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Instantaneous view of actomyosin structure in shortening muscle.

In the previous study), utilizing the rapid-freeze technique for electron microscopy, a new type of actomyosin assembly was reported to occur during isometric contraction. In this study, we have developed a new freezing apparatus which permits rapid freezing of the "isotonically-shortening" muscle at high shortening velocity, allowing simultaneous measurement of its tension and length. Using glycerinated rabbit skeletal muscle rapidly frozen with this system, we have compared the freeze-substituted images of the actomyosin assembly in the shortening muscle at various tension levels with those in isometrically-contracting muscle. The optical diffraction patterns obtained from whole A bands and from single actin filaments decorated with crossbridges have revealed that the unique actomyosin assembly formed in isometrically-contracting muscle is maintained even during high-velocity shortening under near-zero load.

Actomyosin↗

Muscle pain induces task-dependent changes in cervical agonist/antagonist activity.

This study examined the effect of experimental neck muscle pain on the EMG-force relationship of cervical agonist and antagonist muscles. Surface EMG signals were detected from the sternomastoid, splenius capitis, and upper trapezius muscles bilaterally from 14 healthy subjects during cervical flexion and extension contractions of linearly increasing force from 0 to 60% of the maximum voluntary contraction (MVC). Measurements were performed before and after injection of 0.5 ml hypertonic and isotonic saline into either the sternomastoid or splenius capitis in two experimental sessions. EMG average rectified value (ARV) of the sternomastoid, splenius capitis, and upper trapezius muscles and the muscle fiber conduction velocity (CV) of the sternomastoid muscle were estimated at 5% MVC force increments. During cervical flexion with injection of hypertonic saline in sternomastoid, ARV of sternomastoid was lower on the side of pain in the force range 25-60% MVC (P < 0.05) and was associated with a bilateral reduction of splenius capitis and upper trapezius ARV (P < 0.01). During cervical extension, injection of hypertonic saline in splenius capitis resulted in lower estimates of splenius capitis ARV on the painful side from 45 to 60% MVC (P < 0.05), which was associated with a bilateral increase in upper trapezius ARV estimates from 50 to 60% MVC (P < 0.001). However, no significant change was identified for estimates of sternomastoid ARV. Experimentally induced neck muscle pain resulted in task-dependent changes in cervical agonist/antagonist activity without modifications in muscle fiber CV.

Adult↗

Short-term ischaemic storage of human uterine myometrium--basic studies towards uterine transplantation.

BACKGROUND: Transplantation of the uterus has been suggested as a possible future treatment of absolute uterine infertility. The tolerability of human uterine tissue to cold ischaemic storage was tested in the present study. METHODS: Small tissue samples of human uteri were subjected to cold (4 degrees C) ischaemia (6 and 24 h) in Ringer acetate (RIN), the intracellular-like University of Wisconsin solution (UW) or the extracellular-like Perfadex solution (PER). The ability of myometrial strips to contract, histology by light and electron microscopy as well as tissue concentrations of glutathione, ATP and protein were used as parameters to detect cold ischaemic injuries. RESULTS: Contractile ability and response to prostaglandin F(2alpha) (PGF(2alpha)) was better preserved after 6 h cold ischaemia in UW and PER in comparison with the other groups. Histological examination did not reveal any major changes after 6 and 24 h cold ischaemic storage in UW and PER solutions, while specimens stored in RIN for 24 h displayed degenerative changes on the electron microscopy level. UW and PER preserved ATP concentrations significantly better than RIN. Myometrium stored in UW contained more total glutathione but also a larger proportion of oxidized glutathione than specimens stored in RIN and PER. Protein concentrations did not change with storage time in any of the solutions. CONCLUSIONS: The results show that human uterine myometrial tissue is resistant towards cold ischaemia for at least 6 h if stored in UW and PER solutions.

Adenosine↗

Effects of calcium and manganese ions on mechanical properties of intact and skinned muscles from the guinea-pig stomach.

1. To investigate the mechanism of generation of contractions in tissues from the guinea-pig stomach, the effects of caffeine, procaine, acetylcholine (ACh), diltiazem or MnCl(2) on the contraction evoked from small bundles of intact or skinned muscles (50 mum in width and 250-300 mum in length) were observed.2. All these agents except for ACh blocked the spontaneously generated contraction. Diltiazem (1 x 10(-4)m) had no effect and MnCl(2) (3 mm) slightly reduced and caffeine enhanced the tonic contraction evoked in Na-free solution, whereas procaine relaxed the tissue. On the other hand, in the isotonic [K](o) solution, diltiazem, MnCl(2) and procaine relaxed the tissue, while caffeine enhanced the tonic contraction.3. Under pre-treatment with Ca-free solution (2 mm-EGTA-containing solution) after depletion of the stored Ca, application of 2.5 mm-Ca and subsequently applied 5 mm-caffeine produced contractions (Ca- and caffeine-induced contractions, respectively). In polarized (5.9 mm-K(o)) and depolarized (128 mm-K(o)) muscles, the various agents simultaneously applied with 2.5 mm-Ca modified the amplitude of the Ca-induced and the resulting caffeine-induced contractions. Thus, at least three different Ca influxes required to evoke the Ca- or caffeine-induced contraction were identified; diltiazem-sensitive Ca influx, diltiazem-insensitive but Mn-sensitive Ca influx and Mn-insensitive Ca influx.4. The Ca- and caffeine-induced contractions in Ca-free and 15.5 mm-Na-containing solutions were gradually reduced in amplitude, in proportion to the time of exposure. However, amplitude of the caffeine-induced contractions was inhibited to a greater extent and the duration of the contracts was less prolonged than the case of the Ca-induced contraction.5. In saponin-treated skinned muscles, the minimum concentration of Ca required to produce the contraction was 1 x 10(-7)m, and the maximum contraction was evoked by application of 1 x 10(-5)m-Ca. The effects of Na-free solution on the Ca accumulation and release to and from the storage site were also observed in these skinned muscles. The removal of Na from the cell seems to accelerate the Ca leakage, and depletes the stored Ca. In addition, Na-free solution inhibits to some extent the accumulation of Ca in the store site.6. In skinned muscles, Mn (over 2 x 10(-9)m) significantly enhanced the Ca-induced contraction and the pCa-tension relationship shifted to the left and upper directions. Mn seemed to possess the property of activating the contractile proteins, as determined from the pMn-tension relationship, and this agent may also inhibit leakage of Ca from the store sites. However, in relation to the latter two actions, the possible effects of Ca contaminations in the solution would have to be ruled out. Under physiological conditions, MnCl(2) may act at the level of the myoplasmic membrane and not actually penetrate the cell in this tissue.

Acetylcholine↗

Effects of magnesium and temperature during the recovery process from the potassium contracture of the pregnant rat myometrium.

Effects of external ions (Na, K, Mg) on the recovery from K-contracture of the pregnant rat myometrium were investigated in Ca-free media. Relaxation was faster, when the external concentration of Na and K ions was higher. The time course of relaxation within a limited range of 60-20% of the mechanical output followed a single exponential function. The rate of relaxation, given by the reciprocal of the period during which the contraction decayed to 1/e, was 0.3-0.5 min-1 at 34-35 degrees C in isotonic Na solution. Low temperature caused prolongation of the relaxation, and the activation energy estimated on the rate of relaxation was 3-4 kcal-mol-1. Relaxation became faster when Mg (0.5-20 mM) was added to the relaxation media. Relaxation in isotonic K media was slower than in isotonic Na media, and the addition of Mg caused a slight acceleration of the relaxation. Low temperature caused an acceleration of the relaxation, irrespective of the presence or absence of external Mg ions. In low K media, where K ions were replaced by isomolar sucrose, addition of Mg caused a significant acceleration of the relaxation. Activation energy ranged between 13-15 kcal mol-1 in the solutions containing Mg. This favors the existence of a relaxing system in pregnant rat myometrium that is Mg- and metabolism-linked.

Animals↗

The risk of myocardial stunning is decreased concentration-dependently by KATP channel activation with nicorandil before high K+ cardioplegia.

BACKGROUND: Drug-induced opening of the adenosine triphosphate-sensitive potassium channel (KATP) during hypoxia and/or ischemia, achieved significant myocardial protection in several in vitro and in vivo models. Pretreatment with KATP openers simulated preconditioning and thus enhanced recovery from ischemia. We have demonstrated that the risk of hypoxia-induced myocardial stunning is reversed by KATP activation with 1 mmol/l nicorandil before cold cardioplegic arrest. Whether lower concentrations were effective is not known. METHODS: In guinea pig papillary muscle preparations contracting isometrically (driven at 1600 ms cycle), nicorandil was superfused (15 min) either 1 mumol/l (n = 4), 30 mumol/l (n = 4), 100 mumol/l (n = 4), or 1 mmol/l (n = 8) in Tyrode's solution (oxygen content 16 ml/l, 37 degrees C, 5 ml/min). Controls were superfused with saline (Tyrode's solution: n = 8). A group containing vehicle (DMSO 1%, n = 8) was also studied. In four preparations the KATP channel blocker glibenclamide 1 mumol/l was given before nicorandil 1 mmol/l. Then, long-lasting (120 min) but moderately hypoxic (oxygen content 5 ml/l: 31% of Tyrode's solution) superfusion with hypothermic (20 degrees C) high K+ (16 mmol/l) cardioplegic solution (5 ml/min) was performed. Recovery of contractility was evaluated after further 60 min of reoxygenation with Tyrode's solution based on DT/TPT (developed tension divided by time to peak tension) as percent of prehypoxia basal values (%DT/TPT60). DT/TPT was also studied following 15 min of inotropic stimulation with dobutamine 10 mumol/l (%DT/TPT75). To assess the risk of stunning, we used a multivariate linear model by all possible subsets analysis (BMDP-9R) aimed at predicting both %DT/TPT60 and %DT/TPT75 (as continuous dependent variables). RESULTS: During cardioplegia induction, time to arrest (TTA) was (mean +/- S.D.) 103 +/- 48s in control preparations which had poor recovery of contractility (stunning) after reoxygenation (%DT/TPT60: 71 +/- 20%; %DT/TPT75: 443 +/- 272%). Nicorandil (1 mumol/l-1 mmol/l) abbreviated TTA concentration-dependently (163 +/- 74, 149 +/- 103, 82 +/- 20, and 56 +/- 27s) and improved both %DT/TPT60 (63 +/- 9, 78 +/- 17, 87 +/- 13, and 98 +/- 11%) and %DT/TPT75 (587 +/- 333, 619 +/- 107, 971 +/- 301, and 666 +/- 400%). Glibenclamide reversed the effects of nicorandil 1 mmol/l (TTA: 165 +/- 30 s, P < 0.01; %DT/TPT60: 43 +/- 12, P < 0.01; %DT/TPT75: 272 +/- 147, P < 0.05). Multivariate prediction of myocardial stunning at both 60 and 75 min reoxygenation showed that nicorandil (30 mumol/l-1 mmol/l) was a significant (P < 0.001) protectant whereas glibenclamide was a significant risk factor (P = 0.009). It is unclear whether negative inotropic effects of nicorandil (%DT/TPT at the end of pretreatment) was mechanistically related to reduced risk of stunning since contribution was seen only to predict %DT/TPT75 (t = 3.24, P = 0.003) whereas a positive association was observed with %DT/TPT60 (t = 1.89, P = 0.068). CONCLUSION: Pretreatment with nicorandil concentration-dependently enhanced the cardioprotective effect of hypothermic high K+ cardioplegia. The risk of myocardial stunning was decreased by KATP opening with nicorandil and increased by KATP block with glibenclamide. Inotropic stimulation with dobutamine might unravel the role of negative inotropic effect of KATP opening as a contributory factor to explain the efficacy of nicorandil in our model.

Adenosine Triphosphate↗

[Mechanical determinants of isotonic relaxation of the isolated diaphragmatic muscle].

The aim of this study was to define the mechanical determinants of isotonic relaxation of isolated diaphragm muscle in the rat over a load range (n = 30). We tested several hypotheses to determine the effect of i) load conditions (preload, post-load), ii) sudden changes in load during contraction, iii) length of the muscle at peak shortening, iv) maximal amplitude of shortening (delta L) and v) stimulation conditions on peak rate of isotonic reelongation (+dL/dmax). At tetanus at 30 Hz, +dL/dmax was linearly correlated to delta L peak shortening and total load. Variations in preload, peak shortening or postload did not modify the +dL/dmax vs delta L relationship but such variations did affected the relationships +dL/dmax vs total load or +dL/dmax vs peak shortening. For a given value of L, +dL/dmax was weaker for twitch than for tetanus. In conclusion, four findings show that over a wide lad range the maximal amplitude of shortening the main mechanical determinant of the rate of isotonic reelongation of the isolated diaphragm muscle, independently of the length of the muscle at peak shortening, the initial length of the muscle and independently of the load during reelongation.

Animals↗

Modulatory role of magnesium on the contractile response of rat aorta to several agonists in normal and calcium-free medium.

Acute withdrawal of external Mg2+ increased basal tone of rat isolated aorta incubated in the presence of Ca2+. Above normal levels of Mg2+ (1-4 mM) inhibited basal tone while much higher levels of the divalent cation (64-256 nM) evoked contractile responses regardless of the presence of Ca2+. Contractile responses to noradrenaline (1 microM) and KCl (80 mM) were inhibited by addition of cumulative concentrations of Mg2+. Acetylcholine-induced contractions in the presence of physiological concentrations of Mg2+ (1 mM) decreased gradually to the basal tone, but a sustained contraction was observed in the absence of this ion. In Ca(2+)-free medium, acetylcholine-induced phasic responses indicate the existence of an acetylcholine-sensitive Ca2+ store. KCl induced contraction only in Krebs solution, although a small residual contraction could be observed in Ca(2+)-free medium in some experiments. Mg(2+)-depletion in the extracellular medium increased contractile responses induced by acetylcholine and KCl in Ca(2+)-free medium. These results suggest that extracellular Mg2+ modulates basal tone, Ca2+ channels and responsiveness to various agents in the absence of Ca2+.

Acetylcholine↗

Prospective, randomized trial comparing blood and oxygenated crystalloid cardioplegia in reoperative coronary artery bypass grafting.

OBJECTIVES: Reoperative coronary artery bypass grafting presents unique challenges for myocardial preservation. The purpose of this study was to compare oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during reoperative coronary artery bypass grafting using transesophageal echocardiography to assess regional wall motion of the left ventricle before and after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative coronary artery bypass grafting were prospectively randomized to receive oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered with a combined antegrade-retrograde technique. Transgastric short axis views of the left ventricle were made with transesophageal echocardiography during the operation before cardiopulmonary bypass and immediately after cardiopulmonary bypass. Regional wall motion was graded by a blinded observer, and before cardiopulmonary bypass scores were compared with after cardiopulmonary bypass scores. RESULTS: No significant differences were found in the change in regional wall motion score from before cardiopulmonary bypass to after cardiopulmonary bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This study found blood and crystalloid cardioplegia to be equally efficacious for myocardial preservation during reoperative coronary artery bypass grafting.

Bicarbonates↗

Indirect action of 5-hydroxytryptamine on the isolated muscularis mucosae of the guinea-pig oesophagus.

1 The site of action of 5-hydroxytryptamine (5-HT) was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea-pig oesophagus. Isotonic responses of the longitudinal muscularis mucosae were recorded.2 5-HT produced a transient contraction of the muscularis mucosae at concentrations higher than 3 muM. The contraction was rapid in onset, reaching a peak in about 15 s or less, and was restored to the basal level after 20 to 30 s without washing out 5-HT. When the 5-HT-induced contraction faded to the basal tone, successive applications of 5-HT no longer produced any contracture.3 Nicotine (Nic), at concentrations higher than 10 muM, also produced a transient contraction which had a very similar pattern to that induced by 5-HT. Again, the successive application of Nic no longer produced any contracture following prior treatment with Nic itself. However, the 5-HT-induced contraction was not modified by the presence of Nic.4 Exogenously applied acetylcholine (ACh) produced a concentration-dependent contraction of the muscularis mucoase, the 50% effective concentration (EC(50)) was 69 +/- 5.6 nM. The contraction was sustained during incubation with ACh, and was not modified by prior treatment with 5-HT or Nic.5 The 5-HT (100 muM)-induced contraction was completely abolished by tetrodotoxin (0.2 muM) and atropine (0.2 muM). This means that the action is mediated by stimulating cholinergic nerves in the submucous plexus attached to muscularis mucosae. Moreover, the stimulating action of 5-HT does not involve nicotinic receptors, since the action was not blocked by hexamethonium (100 muM).6 Among several 5-MT antagonists examined, methysergide (1 muM), ketanserin (1 muM) and morphine (100 muM) failed to modify the 5-HT (100 muM)-induced contraction significantly. Cinanserin (0.1-3 muM), cyproheptadine (3-100 nM) and phenoxybenzamine (0.1-3 muM) inhibited the 5-HT-induced contraction, in a concentration-dependent manner, and each highest concentration abolished the response. However, none of these antagonists was specific for 5-HT, but the Nic (100 muM) or ACh (0.1 muM)-induced contractions were also inhibited by them.7 The present results indicate that 5-HT contracts the muscularis mucosae of the guinea-pig oesophagus indirectly by stimulating cholinergic nerves in the submucous plexus, and has no direct action on the muscularis mucosae. In addition, the type of 5-HT receptors responsible for the stimulant action may be different from those in other parts of the gastrointestinal tract, blood vessels or brain, because of the different effects of 5-HT antagonists.

Acetylcholine↗

Comparison of cholinergic activation and desensitization at snake twitch and slow muscle fibre end-plates.

Characteristics of receptor-channel activation and desensitization have been compared at voltage-clamped snake slow and twitch fibre end-plates maintained in an isotonic potassium propionate solution. Miniature end-plate current (m.e.p.c.) decay was slower and less voltage dependent at slow fibre end-plates than at twitch fibre end-plates. The peak m.e.p.c. amplitude versus voltage relationship and reversal potential were similar at the two end-plate types. Acetylcholine-induced noise and m.e.p.c.s were recorded at slow fibre end-plates. At most slow fibres the spectral density was not adequately fitted by a single Lorentzian function. Rather, the observed spectral density was greater at high frequencies than the values predicted using the m.e.p.c. decay rate. The noise could be well described by the sum of two Lorentzian functions, one of which corresponded to a single Lorentzian function with the corner frequency determined by the m.e.p.c. decay rate. The shape of the carbachol concentration-peak end-plate current relationship was similar at both slow and twitch fibre end-plates. However, for all concentrations tested, the peak carbachol-induced end-plate current (e.p.c.carb.) value was markedly less at slow fibre end-plates than at twitch fibre end-plates. The onset of desensitization was determined using two methods. The first concerned analysis of the time course of decay of the e.p.c.carb. from a peak value during the sustained application of agonist. The second involved a double-perfusion technique in which a 'desensitizing' dose was applied for varying intervals before the application of a second 'test' dose of carbachol. With both methods the development of desensitization at both end-plate types was dependent on carbachol concentration and duration of exposure. At each end-plate type the time course of desensitization onset often exhibited two components; one with a time constant of seconds and a slower component having time constants in the range of tens to hundreds of seconds. The slope of the relationship between carbachol concentration and equilibrium desensitization at slow and twitch fibre end-plates was close to two, suggesting that two molecules of agonist are probably bound during the development of desensitization. However, for all concentrations tested, desensitization developed more rapidly and to a greater extent at twitch fibre end-plates than at slow fibre end-plates. The voltage dependence of the 3 min steady-state desensitization produced by 108 microM-carbachol was very similar (approximately -0.0250 mV-1) at both fibre types.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Alterations in vascular endothelial function in the aorta and mesenteric artery in type II diabetic rats.

We used the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 +/- 17.8 vs. 103.8 +/- 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2- + NO3-) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.

Acetylcholine↗

Urodynamic response of unstable bladder to flavoxate.

Bladder instability provokes frequency, urgency, urge incontinence and enuresis in a great percentage of patients of both sexes, who undergo urodynamic examination when other clinical elements are not in evidence. The presence of bladder contractions of variable entity, even capable of inducing emptying, during filling are accompanied by a strong desire to micturate. Our study includes daily recordings of rhythm and quantity of micturitions and leaks, evaluation of urethral pressure, transurethral cystometry and uroflowmetry. The urethral pressure profile was performed with the technique of Brown and Wickham by infusing at 2 ml/min with 10-Ch catheter, withdrawn at a speed of 15 cm/min. Transurethral cystometry was performed by a continuous infusion at moderate speed (50 ml/min) of an isotonic solution at room temperature in a recumbent patient with two catheters in the bladder. When the contractions of the detrusor appear, we evaluate the pharmacological response to the filling with a myolitic agent (flavoxate) first, and with synthetic anticholinergic (emepronium bromide) after, with the purpose of discriminating the myogenic or neurogenic nature of the alteration and to propose suitable therapy.

Adult↗

The mechanics of esophageal muscle contraction. Evidence of an inotropic effect of gastrin.

To compare the mechanical properties of lower esophageal sphincter (LES) and esophageal circular smooth muscle, force-velocity determinations were made under various physiological conditions. Isotonic and isometric recordings of opossum circular muscle were used to obtain the velocity of shortening and force, respectively, during alterations in: (a) initial muscle length (preload), (b) afterload, (c) calcium concentration, and (d) gastrin I. Muscle contraction was elicited to the neurogenic response at the termination of electrical stimulation. A change in preload (muscle length) altered the peak force (Po) developed during an afterloaded contraction, but had only a minor effect on the maximum velocity of shortening (V max). At the length of optimal tension development, Lo, (preload, 1.5 g), the LES muscle had a V max of 6.1+/-0.2 mm/s and a Po of 17.7+/-0.7 g. The esophageal muscle at its Lo (preload, 2.0 g) had a V max of 6.3+/-0.5 mm/s and a Po of 18.1+/-1.2 g. A decrease in calcium from 2.5 mM to 1.0 mM significantly reduced the V max and Po of all muscle, but an increase in calcium to 5.0 mM increased these parameters only minimally. At a calcium of 1.0 mM, gastrin I increased both V max and Po of all muscle. This inotropic effect of gastrin I occurred at lower concentrations in LES muscle than in muscle from the upper esophagus. The power (force x velocity) and work (force x muscle shortening) of esophageal and LES muscle were calculated from these data. Both the work and power generated during esophageal and LES muscle contraction were determined by: (a) the initial muscle length as produced by the preload, (b) the afterload against which the muscle was contracting, and (c) the contractility of inotropism of the muscle, that is, the force-velocity curve on which the muscle was operating.

Animals↗

Physiologic aspects of relaxation of the myocardium.

To understand relaxation in the intact heart, an appreciation of myocardial relaxation in controlled isometric and isotonic twitches is a prerequisite. Load dependence of myocardial relaxation is manifest as the temporal separation of relaxation in isotonic and isometric twitches, i.e. rapid isotonic lengthening in contrast to slower isometric force decline. Although both isotonic and isometric relaxation modes are governed by the same determinants of crossbridge kinetics (life cycle of individual crossbridges along with regulatory properties of the contractile proteins, and calcium sequestration particularly by the sarcoplasmic reticulum), the contribution of these determinants in controlling onset and rate of relaxation is different in isometric force decline and in isotonic lengthening. In an isometric twitch, cooperative activity will, through a process of force development-induced increased sensitivity of the contractile proteins, upgrade the development and maintenance of force throughout contraction and relaxation. On the other hand, a functional calcium sequestration by the sarcoplasmic reticulum will, in the presence of a reduced effect of cooperative activity in the isotonic twitch, allow for load-induced rapid lengthening. Marked mechanical nonuniformity is observed in intact cardiac muscle. Nonuniformity in cardiac muscle mechanics is usually considered as a nuisance. Uniform behaviour of overall muscle does occur, however, despite or perhaps through nonuniform behaviour of longitudinal muscle segments. A limited but variable degree of nonuniformity therefore probably constitutes an essential property of the heart. A quantitative analysis of nonuniformity in isolated cat papillary muscle is proposed. Pathological considerations require extrapolation of our understanding from isolated muscle relaxation to ventricular relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Correlation between symptom fatigue and muscular fatigue in multiple sclerosis.

The symptom of fatigue is a frequent complaint in multiple sclerosis (MS) patients. Signs of fatigability have been documented in these patients as well. However, correlation with signs of objective fatigue had not been clarified in MS. The aim of this study was to ascertain the existence of muscular fatigue in multiple sclerosis patients, and to find out if there is a correlation between the subjective symptom of fatigue and muscular fatigue. Fifty MS patients and 50 age and sex matched volunteers were studied using isometric and isotonic tests using the dominant hand. Strength was studied in the baseline condition and also after recovery of either an isotonic (experiment A) or isometric effort (experiment B). Maximum strength, strength in relationship to weight, slope of fatigability in 11 consecutive contractions, and strength and duration of a maximum effort were calculated. Fatigue as a symptom was measured using the Fatigue Severity Scale (FSS) and the Fatigue Descriptive Scale (FDS). Non-parametric techniques were used for the statistical analysis. Patients with MS had less isometric and isotonic strength, but the recovery was the same as recovery in the control group. There was a negative linear correlation between the symptom of fatigue and the baseline strength. In conclusion, this study supports the existence of signs of muscular fatigue in MS patients. However, the recovery after exercise is normal. The correlation between the baseline scores in strength and the symptom of fatigue suggest that the same cause (probably pyramidal deficits) may be involved in both of them. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗