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The after-contraction: a true detrusor contraction or a late dyssynergic urethral sphincter contraction?

OBJECTIVE: To evaluate the mechanism and significance of the after-contraction, recorded in bladder pressure by urodynamics, at the end of micturition. PATIENTS AND METHODS: The urodynamic recordings showing an after-contraction of the detrusor in 65 patients of all ages and with a variety of pathologies were re-examined. Special attention was directed to the anal or urethral sphincter needle electromyographic activity and to the monitored urethral pressure, to determine any relationships with the patterns of detrusor pressure. RESULTS: An after-contraction was noted in 61 patients with detrusor instability and in 11 with urethral instability. In 59 patients it was evident that the after-contraction, i.e. a renewed increase in detrusor pressure during the declining contraction, correlated with a sphincter contraction preceding it by a fraction of a second. Similar increases in detrusor pressure were apparent in patients with detrusor-sphincter dyssynergia throughout voiding. In six patients the relationship was less clear mainly because there were artefacts in the curves. CONCLUSION: The after-contraction arises by a sudden stopping of the outflow of urine, provoked by a sphincter contraction. This may occur by involuntary dyssynergia or by an early voluntary interruption of the voiding stream. The 'milk back' of urine from the proximal urethra to the bladder and the inhibited detrusor contraction (if the perineal contraction is prolonged) may cause some postvoid residual urine. It occurs mainly in the presence of detrusor and/or urethral instability.

Adult↗

Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction.

Cultured human dermal fibroblasts suspended in a rapidly polymerizing collagen matrix produce a fibroblast-populated collagen lattice. With time, this lattice will undergo a reduction in size referred to as lattice contraction. During this process, two distinct cell populations develop. At the periphery of the lattice, highly oriented sheets of cells, morphologically identifiable as myofibroblasts, show cell-to-cell contacts and thick, actin-rich staining cytoplasmic stress fibers. It is proposed that these cells undergoing cell contraction produce a multicellular contractile unit which reorients the collagen fibrils associated with them. The cells in the central region, referred to as fibroblasts, are randomly oriented, with few cell-to-cell contacts and faintly staining actin cytoplasmic filaments. In contrast it is proposed that cells working as single units use cell locomotion forces to reorient the collagen fibrils associated with them. Using this model, we sought to determine which of these two mechanisms, cell contraction or cell locomotion, is responsible for the force that contracts collagen lattices. Our experiments showed that fibroblasts produce this contractile force, and that the mechanism for lattice contraction appears to be related to cell locomotion. This is in contrast to a myofibroblast; where the mechanism for contraction is based upon cell contractions. Fibroblasts attempting to move within the collagen matrix reorganize the surrounding collagen fibrils; when these collagen fibrils can be organized no further and cell-to-cell contacts develop, which occurs at the periphery of the lattice first, these cells can no longer participate in the dynamic aspects of lattice contraction.

Adenosine Triphosphate↗

Endothelin induces two types of contractions of rat uterus: phasic contractions by way of voltage-dependent calcium channels and developing contractions through a second type of calcium channels.

Effects of endothelin on nonvascular smooth muscle have been examined using rat uterine horns and two modes of endothelin action have been revealed. Endothelin (0.3 nM) caused rhythmic contractions of isolated uterus in the presence of extracellular calcium. The rhythmic contractions were completely inhibited by calcium channel antagonists. These characteristics of endothelin-induced contractions were very similar to those induced by oxytocin. Binding assays using 125I-endothelin showed that endothelin and the calcium channel blockers did not compete for the binding sites. However, endothelin was unique in that it caused, in addition to rhythmic contractions, a slowly developing monophasic contraction that was insensitive to calcium channel blockers. This developing contraction became dominant at higher concentrations of endothelin and was also calcium dependent.

Animals↗

Myonemal contraction of Spirostomum. III. The thermal dependence of contraction, relaxation and excitation-contraction coupling.

A microphotometric technique that displays rapid length changes of Spirostomum has been used to follow the variation with temperature of these kinetic parameters of myonemal contraction: contraction rate, relaxation rate and stimulus duration at threshold. In each case the exponential form of the relationship indicated that the gross rate constant might be equated with the limiting rate constant, k, of a driving chemical reaction, and from standard expressions of chemical kinetics the change in activation free energy appropriate to this reaction has been computed.

Animals↗

Muscle inflammatory cells after passive stretches, isometric contractions, and lengthening contractions.

We tested the hypotheses that lengthening contractions, isometric contractions, and passive stretches increase muscle inflammatory cells (neutrophils and macrophages) and that prior conditioning with lengthening contractions, isometric contractions, or passive stretches reduces neutrophils and macrophages after subsequent lengthening contractions. Extensor digitorum longus muscles in anesthetized mice were subjected in situ to lengthening contractions, isometric contractions, or passive stretches. Six hours or 3 days after a protocol of contractions or passive stretches, neutrophils and macrophages were quantified in muscle cross sections. Three days after isometric contractions or passive stretches, neutrophils were elevated (P < 0.05) 3.7- and 5.5-fold, respectively, relative to controls. Both macrophages and neutrophils were increased 51.2- and 7.9-fold, respectively, after lengthening contractions. Prior lengthening contractions, isometric contractions, or passive stretches reduced inflammatory cells after lengthening contractions performed 2 wk later. The major finding of this study was that passive stretches and isometric contractions elevated neutrophils without causing overt signs of injury. Because both passive stretches and isometric contractions elevated neutrophils and afforded some protection from contraction-induced muscle injury, neutrophils and/or the related inflammatory events may contribute to the induction of a protective mechanism.

Animals↗

Excitation-contraction coupling in rested-state contractions of guinea-pig ventricular myocardium.

Different types of rested-state contractions were examined under the influence of various inotropic agents. In magnesium-free solution, in low sodium (40 mmol/l) solution or in the presence of dihydroouabain, an "early" rested-state contraction developed without delay after stimulation. A distinctive "late" rested-state contraction was observed under the influence of noradrenaline. It is characterized by a latent period of about 100 ms between stimulation and onset of contraction. This latency was not reduced by increasing the catecholamine concentration, despite a concentration-dependent increase in the height of the "late" rested-state contraction. The late rested-state contraction under the influence of noradrenaline was suppressed by the slow inward current inhibitor nifedipine whether or not the nifedipine-dependent shortening of the action potential duration was prevented by caesium. When the slow inward current was not inhibited, the prolongation of the action potential duration by caesium resulted in an increase of the late rested-state contraction because of a prolongation of the time to peak force. High concentrations of dihydroouabain led to the appearance of an early contraction component without appreciably influencing the noradrenaline-dependent late component. From this it was deduced that the activator calcium for the late rested-state contraction was not stored intracellularly during rest prior to stimulation and, consequently, could not have been released by inflowing calcium. Instead, it is proposed that the activator calcium for the late rested-state contraction entered the sites of the sarcoplasmic reticulum and subsequently released from its release sites as long as the cell was depolarized. The "early" rested-state contractions in Mg2+-free solution, in low sodium solution or in the presence of dihydroouabain were not influenced in their contraction velocity by high concentrations of nifedipine which fully inhibited the late rested-state contractions. Nifedipine caused only a slight reduction in peak force due to a shortening of the time to peak force as a result of a shortening in action potential duration. This indicates that the activator calcium for the "early" rested-state contractions had accumulated in the sarcoplasmic reticulum during rest prior to stimulation and that it was released immediately by depolarization without a participation of the slow inward current.

Action Potentials↗

A socio-legal and economic analysis of contracting in the NHS internal market using a case study of contracting for district nursing.

The introduction of an internal market in the National Health Service (NHS) in the United Kingdom necessitated the use of contracts between purchasers and providers. Little thought was given to the nature of these contracts by policy makers, who appeared to assume that the contracts could conform to the classical, complete model. This paper uses socio-legal and economic theories of contract (which provide an alternative model of relational contracts, in contrast to classical contracts) to explore how realistic that assumption was. An analysis of the institutional context in which the contracts were made is provided, including a legal analysis of the relevant legislation. Contracting by health authorities and GP fundholders is examined, using the results of a recent case study of contracting for district nursing services carried out in a health authority in Greater London. The results show that classical contracting is an inappropriate model for NHS contracts, but that relational contracting is not an entirely appropriate model either. Contracting was found to have increased the accountability of providers in respect of some financial matters, but not in respect of the quality of district nursing services. There are negative implications for the use of contracting in publicly financed health services--hierarchies may be more efficient (as lower transaction costs can be incurred) and possibly more effective in improving quality of care.

Community Health Nursing↗

Protein phosphorylation during the contraction-relaxation-contraction cycle of arterial smooth muscle.

Porcine carotid arterial muscles were labeled with 32P and then subjected to a resting-contraction-relaxation-contraction cycle. Four different agents were used for contraction: KCl, histamine, norepinephrine, and phorbol dibutyrate. To relax the contracted muscles, they were washed with physiological salt solution. Changes in the [32P]phosphate content of four different proteins--myosin light chain, a 28-kDa cytosolic protein, desmin, and caldesmon--were followed. In a short contraction-relaxation-contraction cycle lasting minutes, induced by K+, histamine, or norepinephrine, only the light chain underwent a phosphorylation-dephosphorylation-rephosphorylation without concomitant cyclic phosphorylation of the 28-kDa protein, desmin, or caldesmon. In a contraction-relaxation-contraction cycle of long duration, 60-min contractions with K+, histamine, or norepinephrine, cyclic phosphorylation of both the light chain and desmin was observed. With 60-min phorbol dibutyrate stimulation, in the long contraction-relaxation-contraction cycle, the phosphorylations of the light chain, desmin, and caldesmon were cycling. It is concluded that under physiological conditions, light-chain phosphorylation initiates both short and sustained arterial contraction. Desmin phosphorylation is likely to be involved in force maintenance during sustained contraction.

Animals↗

Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations.

1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose-6-phosphate were higher at rest and during the entire 15-min stimulation period in supercompensated muscles than in glycogen-depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = -0.52; P less than 0.01) as well as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the pre-contraction muscle glycogen concentration. Regulating mechanisms include limitations of membrane glucose transport as well as of glucose metabolism. (b) Contractions on the preceding day have a stimulating effect on glucose uptake during contractions of the same muscles on the next day.

3-O-Methylglucose↗

Calcium channels and excitation-contraction coupling in cardiac cells. I. Two components of contraction in guinea-pig papillary muscle.

Biphasic contractions have been obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) containing 0.3 microM isoproterenol; whereas in guinea-pig atria, the same conditions led to monophasic contractions corresponding to the first component of contraction in papillary muscle. The relationships between the amplitude of the two components of the biphasic contraction and the resting membrane potential were sigmoidal curves. The first component of contraction was inactivated for membrane potentials less positive than those for the second component. In Na+-low solution (25 mM), biphasic contraction became monophasic subsequent to the loss of the second component, but tetraethylammonium unmasked the second component of contraction. The relationship between the amplitude of the first component of contraction and the logarithm of extracellular Ca2+ concentration was complex, whereas for the second component it was linear. When Ca2+ ions were replaced by Sr2+ ions, only the second component of contraction was observed. It is suggested that the first component of contraction may be triggered by a Ca2+ release from sarcoplasmic reticulum, induced by the fast inward Ca2+ current and (or) by the depolarization. The second component of contraction may be due to a direct activation of contractile proteins by Ca2+ entering the cell along with the slow inward Ca2+ current and diffusing through the sarcoplasm. These results do not exclude the existence of a third "tonic" component, which could possibly be mixed with the second component of contraction.

Action Potentials↗

Lengthening contractions are not required to induce protection from contraction-induced muscle injury.

We tested the hypothesis that lengthening contractions and subsequent muscle fiber degeneration and/or regeneration are required to induce exercise-associated protection from lengthening contraction-induced muscle injury. Extensor digitorum longus muscles in anesthetized mice were exposed in situ to repeated lengthening contractions, isometric contractions, or passive stretches. Three days after lengthening contractions, maximum isometric force production was decreased by 55%, and muscle cross sections contained a significant percentage (18%) of injured fibers. Neither isometric contractions nor passive stretches induced a deficit in maximum isometric force or a significant number of injured fibers at 3 days. Two weeks after an initial bout of lengthening contractions, a second identical bout produced a force deficit (19%) and a percentage of injured fibers (5%) that was smaller than those for the initial bout. Isometric contractions and passive stretches also provided protection from lengthening contraction-induced injury 2 wk later (force deficits = 35 and 36%, percentage of injured fibers = 12 and 10%, respectively), although the protection was less than that provided by lengthening contractions. These data indicate that lengthening contractions and fiber degeneration and/or regeneration are not required to induce protection from lengthening contraction-induced injury.

Animals↗

Comparison of the efficiency of rat papillary muscles during afterloaded isotonic contractions and contractions with sinusoidal length changes.

The results of previous studies suggest that the maximum mechanical efficiency of rat papillary muscles is lower during a contraction protocol involving sinusoidal length changes than during one involving afterloaded isotonic contractions. The aim of this study was to compare directly the efficiency of isolated rat papillary muscle preparations in isotonic and sinusoidal contraction protocols. Experiments were performed in vitro (27 degrees C) using left ventricular papillary muscles from adult rats. Each preparation performed three contraction protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at 0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40 twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40 twitches at 2 Hz). The first two protocols resembled those used in previous studies and the third combined the characteristics of the first two. The parameters for each protocol were adjusted to those that gave maximum efficiency. For the afterloaded isotonic protocols, the afterload was set to 0.3 of the maximum developed force. The sinusoidal length change protocol incorporated a cycle amplitude of +/-5% resting length and a stimulus phase of -10 degrees. Measurements of force output, muscle length change and muscle temperature change were used to calculate the work and heat produced during and after each protocol. Net mechanical efficiency was defined as the proportion of the energy (enthalpy) liberated by the muscle that appeared as work. The efficiency in the low-frequency, isotonic contraction protocol was 21.1+/-1.4% (mean +/- s.e.m., N=6) and that in the sinusoidal protocol was 13.2+/-0.7%, consistent with previous results. This difference was not due to the higher frequency or greater number of twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/-1.0%. Although these results apparently confirm that efficiency is protocol-dependent, additional experiments designed to measure work output unambiguously indicated that the method used to calculate work output in isotonic contractions overestimated actual work output. When net work output, which excludes work done by parallel elastic elements, rather than total work output was used to determine efficiency in afterloaded isotonic contractions, efficiency was similar to that for sinusoidal contractions. The maximum net mechanical efficiency of rat papillary muscles performing afterloaded isotonic or sinusoidal length change contractions was between 10 and 15%.

Animals↗

Differences in wound contraction between horses and ponies: the in vitro contraction capacity of fibroblasts.

The contribution of wound contraction to wound closure determines the speed of second intention wound healing and it has been shown that significant differences exist with regard to both contraction and inflammatory response between horses and ponies and between various areas of the body. In this study, the contraction capacity of fibroblasts from limbs and buttocks of 4 Dutch Warmblood horses and 4 Shetland ponies was studied in vitro, in order to determine whether differences in wound contraction are due to differences in the inherent contraction capacity of the fibroblasts or to differences in tissue environmental factors, such as the inflammatory response. Fibroblasts were harvested from subcutaneous tissue, cultured and then suspended in both floating and anchored collagen gels. Contraction capacity was assessed by measuring the decrease in area of the floating gels and by measuring the microforces generated in the anchored gels using a custom-built measuring device. In the floating gels, no difference existed in the contraction capacity of fibroblasts from horses and ponies, or from limbs and buttocks. In the anchored gels, no differences existed between horse and pony fibroblasts, but the fibroblasts from the limbs started to contract significantly sooner and produced significantly higher forces than those from the buttocks. It is concluded that the in vivo differences in wound contraction between horses and ponies and between different sites of the body are not caused by differences in the inherent contraction capacity of fibroblasts. The in vitro differences between fibroblasts from limbs and buttocks are thought to be due to the lower proliferation rate and the longer culture time of the fibroblasts originating from the limbs, because mature fibroblasts can develop higher contraction forces than immature fibroblasts. This means that tissue environmental factors, such as cytokine profiles during the inflammatory response, determine the extent of contraction during wound healing. Further research should be directed towards the role of the inflammatory response in wound healing.

Animals↗

To contract or not to contract? Issues for low and middle income countries.

Many low and middle income countries have inherited publicly funded and provided health services, often operating at relatively low levels of technical efficiency. Changing ideas about the management of the public sector, in particular stemming from new public management theory, are spreading to these countries, whether directly or via the recommendations of multilateral and bilateral aid agencies. Pronouncements of agencies such as the World Bank imply that competitive contracting with the private sector is likely to improve the efficiency of services provision. However, very little evidence is available on whether this is likely to be the case, and in what circumstances delivery of services through contracts with the private sector is likely to be preferable to direct provision by the public sector. This paper draws on evidence from five country case-studies of contractual arrangements, in Bombay, Papua New Guinea, South Africa, Thailand and Zimbabwe, done through collaborative research between the LSHTM Health Economics and Financing Programme and local researchers in each country. A common evaluative framework was applied in each country to selected, existing contractual arrangements. Services provided under contract and evaluated included catering, cleaning, security, diagnostic services and whole hospitals. Information is presented on the design of contracts, the process of agreeing contracts including the extent of competition, and the monitoring of contract performance. A variety of evidence, including information on the relative cost and quality of contracted out versus directly provided services in the case of South Africa, Thailand, and Bombay, is used to explore whether or not contracting out to the private sector represented a preferable means of service provision. This analysis, together with information on the capacity of the agency letting the contract, and on the wider environment including the level of development of the private sector, is used to identify which aspects of the contracting process and the context in which it takes place are important in influencing whether or not contracting with the private sector is a desirable means of service provision.

Contract Services↗

Membrane charge movement in contracting and non-contracting skeletal muscle fibres.

1. The single gap voltage clamp technique (Kovács & Schneider, 1978) was used to monitor membrane charge movement in tendon-terminated short segments of cut frog skeletal muscle fibres.2. Experiments were performed both on fibres able to contract and on fibres in which contraction was eliminated by exposing the open end to a solution containing 20 mm-EGTA. In both cases ionic conductances were minimized by using a predominantly caesium glutamate solution at the open end and a predominantly tetraethyl-ammonium sulphate solution with tetrodotoxin at the closed end.3. Modifications of previously used charge movement analysis procedures included synthesis of a ;mean linear' ON and OFF capacitative transient from the OFFs of several different hyperpolarizing pulses and use of only the first 35 msec of the ;mean linear' transient so that base lines could be fitted to unaltered latter parts of ON and OFF currents for depolarizing pulses.4. Simultaneous two-micro-electrode and gap current recording from gap-clamped fibres with blocked contraction established the validity of gap-recorded charge movement currents.5. For pulses to below about 0 mV in non-contracting fibres the charges Q(ON) and Q(OFF) moved by the non-linear transient currents at pulse ON and OFF were approximately equal. For pulses to between about 0 and +50 mV Q(OFF) exceeded Q(ON), with the charge inequality increasing with both pulse amplitude and pulse duration.6. Use of 20 mm-cobalt in the solution at the closed end eliminated the ON:OFF charge inequality for large depolarizations by decreasing Q(OFF).7. The charge inequality and cobalt effect indicate that, in the absence of cobalt, ionic conductance was being slowly activated during depolarizations to between 0 and +50 mV and that inward calcium current tails were contributing to the measured Q(OFF) values. The small and slowly developing ionic current during large depolarizations was probably removed with the straight sloping base line so that Q(ON) was minimally affected by conductance activation.8. Average Q vs. V results for pulses to at most 0 mV in eighteen non-contracting fibres were well fitted by the two-state Boltzmann model where Q = Q(max)/[1+exp-(V - V)/k] with Q(max) = 26.7+/-0.6 nC/muF, k = 16.7+/-0.6 mV and V = -32.9+/-1.0 mV (least-squares values+/-s.d. obtained from fit).9. In contracting fibres the only apparent artifact produced by contraction in the I(Q) records for pulses to at most 0 mV was a ;bowing' of the OFF base lines for the larger pulses. The ON records appeared to be unaffected by contraction artifacts.10. The average Q vs. V relationship for pulses to at most 0 mV in contracting fibres was virtually identical to the one obtained from fibres in which contraction was blocked.11. The ON portions of I(Q) records for pulses to between about -50 and -25 mV exhibited prolonged tails, plateaux or secondary rising phases whereas the OFF portions decayed smoothly. I(Q) time courses were not noticeably different with or without blockage of contraction by internal EGTA.

Animals↗