proteins.

Anesthesiology↗

Isometric and isotonic relaxation in venous smooth muscle.

The time course of relaxation under isometric and isotonic conditions was studied in preparations of rat portal vein which maintained regular phasic contractions in solutions with increased [K-+] and [Ca-2+]. It was found that the smooth muscle during isotonic lengthening was able to carry the afterload for a period of time which was longer than expected from the control isometric response. The difference was largest for afterloads corresponding to about half the isometric peak force. The terminal decline in force was identical in afterloaded and purely isometric responses. Inhibitory influences of isotonic shortening causing increased rates of relaxation, as reported for striated muscles, were not observed. The differences in the course of relaxation between isotonic and isometric responses of portal vein could not be attributed to variations in membrane excitation. It also appears that the differences are not due to changes in release or uptake of activator calcium, or to presence of viscous elements in the tissue. It is suggested that the ability of the smooth muscle to carry load over a relatively long period during isotonic relaxation may be attributed to the characteristics of the instantaneous force-velocity relations in the force range above Po.

Action Potentials↗

[Factors for voiding dysfunction and cystocele].

OBJECTIVES: To evaluate the clinical and urodynamic features of a series of women with post void residual urine (disbalanced voiding) and various degrees of associated cystocele. METHODS: 119 female patients were studied by clinical evaluation, urodynamics, and imaging tests (VCUG). All patients underwent history and genitourological examination (evaluating cystoceles from grade o to 3), neuro-urological examination, and complete urodynamic study. Fifty patients (42%) underwent radiological studies of the upper urinary tract. Disbalanced voiding was defined as existence of post void residual greater than 20% of the voided volume. Urethral resistance was measured by URA. Structural obstruction was characterized by PURR (CHESS classification). Functional obstruction was studied by DURR and perineal EMG (associated with flowmetry). Detrusor contractile power was evaluated by W max, W 80-20, and duration of contraction. Urodynamic terminology and measurements complied with the International Continence Society (ICS) standards. Statistical significance was established at 0.05. Statistical analysis was done by Student's t for quantitative variables, and Pearson's chi-square for non parametric variables. RESULTS: 119 patients were enrolled. Mean age was 55.84 yr. (range 15-87). Regarding post void residual (114 valid uroflowmetry studies), 25 patients were classified as voiding disbalance (21.9%) and 89 as balanced (74.8%). Regarding clinical data, there were only significant differences between groups in voiding difficulty. For uroflowmetry, only the percentile of the Maximal flow (Qmax) showed significant differences (35 vs. 22 for balanced/disbalanced voiding respectively, p = 0.02). Pressure/volume studies demonstrated bladder hyperactivity in 16 cases (64%) in the group of disbalanced voiding and 31 cases (34.8%) in the normal voiding group (p = 0.008), which presented associated with increased urethral resistance (URA)(p = 0.01) . In the pressure/flow study, there were significant differences in the URA (14.7 vs. 25.3, p = 0.001). There were statistically significant differences in the degree of constrictive (0.5 vs. 1.1, p = 0.009) and compressive (0.5 vs. 1.1; p = 0.04) obstruction (Chess classification). There were not significant differences in the analysis of isometric contractility (Wmax), but there were in the isotonic contractility (W80-20) and detrusor contraction duration. These latter differences presented significant association with the degree of cystocele. DURR and perineal EMG data did not show differences between groups. Radiological abnormalities of urethral morphology were statistically different between groups, presenting in 10% of the patients with normal voiding and 50% of the disbalanced voiding group, although there was not statistical association with obstruction (p = 0.64). The existence of cystocele did not show a statistical association with these variables either. CONCLUSIONS: Disbalanced voiding appeared with organic obstruction of the lower urinary tract (constrictive most significantly), as well as detrusor abnormal contractility, but whereas the first was not significantly associated with presence and grade of cystocele, the second showed such association.

Adolescent↗

Effects of tonicity on tension and intracellular sodium and calcium activities in sheep heart.

We have measured the effects of changing tonicity of the bathing solution on intracellular sodium and calcium activities and tension of sheep cardiac Purkinje strands and ventricular muscle. For Purkinje strands in solutions of normal tonicity, resting membrane potential was -77.4 +/- 0.4 mV (mean +/- SE), sodium activity was 7.9 +/- 0.4 mM, and calcium activity was 98 +/- 9 nM. For ventricular muscle in solutions of normal tonicity, resting membrane potential was -86.4 +/- 1.2 mV, sodium activity was 6.9 +/- 0.5 mM, and calcium activity was 70 +/- 4 nM. Reduction of tonicity to 75% of normal in both tissues produced depolarization of a few millivolts, and sodium activity fell almost to the level predicted for simple osmotic dilution. In Purkinje strands, calcium activity fell much more than that predicted for simple osmotic dilution. Twitch contraction was reduced in the hypotonic solution. Increase of tonicity to 150% and 200% caused the resting membrane potential to become more negative. In both tissues, sodium activity increased somewhat less than predicted from simple water movement, and calcium activity increased proportionately much more than sodium activity. The much larger change of calcium activity in both hypo- and hypertonic solutions could be explained by water movement plus the effect of sodium-calcium exchange. In hypertonic solutions, tonic tension was increased, along with the rise in calcium activity; however, the twitch tension was reduced. This reduction of twitch tension may be due to a direct effect of hypertonicity on cross-bridge behavior, as has been reported for skeletal muscle.

Animals↗

Propofol and thiopental depression of myocardial contractility. A comparative study of mechanical and electrophysiologic effects in isolated guinea pig ventricular muscle.

The purpose of the study was to compare the actions of propofol and thiopental on myocardial contractility and cellular electrophysiologic behavior. Isometric tension of isolated guinea pig right ventricular papillary muscle was studied in normal and 26 mM potassium Tyrode's solutions at various stimulation rates (after rest up to 3 Hz). Normal and slow action potentials were also recorded by conventional microelectrodes. Propofol (30, 100, and 300 microM) applied in the commercial 10% Intralipid emulsion caused dose-dependent depression of contractions at all stimulation rates, whereas Intralipid alone had no effect. Thiopental (10, 30, and 100 microM) caused depression similar to the threefold greater concentrations of propofol. Although neither drug altered the normal action potential (AP) amplitude or dV/dt max, thiopental (30 microM) increased AP duration. In the partially depolarized (26 mM potassium) beta-adrenergically stimulated myocardium, propofol and thiopental caused dose-dependent contractile depression similar to that in normal Tyrode's solution. Whereas propofol did not alter slow AP characteristics, 30-100 microM thiopental increased slow AP duration (consistent with decreased potassium conductance), and 100 microM thiopental depressed dV/dt max (consistent with decreased calcium channel ionic influx). Comparing the clinical plasma concentration ranges required for an equivalent anesthetic effect, propofol depresses myocardial contractility less than thiopental.

Action Potentials↗