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Comparative in vitro and in vivo studies on the effects of tricyclic antidepressants on myocardial contractility.

The effects of the similarily structured antidepressant drugs imipramine and dimetacrine and their demethylated derivatives on myocardial performance were studied in vitro on 42 right ventricular papillary muscles of cats. The hemodynamic effects of intravenous administration of 22 mg of free base imipramine and dimetacrine were investigated in 12 patients with coronary disease. The results of the in vitro studies show that imipramine greater than dimetacrine greater than desmethyl compounds have a marked dose-dependent negative inotropic effect on all parameters of myocardial contractility, i.e., afterloaded isotonic contractions (delta L), dL/dtmax, dL/dtmin,dT/dt. The hemodynamic investigations indicate that imipramine greater than dimetacrine induces a significant increase in end-diastolic left ventricular pressure. Both drugs increase mean arterial blood pressure, correlated to a peripheral vasoconstriction and corresponding to an increase on the plasma level of catecholamines. It is concluded that both effects of these antidepressant drugs (reduction of myocardial performance and an increase in the plasma level of catecholamines) must be considered a risk in patients predisposed to myocardial failure.

Acridines↗

[Transformation of the strength characteristics and work capacity of antagonistic muscles during rabbit postnatal ontogenesis].

In the rabbit muscles-antagonists in situ, the dependence of work (A) of isotonic contraction of the load (P) was studied in different age periods. For the range of loads 1.5 - Popt greater than or equal to P greater than or equal to 0.5 - Popt, the results were found to be satisfactorily approximated by the equation A = A opt = a - /Popt - P/2, where Aopt, Popt, and a are constants. The experiments revealed that the ratio Aopt. m. gastrocnemius/Aopt. m. tibialis anterior sharply increases during realization of the standing posture (16-18 days) and then drops at the grown-up age. Similar age changes were revealed for the Popt parameters ratio of the same muscles. At the same time, the respective ratio of the a parameters of the muscles under study drops sharply by the 16-18th day age, practically remaining the same afterwards. The obtained changes of the strength parameters and working ability of skeletal muscles in the course of postnatal ontogenesis are regarded from the standpoint of peculiarities of the skeletal muscles functioning at different age periods and with regard to ecological peculiarities of individual development of rabbits.

Animals↗

Activity in three parts of the quadriceps recorded isometrically at two different knee angles and during a functional exercise.

The purpose of this study was to evaluate individual differences in three parts of the quadriceps activated isometrically at 60 degrees and 90 degrees of knee flexion, and during a functional activity involving both concentric and eccentric muscle work. Surface EMG amplitudes were therefore recorded from oblique parts of vastus medialis (VMO) and vastus lateralis (VLO) and from rectus femoris (RF). VMO and VLO showed less activation at 60 degrees than at 90 degrees, but in RF there was no difference between the two angles. In the second experiment, where 11 subjects stepped on and off a stool; these amplitudes were compared with those from a maximal isometric voluntary contraction at 90 degrees of knee flexion. For VMO & VLO the normalised peak amplitude in stepping up was 1.41 +/- 0.12, & 1.46 +/- 0.15 respectively, showing that higher activity is necessary during concentric contractions. These two results suggest that the motor control of VMO/VLO may be different from the bulk of quadriceps. Our findings have implications for patellofemoral function.

Adult↗

Measurement of torque of trunk flexors at different velocities.

The purpose of this study was to determine the test-retest reliability of recording isometric and isokinetic torque of the trunk flexors and to examine the effect of velocity on the torque curves. Thirty healthy subjects were tested on two occasions for isometric torque of trunk flexion at four angles and eccentric and concentric torque at three velocities. Two subjects repeated these tests in the passive mode to determine the torque produced by the trunk when there was no active flexion effort. Intraclass correlation coefficients were above 0.85 for all isometric and isokinetic measures. Standard errors of measurement ranged from 6.9 to 19.5 Nm. Student t-tests indicated no significant differences between occasions for all outcome measures. Examination of passive and active torque curves indicated that the torque produced by the mass of the trunk increased with increasing velocity. It is concluded that both isometric and isokinetic testing of the trunk flexors are reliable, but that testing at higher velocities may not provide a valid measure of muscle performance.

Abdominal Muscles↗

[Spontaneous activity of the passive muscle spindles of the cat triceps surae].

In a slack deeferented m. triceps surae about 45% of 400 stretch receptors under study have a spontaneous discharge. The following facts indicated that some intrafusal fibres in the slack muscles are presumably in the prestretch state: 1) the isotonic contraction of the muscle diminished or abolished the spontaneous discharge; 2) at the beginning of the stretch of the slack muscle the initial slowing in the discharge frequency of the unit sometimes appeared; this slowing did not depend on the type of unit and occured in a unit among many others in the same preparation and under the same conditions of experiment; 3) the dynamic thresholds of spontaneously discharging units were lower than that of units without spontaneous discharge. It is suggested that a static stretch occurs in some muscle spindles, if the distance between two points of big fibres insertion on extrafusal fibres or tendon fascicules is longer than the length of intrafusal fibres. The initial slowing at the beginning of stretch is presumably due to viscous damping forces which must be higher in more viscous extrafusal fibres in comparison to that of intrafusal fibres.

Action Potentials↗

Neuromuscular effects of three training methods in ageing women.

AIM: The present study aimed to compare the effects of 3 strength development methods on muscular mass and muscular strength in healthy ageing women. METHODS: Thirty-two healthy women, 62 to 75 years old were randomised into 3 groups. The 3 groups performed 4 sessions a week of strength development for 6 weeks. The 1(st) group (SC) climbed up and down 300 stairs per session. The 2(nd) group (ES) followed an electrostimulation programme on the quadriceps muscles. The 3(rd) group (SC+ES) combined stair climbing with electrostimulation. Before and after the 3 programmes, the muscular mass of the leg was assessed using a biphotonic absorptiometry machine. Isometric (angle 20 degrees and 100 degrees ) and isokinetic (60 degrees /s and 240 degrees /s) knee extension torque was measured using an isokinetic dynamometer. RESULTS: None of the programmes changed the muscular mass. All 3 groups increased isometric (angle 20 degrees, p<0.001; angle 100 degrees, p<0.003) and isokinetic (60 degrees /s, p<0.0001; 240 degrees /s, p<0.0001) knee extension torque. None of the programmes appeared more efficient than the others for muscular mass or muscular strength. CONCLUSION: Six weeks of activity (SC, ES or SC+ES) improved the isometric and dynamic muscular strength in ageing healthy women. However, this period was too short to change the muscular mass. None of the activities presented a real advantage over the others in ageing women.

Age Factors↗

Mechanomyographic time and frequency domain responses of the vastus medialis muscle during submaximal to maximal isometric and isokinetic muscle actions.

The purpose of this study was to examine the patterns for the mechanomyographic (MMG) amplitude and mean power frequency (MPF) versus torque relationships during isometric and isokinetic muscle actions. Ten adults (mean age +/- SD = 22 +/- 1 y) volunteered to perform isometric and isokinetic leg extension muscle actions at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100% of peak torque on a Cybex II dynamometer. A piezoelectric crystal contact sensor was placed on the vastus medialis to detect the MMG signal. Regression analyses indicated that for the isometric muscle actions, the relationships for MMG amplitude (R2 = 0.998) and MPF (R2 = 0.987) versus torque were cubic. For the isokinetic muscle actions, the relationships for MMG amplitude (r2 = 0.927) and MPF (r2 = 0.769) versus torque were linear. The different patterns for MMG amplitude and frequency may reflect differences in the motor control strategies that modulate torque production for isometric versus dynamic muscle actions.

Adult↗

Developmental changes in response of dog isolated ventricular myocardium to norepinephrine.

There are maturational changes of myocardial function and response to inotropic agents. Because of incomplete myocardial sympathetic innervation, neonatal myocardium may be more sensitive to norepinephrine than is adult myocardium. We tested this hypothesis by using isolated trabecular muscle from two groups of puppies and from adult dogs. The muscles were exposed to norepinephrine at concentrations of 1 x 10(-10) to 1 x 10(-4) M, and indices of isometric and isotonic contraction were measured. Active tension and maximum rate of contraction increased in all age groups with norepinephrine. Adult dogs were more sensitive than puppies to the arrhythmogenic effect of norepinephrine. Although there was no strictly significant difference statistically, there appeared to be an age-related increase in the dose at which 50% of the maximum effect of the drug was achieved (ED50). Total contraction time, time to peak tension, and relaxation time decreased with increasing concentrations of norepinephrine in older puppies and in adults but not in newborn puppies. Thus, there are significant age-related differences in response to norepinephrine.

Journal Article↗

Effects of protopine on intracellular calcium and the PKC activity of rat aorta smooth muscle.

We have previously shown that the vasodilator effect of protopine (Pro) on rabbit aorta is related to the elevations of cAMP and cGMP. In the present study, the vasodilator mechanisms of Pro were further explored by recording the isotonic contraction of the rat aortic strips, detecting directly the intracellular free Ca(2+) concentration ([Ca(2+)](i)) with Fura-2/AM loaded vascular smooth muscle cells (VSMCs) of rat aorta, and determining the activity of protein kinase C (PKC) in rat aortic tissue with radioactive isotope gamma-32P -ATP-catalyzing assay. By recording the aortic strips contraction induced by noradrenaline (NA) and high potassium (K(+)), Pro shifted nonparallelly the concentration-response curves of NA and high K(+) to right, in which the maximal response was depressed in the presence of Pro (30 and 100 micromol/L), and the values of pD'(2) were 3.70-/+0.25 and 3.97-/+0.15 for NA and high K(+), respectively. In the Fura-2/AM loaded VSMCs, Pro (50 and 100 micromol/L) could not produce any significant change on the resting [Ca(2+)](i), but significantly decreased the [Ca(2+)](i) elevated by NA and high K(+). Pro (30 and 100 micromol/L) had no significant effect on the activity of the cytosolic and membrane PKC in the aortic strips inpretreated by NA. However, in the aortic strips pretreated by NA, the activity of membrane PKC was significantly increased and the activity of cytosolic PKC tended to be decreased by Pro, while the activity of total PKC did not change. These results suggest that Pro seems to promote the translocation of PKC from the cytosol to the membrane in the presence of NA, its vasodilator effect may be the comprehensive result of its decreasing effect on the [Ca(2+)](i) and the increasing effect on cAMP and cGMP, as well as its influence on the PKC.

Animals↗

Fluorometric and myothermic studies of cardiac energetics.

Energy production during isometric and isotonic contractions of cardiac muscle has been studied using the isolated papillary muscle of the rabbit at room temperature. Muscles were mounted on thermopiles to record heat production associated with small numbers of contractions and then were mounted in an organ bath for fluorometric recording of the level of reduction of mitochondrial NAD. After each twitch there was a decrease in the level of fluorescence followed by an exponential return to the resting level, or further decreases after subsequent twitches. The fluorescence-time integral (integral delta Fl-dt), or area enclosed by a fluorometric transient during and after a series of twitches, was found to vary in magnitude in a manner similar to the magnitude of the total heat production when the mechanical conditions of contraction were altered by varying the load. The influence of the metabolic state of the muscle was also studied by using either glucose or sodium pyruvate as the exogenous substrates in the bathing medium. When pyruvate was substituted for glucose, maximum external work, maximum isometric force, and maximum mechanical efficiency were all increased. The kinetics of oxidative recovery metabolism, either measured fluorometrically or derived from the heat production, was accelerated when pyruvate replaced glucose.

Animals↗

The effect of orexins on intestinal motility in vitro in fed and fasted rats.

Orexin-A and -B (OXA, OXB) are peptides involved in many gastrointestinal (GI) functions, including motility. Orexins, their precursors and receptors are present in the GI tract. The expression of orexins increases in the hypothalamus and gastrointestinal tract in response to fasting. We have examined the effect of OXA and OXB on GI motility in vitro in fed and fasted rats. The intestinal segments were mounted in chambers filled with Krebs solution. Isotonic contractions were measured in response to acetylcholine (10(-5) M), electric field stimulation (EFS), and orexins (10(-9)-10(-7) M) alone or in the presence of orexin-1 type receptor antagonist, SB- 334867 (10(-5) M), tetrodotoxin (TTX) 10(-6) M, or atropine (10(-5) M). Orexins caused a dose-dependent increase of intestinal segment contractions with a more pronounced effect of OXB over OXA. Fasting did not influence orexin-induced responses. Incubation with SB-334867 led to a marked decrease in orexin-induced contractions in OXA-treated segments, while those of OXB were not affected. Atropine diminished contractions only in fasted animals, while TTX led to a decreased response to orexins in both groups. The results show that OXB is predominant in inducing gut motility response, that the effect of orexins is not fully dependent on cholinergic and Na(+) transmissions, and that involvement of other transmitters is possible.

Animals↗

A comparison of contractile properties in the preferred and nonpreferred leg in a mixed sample of dystrophic patients.

No study of how muscle contractile function is related to limb preference in human muscular dystrophy is presently available. The purpose of this study was to determine if the ankle plantarflexor (PF) and dorsiflexor (DF) muscle groups of the preferred leg are more or less affected than the nonpreferred one in a mixed sample of myotonic and limb-girdle patients. Measurements of lower limb preference were made as well as of PF and DF evoked and voluntary contractile responses. Isometric contractile properties and peak values for torque production during maximum isometric twitch and voluntary contractions were measured. No significant difference was found in terms of contractile properties between the preferred and nonpreferred leg for both DF and PF muscle groups, except for the large PF twitch torque observed in the nonpreferred side (P less than 0.05). These results, however, reveal a clear tendency for both muscle groups on the preferred side to be weaker than those on the nonpreferred side. This last finding, in conjunction with the equally if not presumably stronger PF/DF muscles on the preferred leg of healthy adult subjects, would suggest that the equivalent bilateral muscle force observed in the present study may be interpreted as giving support to the hypothesis that overwork or overuse of dystrophic muscles may be harmful in weakening the musculature.

Female↗

[Effects of calcium ion on contractile response of guinea-pig gallbladder muscle strip to agonists].

The effects of calcium ion on the contractile response of gallbladder muscle strip (GBMS) in guinea pigs to acetylcholine, carbachol and caerulein were investigated by method of isotonic contraction and by RIA of cGMP and cAMP in the tissue. It was shown that the contractile response of GBMS to these agonists was stronger in Krebs solution than that in the calcium-free solution. In calcium-free solution, EDTA-zero calcium solution or verapamil-Krebs solution, the contractile response of GBMD was decreased to about 30% of the control (P less than 0.01). Verapamil significantly decreased carbachol induced enhancement of cGMP and cAMP of gallbladder tissue (P less than 0.01 or 0.05). The results suggest that both extra-and intra- cellular calcium take part in the contractile response of GBMS to agonists.

Acetylcholine↗

A physiological comparison of female body builders and power lifters.

Ten female body builders (FBB) (X age +/- SD = 30.40 +/- 8.22 years) and ten female power lifters (FPL) (X age +/- SD = 25.20 +/- 6.01 years) were studied to determine group differences in body composition, strength and anaerobic characteristics. All subjects had been training a minimum of two years and twelve of the subjects had competed nationally while the remainder had participated in regional or local events. Measures of body build and body composition were obtained via hydrostatic weighing, skinfolds (sum of 7), circumferences (sum of 13) and diameters (sum of 9). Flexion and extension strength of the dominant forearm and leg were measured with a Cybex II dynamometer at 60 degrees/second. Anaerobic power and capacity were determined using the Wingate Anaerobic Test. Independent t-tests indicated the FPL had significantly greater body weight (X +/- SD = 68.60 +/- 3.60 vs 56.47 +/- 0.85 kg), relative fat (21.47 +/- 1.29 vs 13.51 +/- 1.46%), sum of skinfolds (120.76 +/- 7.55 vs 71.46 +/- 7.02 mm), sum of diameters (177.57 +/- 2.97 vs 168.17 +/- 2.55 cm), and sum of circumferences (594.93 +/- 13.10 vs 551.24 +/- 3.17). No significant differences were found for fat-free weight, strength or anaerobic power and capacity. These results demonstrate subtle but specific differences between well-trained FBB and FPL reflecting the leaner physiques and smaller skeletal structures of the FBB necessary for the definition and symmetry demanded by the sport. The lack of differences in strength and anaerobic characteristics reflect the similarity of the groups in basic training techniques.

Adult↗

Structure of the glomerular mesangium: a biomechanical interpretation.

This paper summarizes our current knowledge of the structural details and probable functional significance of the system of contractile filaments in the glomerular mesangium. The description is based mainly on studies of superficial glomeruli of the rat kidney. The contractile apparatus of mesangial cells consists of microfilament bundles located predominantly within mesangial cell processes. The thickest microfilament bundles occur in the juxtacapillary mesangial cell processes, which directly abut the glomerular capillaries. The effector structure of mesangial cell contractility is the GBM. Mesangial cell processes are connected to the GBM either directly or through the interposition of extracellular microfibrils. In general, the contractile system of the mesangium interconnects opposing parts of the GBM. This arrangement is particularly obvious in the juxtacapillary processes, which underlie a mechanical connection between the GBM at the two opposing mesangial angles of a single capillary. The geometry and structural composition of the contractile apparatus of the mesangium indeed suggest a static rather than a dynamic function. In conjunction with the GBM, the mesangial contractile apparatus seems capable of supporting sufficient wall tension to counteract the distending forces acting across the capillary walls; the apparatus also seems capable of directly balancing the distending forces on the perimesangial walls. Assuming that mesangial cells are capable of isotonic contractions, the effect of such a contraction on capillary diameter and, consequently, on filtration area would be small.

Actin Cytoskeleton↗

Ultrastructural organization of contractile proteins in rat glomerular mesangial cells.

Glomerular mesangial cells of the rat kidney contain actin, nonmuscle myosin, tropomyosin, and the muscular Z-line protein, alpha-actinin. This was shown for actin, myosin, and alpha-actinin by immunoblotting as well as by immunoelectron microscopy. Tropomyosin was localized in mesangial cells by immunofluorescence. In cultured mesangial cells, actin, myosin, and alpha-actinin constitute a considerable amount of the total cellular protein contents. In mesangial cells in situ actin, myosin and alpha-actinin were found to be colocalized within conspicuous microfilament bundles that traverse the cell body or major processes in various directions and project into either the tonguelike pericapillary processes, which run toward mesangial angles, or into the microvilluslike lateral extensions that abut on the perimesangial portion of the glomerular basement membrane (GBM). Thereby, the GBM of opposing mesangial angles as well as of opposing portions of the perimesangial GBM are regularly interconnected by filament bundles within mesangial cells that contain actin, myosin, and alpha-actinin. The authors suggest that the major function of actin-, myosin-, and alpha-actinin-containing filament bundles in mesangial cells is to create an isometric tension (or minute isotonic contractions) to counteract the distending forces of the rather high intracapillary hydraulic pressure and its resulting pressure gradients across the capillary wall and across the perimesangial GBM.

Animals↗

Heart muscle: mathematical modelling of the mechanical activity and modelling of mechanochemical uncoupling.

A mechanical model of heart muscle is proposed which includes rheological equations and equations for Ca-troponin interaction, for the dependences of the number of myosin cross-bridges on the length of sarcomere and on the speed of motion. The main assumption of the model is the dependence of the troponin affinity to calcium ions on the number of myosin cross-bridges attached. The model successfully imitates isometric and isotonic contractions, the "length-force" relationships, load-dependent relaxation, and the group of mechanical phenomena known as mechanochemical uncoupling.

Actins↗