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[The influence of adrenaline on the effects of halothane and enflurane on the myocardium. Papillary muscle of the cat (author's transl)].

In this paper the influence of epinephrine on the isolated papillary muscle has been investigated with respect to the myocardial effects of enflurane and halothane. The contractile properties have been described under isotonic conditions by the parameters "muscle length change", "velocity of shortening and under isometric conditions by the parameters "peak tension" and "maximum rate of tension development". The studies led to the following results: 1. Halothane and enflurane cause a dose-dependent decrease of the contractile properties of the cat papillary muscle. Averaged for all parameters the mycocardial depressant effect of halothane is 2.6 times higher than that of enflurane, referring to equal concentrations. 2. Epinephrine has a positive inotropic effect which is most pronounced under isotonic mode of contraction for "velocity of shortening" and during isometric conditions for "maximum rate of tension development". 3. The positive inotropic effect of epinephrine is partially neutralized by halothane and enflurane. There is, however, evidence that the relative decrease of contractility due to halothane and enflurane is diminished by epinephrine. This finding shows that the myocardial effects of inhalation anaesthetics are overestimated in in-vitro-experiments (because of the lack of exogenous epinephrine) in contrast to experiments with intact animals. As this finding is referring to both halothane and enflurane, there is no specific difference to be found concerning the myocardial effects in comparative studies, including both in-vitro and in-vivo conditions.

Animals↗

In vitro comparison of four tocolytic agents, alone and in combination.

OBJECTIVE: To compare the tocolytic effects of magnesium sulfate, ritodrine, terbutaline, and nifedipine on human myometrial strips. METHODS: Myometrial strips were suspended in organ chambers for isotonic measurements and contracted with KCI. STrips from nonpregnant patients were used to obtain concentration-response curves. Myometrial strips from pregnant uteri were then exposed to the molar concentrations causing 50% relaxation in the nonpregnant tissues. RESULTS: In strips from nonpregnant patients, nifedipine was found to be the most potent tocolytic. Using strips from nonlaboring patients, nifedipine caused relaxation similar to ritodrine, and both were more effective than magnesium sulfate or terbutaline. Combinations were more effective than single agents. These agents were found to be equally less effective in myometrial strips from laboring patients. CONCLUSIONS: Nifedipine, alone or in combination, relaxes myometrial strips more effectively than the other agents studied. Myometrial strips from laboring patients are more resistant to inhibition, with none of the agents being superior.

Adult↗

Mechanically dependent changes in action potentials recorded from the intact frog ventricle.

The wall of the ventricle contracts inhomogeneously during an isovolumic beat of an isolated, intact frog ventricle. Some epicardial segments actually lengthen while the pressure is rising. Almost simultaneously, the early repolarization phase of the monophasic action potential recorded from such a segment is accelerated, compared to the same phase for an isotonic beat in which the segment shortens. Segment lengthening during the isovolumic beat also may be seen during the late repolarization phase when, in contract to the above, it produces an afterdepolarization. These electrical changes disappear when isotonic contraction is restored. Corroborative findings were obtained from microelectrode and insulated gap recordings from isolated frog ventricular strip. Both electrical changes can be seen clearly when the segment is lengthened by intraventricular injections of Ringer's solution. There also is a short transition period toward the end of the action potential plateau when lengthening produces neither depolarization nor repolarization. The accelerated repolarization is manifest as a shortening of the Q-T interval in the ventricular electrogram. In all experimental preparations, the afterdepolarizations reached threshold for a propagated action potential. This mechanism may explain the generation of extrasystoles in myocardial ischemia.

Action Potentials↗

Characterization and work optimization of skeletal muscle as a VAD power source.

Powering a ventricular assist device (VAD) with skeletal muscle in a linear configuration will require the understanding of basic muscle mechanics and efficient use of available power. Accordingly, a mathematical model incorporating aspects of the Hill equation has been developed. This model relates whole muscle length, force, velocity, and time during cyclic contraction to investigate coupling with a hydraulically actuated VAD. Parameters of the model have been determined from in vivo isometric and isotonic measurements of electrically stimulated pig latissimus dorsi with the humerus insertion reattached to a hydraulic loading system. The in vivo results show an exponential passive force-length relationship and active isometric forces increasing from 2 to 8 kgf over a 5 cm change in length. The maximum shortening velocity extrapolated from isotonic data in 85 cm/sec. With the experimentally determined parameters, the model system of differential equations was optimized computationally. Predicted maximum cycle work and corresponding muscle force are nonlinear functions of contraction duration; an increase in duration yields little improvement in work output for longer contraction times. The model helps clarify VAD system design parameters for optimal muscle coupling; for example, the model predicts that operating at maximum instantaneous power does not optimize stroke work.

Animals↗

[Effect of increased mechanical loading on the relation between the contraction of isolated cardiac muscle and the concentration of Ca++ in the perfusate].

The distension of isolated papillary muscles working isotonically or a transition to isometric working entailed an increased sensitivity of the contractile velocity to changes in perfusate Ca++ concentration. After sudden fall in Ca++ concentration, a more rapid decline of the contractile velocity in isometric mode was observed as compared to isotonic mode of working. The similar difference was found in experiments on isolated guinea pig heart working in isovolumic or auxotonic modes, though the rate of Ca++ loss by the heart was the same. The results suggest that an increased mechanical load may diminish the ability of myocardial cells to compensate for the changes in external Ca++.

Animals↗

Inotropic and lusitropic effects of chlorpromazine on rat left ventricular papillary muscle.

The in vitro effects of chlorpromazine on rat cardiac papillary muscle were tested at 10(-6), 10(-5) and 10(-4) M. Mechanical parameters were determined from the contraction and relaxation phases under isotonic and isometric conditions in order to assess contraction, relaxation, contraction-relaxation coupling and load sensitivity of relaxation. The peak power output Emax was determined from the force-velocity relationship. At 10(-6) M, a slight positive inotropic effect was observed, probably related to modifications in cross-bridges kinetics. Negative inotropic effects were observed with 10(-5) and 10(-4) M chlorpromazine. At 10(-5) M, shortening of the isometric relaxation and decrease in R2 = (+dF.dt-1max)/(-dF.dt-1max) suggest that chlorpromazine also diminishes myofilament Ca++ sensitivity. Emax was increased at 10(-6) M (19 +/- 5%, P less than .05), but decreased at 10(-5) M (-28 +/- 10%, P less than .05) and 10(-4) M (-82 +/- 2%, P less than .05). Modifications in the force-velocity relationship at 10(-4) M indicated that lowering myocardial performance by chlorpromazine was associated with a low muscle efficiency from a thermoenergetic point of view. At all concentrations, chlorpromazine impaired the isotonic relaxation and load sensitivity of relaxation. At 10(-4) M, muscle contracture and slowed isometric relaxation were probably due to "calcium overload." These results showed that chlorpromazine finely modulates intrinsic cardiac energetics and mechanics by acting on the sarcoplasmic reticulum, myofilament Ca++ sensitivity and cross-bridges kinetics, according to the level of load and chlorpromazine concentration used.

Animals↗

Effects of prior instruction and anaesthesia on long-latency responses to stretch in the long flexor of the human thumb.

Long-latency (40-80 ms) electromyographic (e.m.g.) responses of the contracting flexor pollicis longus to stretches applied at the thumb-tip, were studied in normal human subjects. Stretches were applied during four classes of contraction: (i) isometric 'hold', in which the subject held a steady isometric contraction; (ii) isometric tracking, in which the subject tracked a steadily rising force target; (iii) isotonic tracking, in which the subject flexed against a constant torque to track a position target; (iv) weight-lifting, in which the subject lifted a weight hung at one end of a lever by pressing the thumb-tip on the other end of the lever. The effects on the responses of prior instructions to 'resist' or to 'let go', and of local anaesthesia of the thumb, were studied. The ability to modify the size of the long-latency e.m.g. response in accordance with prior instruction was variable. All subjects tested could do so during isometric holding contractions, but many could not do so during the other forms of contraction. Local anaesthesia of the thumb significantly reduced the long-latency e.m.g. response in only some subjects, and abolished it in none. The reduction was most reliably seen for isometric force tracking contractions. During thumb anaesthesia in different subjects, there was a significant correlation between the proportional increase in apparent heaviness of an object lifted by thumb flexion and the proportional reduction in the size of the long-latency e.m.g. response to muscle stretch.

Adult↗

Na(+)-independent glucose utilization during Mn(2+)-induced contraction in ileal longitudinal smooth muscle.

In Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium, addition of 5 mM Mn2+ caused a tension about 2.5 x greater than the tonic response induced by 126 mM K+ medium (Ca2+ 2.5 mM, Na+ 0 mM) in ileal muscle. When glycogen was depleted by incubation in a glucose-free, hypertonic 60 mM K+ medium, addition of 5 mM Mn2+ induced only a very weak tension in Ca(2+)-free, isotonic 126 K+ medium. Phlorizin (10(-3) M), a blocker of Na(+)-coupled glucose cotransporter and ouabain (9 x 10(-5) M), an inhibitor of Na+, K(+)-ATPase, failed to inhibit the tension elicited by 5 mM Mn2+ in a Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium. Mn2+ was accumulated in the intracellular compartment in a Ca(2+)- and Na(+)-deficient, isotonic 126 mM K+ medium. The tissue ATP concentration was significantly reduced in a Na(+)-deficient 126 mM K+ medium. However, it recovered almost completely when 5 mM Mn2+ was added to the isotonic 126 mM K+ medium. These results suggest that the Mn(2+)-induced contraction in depolarized ileal longitudinal muscle in Na(+)-deficient medium may be maintained by a glucose transport which is not dependent on Na+ and insensitive to phlorizin.

Adenosine Triphosphate↗

Induced potential model for muscular contraction mechanism, including two attached states of myosin head.

The model for myosin head motion along an actin filament as proposed by Mitsui & Chiba [(1996). J. theor. Biol. 182, 147-159] is here modified so that it can explain the isometric tension and isotonic velocity transients having the same parameter values as the stationary filament sliding. The modified model differs in that a myosin head forms a complex with two actin molecules in an actin filament and has two attached states in the complex instead of three. Thus an incremental step in the myosin head motion is equal to the F-actin monomer repeat (5.46 nm). Muscle properties concerning the stationary filament sliding are calculated with new parameters in a manner similar to that of Mitsui-Chiba, with the results being qualitatively similar to theirs. In studying the transient phenomena, a quantitative expression is given for the potential energy of the myosin head in the complex, and two rate constants are applied to the kinetics of the head. The time course of tension recovery after a quick length change is determined by calculating the statistical distribution of the head in the two attached states, which conforms to experimental observations by Ford et al. [(1977). J. Physiol. 269, 441-515]. The tension variations T1/T0 and T2/T0 calculated with parameters determined from the analysis of stationary filament slidings are in fairly good agreement with the experimental data by Ford et al. The model suggests that a large fluctuation exists in the relative position between the actin and myosin filaments even when the load on a muscle is kept constant. Taking this fluctuation into account explains the characteristics of the isotonic velocity transient observed by Civan & Podolsky.

Actins↗

The effect of sudden stretches on length-tension-and force-velocity relations of mammalian cardiac muscle.

In the isotonically beating cat papillary muscle, a sudden augmentation of the preload initiates a visco-elastic strain retardation, in the course of which the preparations show a marked increase in their isotonic mechanogram amplitudes. It is preceded in the first seconds by a short-term decline. These effects correspond well with the phenomena of stress relaxation. When applying these post-stretch phenomena to the length-tension diagram, it is shown that the isometric and isotonic length-tension curves are significantly shifted to greater distances with respect to the resting length-tension curve, involving even a doubling of the myocardial working capacity in certain cases. Stretch-induced alterations in Vmax which were obtained from damped quick-releases, initiated during isometric contractions are almost negligible. On the other hand Vmax obtained from quick-releases which were started immediately after the onset of isotonic contractions are strongly affected by sudden stretches. The stair-like decline of the mechanograms in the initial phase of relaxation or retardation is assumed to be mediated by a stretch-induced alteration in the time course of the action potential. The additional reduction in myocardial performance superimposed on this, is consistent with the hypothesis of a stretch-induced transient inactivation or a delayed activation of contractile interaction sites.

Action Potentials↗

Relative displacements in muscle and tendon during human arm movements.

1. X-ray, cine and video recordings were made of the movement of radio-opaque markers injected into the musculo-tendinous junctions of biceps brachii muscle. 2. In strong isometric contractions, the distal tendon of the long head of biceps lengthened by about 2% of its estimated rest length. 3. During voluntary isotonic elbow flexion-extension movements at frequencies up to 5.5 Hz there was no detectable phase shift between intramuscular and joint displacements. 4. In the fastest alternating movements (5.5-6.7 Hz) small phase advances developed in the muscle. 5. We conclude that human tendons do stretch during muscle contraction, but not enough to cause intramuscular phase reversals in rapid unloaded movements. This in turn means that muscle spindles shorten and lengthen virtually in phase with joint movements under most conditions.

Arm↗

Dynamic actin interaction of cross-bridges during force generation: implications for cross-bridge action in muscle.

The force response of Ca(2+)-activated, permeabilized segments of rabbit psoas muscle fibers to stretches and releases was studied. These length changes were imposed (i) during isometric steady state contraction, (ii) as a restretch at the end of a ramp-shaped prerelease, and (iii) during isotonic steady state shortening. The speed of the stretches/releases was varied between about 10 and 10(5) (nm/half-sarcomere)/s. At physiological ionic strength and at low temperature (5 degrees C), the force response to stretches apparently is neither affected by cross-bridges that occupy weak-binding states nor by redistribution among various attached force-generating states. Plots of force vs. imposed length change ("T-plots") and plots of apparent fiber stiffness vs. speed of the imposed length change ("stiffness-speed relations") recorded under all these conditions suggest that cross-bridges, even during force-generation, dissociate and reassociate from and to actin on a time scale that is fast compared to active cross-bridge cycling (> 50- 1000s-1 vs. 1-10s-1). This rapid dissociation/reassociation of force-generating cross-bridges may provide a mechanism to account for the unexpectedly low ATPase activity during high-speed shortening and for filament sliding exceeding 10-20nm while a cross-bridge passes through the force-generating states.

Actins↗

Isometric relaxation of isolated diaphragm muscle: influence of load, length, time, and stimulation.

Determinants of the isometric relaxation rate were investigated in isolated rat diaphragm (n = 30). We tested the hypothesis that these determinants could include loading conditions, namely preload and afterload; abrupt changes in load during the contraction phase; stimulation conditions; and time. Two relaxation sequences were studied. When isometric relaxation occurred at initial muscle length (isotonic-isometric sequence), an increase in total load (P) accelerated the negative peak rate of tension decline (-dP/dtmax). Variations in initial length, stimulation, and onset of relaxation did not modify the -dP/dtmax vs. afterload relationship. When isometric relaxation was analyzed after -dP/dtmax, for a given afterload level the instantaneous rate of tension decline (-dP/dt) was a unique function of instantaneous tension, regardless of previous loading conditions, stimulation mode, or time. When the isometric relaxation occurred at end-shortening muscle length (isometric-isotonic sequence), the -dP/dtmax vs. P relationship was flat. The rate of tension decay, as attested by either -dP/dtmax or instantaneous -dP/dt vs. instantaneous tension phase plane, differed markedly depending on stimulation conditions. Thus the regulation of isometric relaxation rate differed according to the relaxation sequence. In muscle isometrically relaxing at initial muscle length, peak isometric relaxation rate was mainly determined by afterload. Conversely, in muscle isometrically relaxing at end-shortening length, isometric relaxation rate was highly dependent on the level of activation and was independent of preload and afterload.

Animals↗

Optimal shortening velocity (V/Vmax) of skeletal muscle during cyclical contractions: length-force effects and velocity-dependent activation and deactivation.

The force-velocity relationship has frequently been used to predict the shortening velocity that muscles should use to generate maximal net power output. Such predictions ignore other well-characterized intrinsic properties of the muscle, such as the length-force relationship and the kinetics of activation and deactivation (relaxation). We examined the effects of relative shortening velocity on the maximum net power output (over the entire cycle) of mouse soleus muscle, using sawtooth strain trajectories over a range of cycle frequencies. The strain trajectory was varied such that the proportion of the cycle spent shortening was 25, 50 or 75 % of the total cycle duration. A peak isotonic power output of 167 W kg-1 was obtained at a relative shortening velocity (V/Vmax) of 0.22. Over the range of cyclical contractions studied, the optimal V/Vmax for power production ranged almost fourfold from 0.075 to 0.30, with a maximum net power output of 94 W kg-1. The net power output increased as the proportion of the cycle spent shortening increased. Under conditions where the strain amplitude was high (i.e. low cycle frequencies and strain trajectories where the proportion of time spent shortening was greater than that spent lengthening), the effects of the length-force relationship reduced the optimal V/Vmax below that predicted from the force-velocity curve. At high cycle frequencies and also for strain trajectories with brief shortening periods, higher rates of activation and deactivation with increased strain rate shifted the optimal V/Vmax above that predicted from the force-velocity relationship. Thus, the force-velocity relationship alone does not accurately predict the optimal V/Vmax for maximum power production in muscles that operate over a wide range of conditions (e.g. red muscle of fish). The change in the rates of activation and deactivation with increasing velocity of stretch and shortening, respectively, made it difficult to model force accurately on the basis of the force-velocity and length-force relationships and isometric activation and deactivation kinetics. The discrepancies between the modelled and measured forces were largest at high cycle frequencies.

Animals↗

Relationships between isometric and isotonic mechanical parameters and cross-bridge kinetics.

1. Isometric and isotonic measures have been widely used both to characterize muscular contraction in striated muscle and to compare the mechanical properties of striated muscle types for a wide variety of species. The interrelationship of these measures and their interpretation, in terms of underlying cross-bridge mechanisms, requires clarification. 2. We demonstrate that a strain-dependent three-state model can simulate these isometric and isotonic mechanics and offer a unified explanation for these mechanics in terms of cross-bridge kinetics. 3. Our exploration reveals the partial view each individual measure of mechanics provides and emphasizes the complementary insights the various isometric and isotonic measures give of the underlying cross-bridge kinetics.

Adrenergic beta-Agonists↗