Peak Isometric Tension Research Articles

Influence of exercise on excitation-contraction coupling in rat myocardium.

The present studies were conducted to investigate further the mechanisms by which the myocardium adapts to exercise training. Sixty female rats were randomly divided into sedentary control (group C) and trained (group T) groups. Group T was progressively trained for 12 wk. After the rats were killed, left ventricular papillary muscles were mounted in a tissue bath for mechanical studies. Muscles from group T generated greater peak isometric twitch tension per unit cross-sectional area than muscles from group C with [Ca2+]o ranging from 0.25 to 3.5 mM. Analyses of these data indicated that the Km for Ca2+ was not different but that the predicted number of sarcolemmal Ca2+ binding sites was 63% higher in group T. The ATPase activity of the purified cardiac myofibrils was not different between the two groups in the pCa range of 8.53-4.42. Action potentials were recorded with microelectrodes impaled into left ventricular muscle fibers of the subendocardium. Although there was no difference in the resting membrane potential, overshoot, or 90% duration, there was a significant prolongation of the action potential at 0 mV (20.2 +/- 1.0 vs 30.0 +/- 1.3 ms) in group T. These data further support the hypothesis that treadmill exercise enhances cardiac performance by increasing Ca2+ availability to the contractile element. This adaptation is mediated, at least in part, by a sarcolemmal adaptation induced by the exercise paradigm.

Muscle architecture and force-velocity characteristics of cat soleus and medial gastrocnemius: implications for motor control.

1. Isometric and isotonic contractile parameters of the soleus (SOL) and medial gastrocnemius (MG) muscles of seven adult cats were studied. In addition, architectural characteristics of six contralateral pairs of these ankle extensors were determined. 2. The in situ peak isometric tetanic tension developed by the MG at the Achilles tendon is nearly 5 times (9,846 vs 2,125 g) that of the SOL muscle. However, when differences between the MG and SOL in fiber length (2.01 vs 3.66 cm), muscle mass (9.80 vs. 3.31 g), and angle of pinnation (21.4 vs. 6.4 degrees) are considered, the specific tensions of these muscles are similar (approximately 2.3 kg x cm-2). 3. When the effects of muscle architecture are eliminated, the nearly threefold greater maximum isotonic shortening velocity (Vmax) of sarcomeres of the MG (38.2 micron/s) relative to the SOL (13.4 micron/s) is presumably due to intrinsic differences in the biochemical properties of these muscle. However, the Vmax developed by the MG at the Achilles tendon (258.6 mm/s) during a shortening contraction is only 1.5 times that of the SOL (176.3 mm/s) due to the influence of these muscles' specific architectures. 4. Variations in geometrical characteristics of the SOL and MG are consonant with the relative amounts of participation of these muscles during posture, locomotion, and jumping. Posture requires the development of low forces for prolonged periods for which the SOL seems best suited both architecturally and physiologically. The MG, relatively inactive during quiet standing, becomes responsible for a greater percentage of tension and shortening speed during plantar flexion (E3) as gait speeds increase, which is consistent with this muscle's greater tension- and velocity-generating capacity. 5. At high speeds of locomotion (3.0 m/s) and jumping, the shortening velocities developed at the end of E3 (approximately 20-40 ms before paw off) exceed Vmax of the SOL. Consequently, the SOL, although electrically active, cannot contribute to the tensions required to generate the shortening velocities dictated by these movements. 6. These data demonstrate the influence of the differing geometries of the SOL and MG on the roles of these muscles in generating forces at varying velocities, as demanded by the dynamics of the movement.

The relative time course of early changes in mitochondrial function and intracellular pH during hypoxia in the isolated toad ventricle strip.

Changes in the intracellular H+ ion concentration (pHi) and in the oxidation-reduction state of the respiratory chain were measured spectrophotometrically in the isolated ventricle strip from the toad (Bufo marinus). The relative time course of the delta pHi as indicated by changes in light absorption of the pH dye neutral red, cytochrome c, and peak isometric twitch tension were compared during transient hypoxic episodes. The first detectable change in pH occurred 4.5 minutes after the peak twitch tension began to decrease with the onset of hypoxia. The initial decrease in tension and reduction of cytochrome c occurred at a similar time prior to the change in pHi. On reoxygenation, cytochrome c rapidly became oxidized, and the pHi and tension recovered more slowly. During acidification by increasing superfusate PCO2, pHi and tension decreased together, and cytochrome c did not change significantly. Thus, although changes in pHi do affect mechanical performance, these results show that mechanical dysfunction pursuant to hypoxia is not directly attributable to intracellular acidification.

Length-dependent activation of in situ canine skeletal muscle.

This study was designed to assess the contribution of length-dependent activation to the peak isometric twitch tension developed and the maximal rate of tension development (dP/dt) of in situ canine skeletal muscle. Length-developed tension and length-dP/dt relationships were generated for the dog gastrocnemius-plantaris muscle group at three different levels of inotropic state as determined by stimulation frequency. These relationships were then normalized with respect to maximal developed tension and maximal dP/dt and the normalized curves were superimposed for comparison. At progressively shorter muscle lengths the augmentation of tension production by a given increment in inotropic state was greater as measured by either developed tension or dP/dt. Thus, a given change in muscle length produced a greater change in performance in less potentiated muscles. These findings are similar to those from studies of isolated cardiac muscle and illustrate the lack of independence between activational state and muscle length for in situ skeletal muscle.

Structural changes in single muscle fibers after stimulation at a low frequency.

Direct stimulation of single muscle fibers from Xenopus laevis at a frequency of 1 Hz results in a decline of the peak isometric twitch tension after about 200 twitches. Fibers were chemically fixed in glutaraldehyde after a varying number of twitches and at several fatigue levels, and the ultrastructural appearance was compared with that of resting fibers treated by identical fixation methods. No gross structural abnormalities were observed but subtle changes occurred. The mitochondria of stimulated fibers contain granules of normal size and number. The inner crista width is constant but the matrix width is increased on stimulation. These changes would not compromise ATP production. The myofibrils are normal except for a slight swelling in the myosin lattice. The transverse system (T system) and sarcoplasmic reticulum are intact. The minor diameter of the transverse tubule (T tubule) is increased slightly in stimulated fibers. The gap between the T-TC membranes stays constant at about 110 A, but tiny connecting pillars are seen to cross this gap more frequently in stimulated fibers (21 +/- 5% triads) than in resting fibers (8 +/- 6%). In stimulated fibers there is a marked increase in the electron dense content of the terminal cisternae (TC). Inasmuch as the observed structural changes correlate with the number of twitches but not with the fatigue level, it is concluded that TC density and T-TC pillar formation are related to the normal mechanisms of excitation-contraction coupling.

Myocardial energetics during isometric twitch contractions of cat papillary muscle

During myocardial tetanus, when activation is maximum and constant, there is a linear relationship throughout contraction between oxygen consumption (MVo2) and the cumulative product of active tension and time (integral of AT). The goal of this study was to determine the relation of MVo2 to integral of AT during isometric myocardial twitch contractions. Ten right ventricular cat papillary muscles were studied in a flow respirometer. MVo2 was determined during contractions unloaded from Lmax to a slack length at successive 100-ms intervals after stimulation. In contrast to the linear relationship observed during tetanus, MVo2/integral of AT varied during twitch contractions: when the muscles were made slack 100 ms after stimulation MVo2/integral of AT was 389 +/- 51 (SE) (nl of O2/mg of dry muscle)/(N of active tension/mm2.s of active tension). This value was 94 +/- 7 at peak active tension and was constant thereafter. There was a continuous increase in cumulative MVo2 as integral of AT increased; before integral of AT began, MVo2 was 0.41 +/- 0.04 (nl of O2/mg)/contraction at Lmax and 0.22 +/- 0.04 at a slack length; at peak isometric tension MVo2 was 1.84 +/- 0.19; for a complete contraction MVo2 was 2.89 +/- 0.25. These data support two concepts 1) activation energy is small and dependent on initial length and tension; and 2) integral of AT is variably energy dependent throughout the entire isometric twitch contraction.

Dynamic stiffness of rabbit mesotubarium smooth muscle: effect of isometric length.

The dynamic stiffness of mesotubarium smooth muscle from nonpregnant adult rabbits was measured continuously during isometric contraction by applying small (0.5 percent of the muscle length) sinusoidal length perturbations and measuring the amplitude and phase of the resulting tension perturbations. Stiffness during contraction was directly proportional to muscle tension; during relaxation stiffness at all tensions was significantly increased as compared to the values encountered during the rise of tension. Peak isometric tension and dynamic stiffness (determined at a common tension level) both decreased at shorter muscle lengths; the relative falloff in stiffness was significantly less than the tension decrease. Varying levels of muscle activation (obtained by changing stimulus strength and by applying quick releases to active muscle) had little effect on the measured elastic modulus. Comparisons of these results with published data on single-cell contractile properties imply a cellular locus for a portion of the measured stiffness.

The partitioning of altered mechanics in hypertrophied heart muscle between the sarcoplasmic reticulum and the contractile apparatus by means of myothermal measurements.

Cardiac hypertrophy in the rabbit, secondary to pulmonary artery stenosis, results in a decrease in unloaded shortening velocity (Vmax) and maximum rate of isometric force development (dP/dtmax), while the peak isometric twitch tension is unchanged and time to peak tension (TPT) is increased. The principle hypothesis used to explain these results involve 1) slowing of myosin cross bridge movement as reflected in depressed myosin ATPase activity and 2) changes in excitation contraction coupling phenomena resulting in changes in intracellular Ca++ movement. Ca++ and actin activated myosin ATPase from the hypertrophied (H) muscles is depressed by 30%. Total initial heat, tension dependent heat and tension independent heat are depressed in H muscles by 57, 56, and 61% respectively. The rate of tension independent heat production in H preparations is depressed by 66%. From these data it is concluded that 61% of the depression in Vmax could be accounted for by the alteration in myosin with the reminder attributable to changes in EC coupling. Increased TPT can be accounted for by the change in rate of Ca++ flux as indicated by the alterated rate of tension independent heat evolution.

Length-dependent electromechanical coupling in single muscle fibers.

In single muscle fibers from the giant barnacle, a small decrease in muscle length decreases both the calcium activation and the peak isometric tension produced by a constant current stimulus. The effect is most pronounced if the length change immediately precedes the stimulation. In some cases, the decrease in tension with shortening can be accounted for almost entirely by a decrease in calcium release rather than changes in mechanical factors such as filament geometry. During the constant current stimulation the muscle membrane becomes more depolarized at longer muscle lengths than at the shorter muscle lengths. Under voltage clamp conditions, when the membrane potential is kept constant during stimulation, there is little length dependence of calcium release. Thus, the effect of length on calcium release is mediated through a change in membrane properties, rather than an effect on a subsequent step in excitation-contraction coupling. Stretch causes the unstimulated fiber membrane to depolarize by about l mV while release causes the fiber membrane to hyperpolarize by about the same amount. The process causing this change in potential has an equilibrium potential nearly 10 mV hyperpolarized from the resting level. This change in resting membrane potential with length may account for the length dependence of calcium release.

Skeletal muscle fiber regeneration following heterotopic autotransplantation in cats

Whole 3 g extensor digitorum longus (EDL) muscles of cats were autotransplanted. The EDL muscles were either transplanted without denervation prior to transplantation (normal transplants) or denervated 3 to 4 weeks prior to transplantation (pre-denervated transplants). A few peripheral skeletal muscle fibers survived transplantation but most fibers degenerated and then regenerated as the transplant became revascularized. Both normal and pre-denervated muscles regenerated successfully and by 50 days after transplantation fibers which had reinnervated showed high and low myofibrillar ATPase activity. Compared to controls, the smaller mean fiber cross-sectional area of the transplants was due to the large number of small fibers, but some fibers in the transplant were larger than any fibers observed in the controls. Transplants regained 57 percent of the muscle mass of the controls. Contraction and half relaxation times of transplanted muscles were slower than controls, but peak isometric tetanus tension per cm 2 of muscle was nearly normal. Fifty to 170 days after transplantation, muscles showed low oxidative capacity and fatigued rapidly.

Influence of hyperthyroidism on glycerol-extracted cardiac muscle from rabbits

The mechanism responsible for the enhancement of myocardial contractility in hyperthyroidism is unclear. The possibility that this mechanism may involve a direct effect on the contractile proteins was investigated using the glycerol-extracted muscle strip from right ventricular papillary muscles of euthyroid rabbits and rabbits made hyperthyroid by the intraperitoneal injection of 0.25 mg/kg 1-thyroxine for 10 d. Intact papillary muscles from the hyperthyroid rabbits had an enhanced rate of tension development, a decreased time to peak tension, and a slight though insignificant increase in active tension compared to control animals. Maximal isometric contractions were induced in glycerol-extracted cardiac muscle strips from the two animal groups by the addition of 5 mmol/litre ATP and 5 mmol/litre MgCl in a buffer solution containing 0.15 mol/litre Tris-HCl (pH 7.1) at 26 degrees C. Peak isometric tension was increased in glycerinated muscle strips from hyperthyroid rabbits (1.52+/-0.10 vs 1.26 +/-0.13g/mm2), but the differences did not reach statistical significance. However, there was a marked increase in the rate of tension development in the hyperthyroid group (62.5+/-5.4 vs 41.8+/-4.7 mg/mm-2/s, P less than 0.01). This increase in the rate of isometric tension development in both intact and glycerinated muscles from hyperthyroid rabbits may be related to changes in the intrinsic turnover of actomyosin cross-bridge links in this condition. Thus, these findings suggest that thyroid hormone may influence cardiac muscle function by a direct effect on the contractile proteins.

Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock.

There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the "shocked" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from "shocked" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium.

Enhanced contractility during relaxation of cat papillary muscle.

Contractility during relaxation of isometric tension was studied in isolated, electrically driven cat papillary muscle by interpolation of test extrasystoles, all of whichpartially fused with their antecedent (control) contractions, were separated by computer from the fused contractions and then analyzed. The time course of the restitutionof contractility during relaxation was defined by plotting maximal positive dT/dt andtime-to-peak tension of the computer-separated extrasystole versus delay preceding the extrasystole. The dT/dt and time-to-peak tension, which steadily decline with progressive prematurity between contractions, both increase again during late relaxation, become progressively greater still earlier in relaxation, peak shortly after peak isometric tension, and then again decline. This phase of an apparently enhanced contractilityduring relaxation is depressed in low Ca'++ and is transmitted into the postextrasystolic period (in which it is superimposed on the usual postextrasystolic potentiation). The possible contributions of variations in series-elastic component and contractile-element lengths, actionpotential characteristics, and other factors on contractility during relaxation are discussed. It is suggested that enhanced contractility during relaxation may also be related in part to the decay of the intracellular free Ca'++ transient.

Relationships between voltage and tension in sheep cardiac Purkinje fibers.

The two-microelectrode technique of voltage clamping sheep cardiac Purkinje fibers was used to examine the changes in contraction which occur during trains of voltage clamps. (A "train" is defined as a series of voltage clamps delivered at a particular rate, beginning after a rest long enough that the effects of previous stimulation have died away.) Contractions showed striking staircases, or progressive changes in peak isometric tension, during trains. Short clamps, clamps to voltages more negative than --20 or --30 mV, or holding potentials less negative than the resting potential favored negative staircases, while long clamps, clamps to positive voltages, and holding potentials near the resting potential each favored positive staircases. The staircase behavior appeared to be due to changes in the initial rate of recovery of the ability to contract. The changes in staircase behavior as a function of clamp voltage suggested that the relationship between peak tension and clamp voltage should depend on the experimental design. When the steady-state contraction was plotted as a function of clamp voltage, voltage-tension relations like those recently reported for working ventricle were obtained, with a threshold between --30 and --40 mV and a steep relation between tension and voltage. When the first contraction after a rest was plotted, the threshold voltage was more negative, the curve was flatter, and the peak tensions at inside positive voltages were reduced.

Interval dependent inotropic effects in the rat myocardium and the effect of calcium.

Peak isometric tension was measured in isolated rat papillary muscles at different external calcium levels. Rested state contraction (RSC) tension follows a sigmoid curve when plotted against external calcium concentration [Ca]0. Half maximum tension is given at [Ca]0=0.4 mM. Tension declines with increasing stimulation frequency at [Ca]0=2.5 mM. As [Ca]0 is lowered a positive inotropic response to increasing frequency develops over the range of 20–100/min. Similarly post stimulus potentiation can only be elicited at low [Ca]0 levels. The interactions of [Ca]0 and the inotropic effects of stimulation suggest the presence of a pool of releasable Ca, which can be filled passively at high external calcium levels. When [Ca]0 is lower than about 1.5 mM filling becomes stimulus dependent. The identity of phase-plane plots of contraction cycles following potentiation at low [Ca]0 with those of RSC contractions at higher [Ca]0 levels supports the idea that potentiation at low calcium levels operates by the same mechanism as increasing [Ca]0. The rat myocardium has similar properties to that of other species with respect to inotropic effects of stimulation only when the external calcium is reduced to low levels (0.2–0.4 mM).

Histochemical and mechanical properties of the jaw muscles of the cat

The jaw-closing muscles, masseter and temporalis, in the cat reach peak isometric twitch tension in 11–13 msec and half relaxation from peak tension in 10–13 msec. They have high tetanus/twitch ratios and require stimulation at 300–500/sec to reach maximum rate of tension rise. In repeated tetani, some 75% of force is lost relatively rapidly by fatigue. Histochemical examination of serial sections stained for myosin ATPase (MATPase), succinic dehydrogenase (SDH), glyogen and lipid permits the fibers to be allocated to the recognized types A, B and C, with type A predominating. In the jaw muscles types A and C stain more strongly than type B for MATPase but are nevertheless paler than types A and C in gastrocnemius, and cannot be separated by this test alone. Jaw muscle type A fibers are somewhat richer in mitochondria than those of limb muscles. These observations are discussed in relation to the hypothesis that MATPase staining correlates best with speed and oxidative enzyme staining with fatigue resistance. It is concluded that the jaw-closing muscles form an interesting case for correlation of mechanical and histochemical properties because of the dominance of one (fast) fiber type. It is possible that the density of MATPase is not the only factor determining speed in these very fast muscles.

Computer evaluation of peak isometric tension and resting tension of isolated myocardial muscle strip.

Computer evaluation of peak isometric tension and resting tension of isolated myocardial muscle strip.

Myocardial correlates of helium-cold induction and maintenance in hypothermia.

Hypothermia was induced in the golden hamster Mesocricetus auratus, using the helium-cold method. The first group of hamsters was sacrificed immediately after induction to rectal temperature 7 C, a second group was sacrificed after being maintained at a body temperature of 7 C for 18-24 hr, and a third group consisted of unexposed controls. The hearts were excised and the ventricles analyzed for hypoxic damage, glycogen, and catecholamines. In the short-term hypothermic animals, resting tension was increased while peak isometric tension, generated tension after 10 min of anoxic exposure, glycogen, and catecholamines were all reduced. All of the functional parameters recovered in the long-term hypothermic group, while glycogen and catecholamines showed a trend toward recovery. It is concluded that myocardial hypoxia develops during induction into hypothermia when using the helium-cold method. This effect is reversible and hypoxic damage does not increase as the hypothermic exposure is prolonged.

Mathematical representation of the mechanical properties of the heart muscle

Heart muscle has been subjected to many experiments in many laboratories, and many reports are conflicting with each other. To unify the picture, resolve the conflicts, and describe the complex phenomenon in a compact set of equations, a mathematical formulation of the mechanical properties of the heart muscle is presented on the basis of the sliding-element theory and Hill's model. It is proposed that the tensile stress in the parallel and series elements. P and S respectively, can be represented in the form P=(P ∗+ β)e α(L−L ∗) − β S=(S ∗+β)e α(η−η ∗) −β in which L is the muscle length, η is the extension of the series elastic element, α, α , β, β , P ∗ , L ∗ , S ∗ , η ∗ are physiological constants. The total tensile stress τ is the sum of tensile stresses in the parallel and series elements τ=P+S The length is related to the lengths of myosin M, actin C, the ‘insertion’ of actin and myosin Δ, and the series elastic element extension η by the relation L=(M+2C)−Δ+η The contractile element velocity seems best represented by the equation dΔ dt = b(L)sgn S 0λ sin Π 2 t+t 0 t m −S n a(L)+S in which a( L), b( L) are functions of L, S 0 is the peak tensile stress arrived in an isometric contraction at length L, n is an exponent whose value lies between 0 and 1·0, λ sin π (t 0 + t) 2t m is a function describing the active state of the contractile element, t is the time after stimulation, t 0 is a phase shift related to the initiation of active state at stimulation, t m is the half-time to peak activity, λ is an amplitude factor, sgn stands for the ± sign of the quantity S 0λ sin [π. (t + t 0) 2t m ] − S . If the time to reach the peak isometric tension is t ip , and if the level of activity at that instant is arbitrarily set as 1, then 1 λ = sin π 2 t ip+t 0 t m . If experiments are done in the neighborhood of maximum active state, then our equation reduces to the modified Hill's equation υ= dΔ d t = b[S 0−S] n γS 0+S The meaning and justification of these formulas are discussed in the paper. Isotonic and isometric processes, the active state and the relaxation law are analyzed. Necessary corrections to the procedures for measuring the elasticity of series element are discussed; and methods for determining the dependence of series elasticity on the length of the muscle are described.

Effects of experimental heart failure on the capacity of glucagon to augment myocardial contractility and activate adenyl cyclase.

Although glucagon exerts positive inotropic effects in patients with no or mild impairment of cardiac function, similar effects are not consistently observed in patients with chronic heart failure. Accordingly, the inotropic effects of glucagon on papillary muscles from normal cats and cats in which right ventricular failure had been produced for 4-145 days by pulmonary artery banding were compared. At the peak of the concentration-response curve, glucagon increased peak isometric tension (T) in normal muscles from 4.4+/-0.4 to 6.6+/-0.5 g/mm(2) (P <0.001), and maximum rate of tension development (dT/dt) from 16.9+/-0.9 to 25.1+/-1.6 g/sec per mm(2) (P < 0.001). In contrast, glucagon produced no significant increases in T or dT/dt in failure muscles. The percentage increases in T and dT/dt caused by norepinephrine were the same in muscles from normal and failing hearts. Since the cardiac effects of glucagon and norepinephrine may be mediated by adenyl cyclase, responsiveness of adenyl cyclase was determined in particulate fractions of the right ventricle. Glucagon activated adenyl cyclase in normal, but had no effect in failure preparations. Norepinephrine-induced activation of adenyl cyclase, however, was unaltered by failure. Thus, in contrast to norepinephrine, glucagon loses the capacity to augment myocardial contractility and activate adenyl cyclase in hearts derived from cats in chronic failure.