Peak Isometric Tension Research Articles

High tension in sarcomeres hinders myocardial relaxation: A computational study.

Experiments have shown that the relaxation phase of cardiac sarcomeres during an isometric twitch is prolonged in muscles that reached a higher peak tension. However, the mechanism is not completely understood. We hypothesize that the binding of calcium to troponin is enhanced by the tension in the thin filament, thus contributing to the prolongation of contraction upon higher peak tension generation. To test this hypothesis, we developed a computational model of sarcomere mechanics that incorporates tension-dependence of calcium binding. The model was used to simulate isometric twitch experiments with time dependency in the form of a two-state cross-bridge cycle model and a transient intracellular calcium concentration. In the simulations, peak isometric twitch tension appeared to increase linearly by 51.1 KPa with sarcomere length from 1.9 μm to 2.2 μm. Experiments showed an increase of 47.3 KPa over the same range of sarcomere lengths. The duration of the twitch also increased with both sarcomere length and peak intracellular calcium concentration, likely to be induced by the inherently coupled increase of the peak tension in the thin filament. In the model simulations, the time to 50% relaxation (tR50) increased over the range of sarcomere lengths from 1.9 μm to 2.2 μm by 0.11s, comparable to the increased duration of 0.12s shown in experiments. Model simulated tR50 increased by 0.12s over the range of peak intracellular calcium concentrations from 0.87 μM to 1.45 μM. Our simulation results suggest that the prolongation of contraction at higher tension is a result of the tighter binding of Ca2+ to troponin in areas under higher tension, thus delaying the deactivation of the troponin.

Timing and magnitude of systolic stretch affect myofilament activation and mechanical work.

Dyssynchronous activation of the heart leads to abnormal regional systolic stretch. In vivo studies have suggested that the timing of systolic stretch can affect regional tension and external work development. In the present study, we measured the direct effects of systolic stretch timing on the magnitude of tension and external work development in isolated murine right ventricular papillary muscles. A servomotor was used to impose precisely timed stretches relative to electrical activation while a force transducer measured force output and strain was monitored using a charge-couple device camera and topical markers. Stretches taking place during peak intracellular Ca(2+) statistically increased peak tension up to 270%, whereas external work due to stretches in this interval reached values of 500 J/m. An experimental analysis showed that time-varying elastance overestimated peak tension by 100% for stretches occurring after peak isometric tension. The addition of the force-velocity relation explained some effects of stretches occurring before the peak of the Ca(2+) transient but had no effect in later stretches. An estimate of transient deactivation was measured by performing quick stretches to dissociate cross-bridges. The timing of transient deactivation explained the remaining differences between the model and experiment. These results suggest that stretch near the start of cardiac tension development substantially increases twitch tension and mechanical work production, whereas late stretches decrease external work. While the increased work can mostly be explained by the time-varying elastance of cardiac muscle, the decreased work in muscles stretched after the peak of the Ca(2+) transient is largely due to myofilament deactivation.

E-C Coupling Alterations and Spontaneous Activity in Mice Carrying Cardiac Troponin T Mutations

Ca2+ handling abnormalities are an early-onset pathogenic element in HCM. Here we characterize pro-arrhythmogenic changes in E-C coupling that occur in intact trabeculae and cardiomyocytes from cTnT mutant mouse models of HCM (R92Q, E163R and Δ160E) and test the effects of specific pharmacological interventions. Compared to WT, R92Q trabeculae ([Ca2+]o 2 mM, 30°C) showed (i) preserved peak isometric twitch tension and prolonged relaxation kinetics associated to decreased SERCA levels, (ii) faster mechanical restitution, further accelerated by isoproterenol (Iso) 100nM, (iii) decreased Ca2+-recirculation fraction markedly increased by Iso (iv) frequent after-contractions or regular spontaneous beats during stimulation pauses that increased in response to Iso. Compared to WT, R92Q cardiomyocytesshowed (i) prolonged action potentials associated with ionic current remodeling, (ii) slower rate of Ca2+transient decay, (iii) elevated diastolic [Ca2+]i, (iv) spontaneous Ca2+ waves during stimulation pauses. In R92Q preparations, the late-Na+ current blocker Ranolazine (Ran 10 μM) (i) reduced the rate of spontaneous beats and spontaneous Ca2+ waves, (ii) hastened Ca2+ transient kinetics and reduced diastolic Ca2+, (iii) reduced and reversed the acceleration of mechanical restitution and the increase in Ca2+ recirculation fraction induced by Iso.Compared to R92Q, occurrence of spontaneous contractions was similar in E163R but less pronounced in Δ160E. Iso and Ran showed similar effects in all three mouse models, in spite of some quantitative differences. The results are consistent with those recently reported in human HCM myocytes (Coppini et al, Circulation 2013) and suggest that remodeling and dysfunction of NCX and RyR2 contribute to the pro-arrhythmogenic E-C coupling abnormalities observed in HCM.

Myocardial Rac1 Exhibits Partial Involvement in Thyroxin-induced Cardiomyocyte Hypertrophy and Its Inhibition Is Not Sufficient to Improve Cardiac Dysfunction or Contractile Abnormalities in Mouse Papillary Muscles

: Development of cardiac hypertrophy after thyroxin (T4) treatment is well recognized. Recently, we observed that T4-induced cardiac hypertrophy is associated with increased cardiac Rac1 expression and activity. Whether this Rac1 increase has a role in inducing this cardiac phenotype is, however, still unknown. Here, we showed that T4 treatment (500 µg/kg/d) for 2 weeks resulted in increased myocardial Rac1 activity with subsequent hypertension, cardiac hypertrophy, and left ventricular systolic dysfunction in vivo. Isolated right ventricular papillary muscles of T4-treated mice maintained their peak isometric active developed tension but exhibited significant decreases in their corresponding time to peak and in relaxation times. Positive inotropic responses to increasing pacing rate and β-adrenergic stimulation were also depressed in these muscles. Pravastatin (10 mg/kg/d), a Rac1 inhibitor, significantly decreased myocardial Rac1 activity, hypertension, and cardiomyocyte size in T4-treated mice but could not attenuate gross heart weight or functional cardiac changes in these mice. Our data showed that T4 could activate different signaling pathways with distinct cardiovascular outcomes. We also provide the first mechanistic evidence for the partial involvement of Rac1 activation in T4-induced cardiomyocyte hypertrophy and reveal a putative role for Rac1 in the development of T4-induced hypertension.

Role of Rac1 in Thyroxin-Induced Cardiovascular Abnormalities

Development of cardiac hypertrophy (CH) after thyroxin (T4) treatment is well established. Many signaling pathways have been implicated in this phenomenon such as PI3K, PKB/Akt, or the rennin-angiotensin system. Recently, we observed that T4-induced CH is associated with increased cardiac Rac1 expression and activity. Whether these increases have a role in inducing this cardiac outcome still unknown. Here, we showed that T4 treatment (500 μg/kg/day) for two weeks resulted in CH and hypertension in mice. Left ventricular systolic function is also decreased in these mice compared to WT. Under near physiological conditions, right ventricular papillary muscles of T4-treated mice maintained their peak isometric active developed tension, but exhibited significant decreases in their corresponding time to peak, 50% relaxation, and 90% relaxation times. Positive inotropic responses to increasing heart rate (frequency) and β-adrenergic stimulation were markedly depressed in these muscles compared to WT. Rac1 inhibitor, pravastatin (10 mg/kg/day) significantly decreased the T4-induced hypertension but not the CH or any of the T4-induced contractile changes in cardiac muscles. In conclusion, T4 induces different signaling pathways with different cardiac outcomes. Rac1 seems to play a role in T4-induced hypertension with a minor involvement in T4-induced CH. Contractile abnormalities of cardiac muscles after T4 treatment are apparently dependent on CH but not hemodynamic changes (elevated blood pressure). Early treatment of T4-induced CH could represent a valuable therapeutic strategy to prevent progression to heart failure in hyperthyroid patients.

Vascular Remodeling–Associated Hypertension Leads to Left Ventricular Hypertrophy and Contractile Dysfunction in Profilin-1 Transgenic Mice

Hypertension is a major health problem and a main risk factor for cardiovascular diseases. We have shown that overexpression of profilin-1 in blood vessels of transgenic mice generates mechanical tone and led to vascular remodeling/hypertension. However, little is known whether cardiac contractile performance in these mice is compromised. We investigated the in vivo contractile function and in vitro contractile performance using isolated papillary muscles from both right ventricle and left ventricle of profilin-1 mice at older age. Our results showed mild left ventricular hypertrophy and moderate systolic dysfunction in profilin-1 mice as evident by increased heart/body weight ratio and echocardiography analysis. Under near physiological conditions, right ventricle papillary muscles of profilin-1 mice maintained their peak isometric active developed tension, and the rate of force development over the entire frequency range of 4-14 Hz. Positive inotropic responses to increasing Ca and β-adrenergic stimulation were also maintained. Conversely, left ventricular papillary muscles of profilin-1 mice exhibited depressed peak isometric, peak isometric active developed tension and rate of force development, and depressed positive inotropic responses to increasing Ca and β-adrenergic stimulation. We here provide functional evidence that a significant contractile dysfunction in profilin-1 mice exists. Targeting vascular profilin-1 signaling could represent a promising therapeutic approach in hypertensive patients.

Effect of New Zealand blueberry consumption on recovery from eccentric exercise-induced muscle damage

BackgroundExercise-induced muscle damage (EIMD) is accompanied by localized oxidative stress / inflammation which, in the short-term at least, is associated with impaired muscular performance. Dietary antioxidants have been shown to reduce excessive oxidative stress; however, their effectiveness in facilitating recovery following EIMD is not clear. Blueberries demonstrate antioxidant and anti-inflammatory properties. In this study we examine the effect of New Zealand blueberries on EIMD after strenuous eccentric exercise.MethodsIn a randomized cross-over design, 10 females consumed a blueberry smoothie or placebo of a similar antioxidant capacity 5 and 10 hours prior to and then immediately, 12 and 36 hours after EIMD induced by 300 strenuous eccentric contractions of the quadriceps. Absolute peak and average peak torque across the knee, during concentric, isometric, and eccentric actions were measured. Blood biomarkers of oxidative stress, antioxidant capacity, and inflammation were assessed at 12, 36 and 60 hours post exercise. Data were analyzed using a two-way ANOVA.ResultsA significant (p < 0.001) decrease in isometric, concentric and eccentric torque was observed 12 hours following exercise in both treatment groups. During the 60 hour recovery period, a significant (p = 0.047) interaction effect was seen for peak isometric tension suggesting a faster rate of recovery in the blueberry intervention group. A similar trend was observed for concentric and eccentric strength. An increase in oxidative stress and inflammatory biomarkers was also observed in both treatment groups following EIMD. Although a faster rate of decrease in oxidative stress was observed in the blueberry group, it was not significant (p < 0.05) until 36 hours post-exercise and interestingly coincided with a gradual increase in plasma antioxidant capacity, whereas biomarkers for inflammation were still elevated after 60 hours recovery.ConclusionsThis study demonstrates that the ingestion of a blueberry smoothie prior to and after EIMD accelerates recovery of muscle peak isometric strength. This effect, although independent of the beverage’s inherent antioxidant capacity, appears to involve an up-regulation of adaptive processes, i.e. endogenous antioxidant processes, activated by the combined actions of the eccentric exercise and blueberry consumption. These findings may benefit the sporting community who should consider dietary interventions that specifically target health and performance adaptation.

The effects of vibration therapy on muscle force loss following eccentrically induced muscle damage

The purpose of this study was to investigate the effects of acute vibration therapy (VT) on performance recovery after a bout of strenuous eccentric exercise. Eight healthy males completed 300 maximal eccentric contractions of the quadriceps of one leg on an isokinetic dynamometer. Immediately after exercise and 12 and 24 h post-exercise, the subjects underwent either VT or a control treatment of no VT. Five sets of 1 min VT was performed at 26 Hz, with 6 mm peak-to-peak displacement, on a commercially available vibration machine. At least 2 weeks after the initial trial, the subjects completed the second trial using the contralateral leg and other treatment. Peak and average peak isometric tension and isokinetic concentric and eccentric torque were measured prior to exercise and 24 and 48 h post-exercise. Treatment with VT resulted in significantly (all P < 0.05) greater decrements in peak (-38%) and average peak eccentric (-39%) torque 24 h after eccentric exercise as compared to a control treatment (-24 and -29%, respectively). These results suggest that the use of 26 Hz VT in the first 24 h after damaging exercise may be detrimental to the magnitude of force loss and/or recovery over this period.

Lengthening-contractions in isolated myocardium impact force development and worsen cardiac contractile function in the mdx mouse model of muscular dystrophy

Lengthening-contractions exert eccentric stress on myofibers in normal myocardium. In congestive heart failure caused by a variety of diseases, the impact of lengthening-contractions of myocardium likely becomes more prevalent and severe. The present study introduces a method to investigate the role of stretching imposed by repetitive lengthening-contractions in myocardium under near-physiological conditions. By exerting various stretch-release ramps while the muscle is contracting, consecutive lengthening-contractions and their potential detrimental effect on cardiac function can be studied. We tested our model and hypothesis in age-matched (young and adult) mdx and wild-type mouse right ventricular trabeculae. These linear and ultrathin muscles possess all major cardiac cell types, and their contractile behavior very closely mimics that of the whole myocardium. In the first group of experiments, 10 lengthening-contractions at various magnitudes of stretch were performed in trabeculae from 10-wk-old mdx and wild-type mice. In the second group, 100 lengthening-contractions at various magnitudes were conducted in trabeculae from 10- and 20-wk-old mice. The peak isometric active developed tension (F(dev), in mN/mm(2)) and kinetic parameters time to peak tension (TTP, in ms) and time from peak tension to half-relaxation (RT50, in ms) were measured. Our results indicate lengthening-contractions significantly impact contractile behavior, and that dystrophin-deficient myocardium in mdx mice is significantly more susceptible to these damaging lengthening-contractions. The results indicate that lengthening-contractions in intact myocardium can be used in vitro to study this emerging contributor to cardiomyopathy.

Enhancement of shortening velocity, power, and acto‐myosin crossbridge (CB) kinetics following long‐term treatment with propionyl‐L‐carnitine, coenzyme Q10, and omega‐3 fatty acids in BIO TO‐2 cardiomyopathic Syrian hamsters papillary muscle

Impaired functions of myocardial muscle cells in human and animals, is a primary defect associated with idiopathic dilated cardiomyopathy (DCM). The pathophysiological mechanisms implicated in the DCM are yet to be clarified and an effective therapy is still not available. The BIO TO-2 cardiomyopathic Syrian Hamsters (CMSHs) represent an animal model of idiopathic DCM. The aim of this study was to investigate the effect of long-term treatment (2 months) with propionyl-L-carnitine (PLC), coenzyme Q(10), omega-3 fatty acids and a combination of these three agents (formulation HS12607) on mechanical properties and acto-myosin crossbridges (CBs) kinetics of left ventricular (LV) papillary muscle from control and treated 10 month old BIO TO-2 CMSHs. Isometric and isotonic contractile properties of isolated papillary muscle from control and treated CMSHs were investigated, and acto-myosin CB number, force and kinetics were calculated using Huxley's equations. Mechanical parameter values were higher in treated than in control hamsters, particularly when substances were administered together in a coformulation (HS12607). Compared to control, HS12607-treated papillary muscles showed a significant increase of maximum peak isometric tension (P(o)) (30.06 +/- 4.91 vs. 19.74 +/- 5.00 mN/mm(2)), maximum extent of muscle shortening (0.13 +/- 0.03 vs. 0.07 +/- 0.02 L/L(max)), maximum unloaded shortening velocity (1.18 +/- 0.24 vs. 0.53 +/- 0.13 L/L(max) s(-1)) and maximum peak of power output (5.52 +/- 1.61 vs. 1.58 +/- 0.83). The curvature of the hyperbolic force-velocity relationships did not differ between control and treated hamsters. When compared to controls, acto-myosin CB number increased in treated hamsters [(6.67 +/- 1.91) 10(10)/mm(2) vs. (3.55 +/- 2.08) 10(10)/mm(2)], whereas the unitary force of single CB was similar in control and treated animals. The peak value of the rate constant for CB attachment (f(1)) and detachment (g(2)) was higher in treated animals when compared to control. (93.87 +/- 25.82 vs.47.28 +/- 10.88 s(-1) and 214.40 +/- 44.64 vs. 95.56 +/- 23.49 s(-1), respectively). In conclusion, the present study illustrates that supplementation with PLC, CoQ(10) and omega-3 fatty acids improved motor parameters, energetic, and CB kinetics of BIO TO-2 CMSH papillary muscle indicating that these naturally occurring substances may be a valid adjuvant to conventional therapy in DCM.

Contraction-Mediated Damage in mdx Mice Trabeculae: A Model for Cardiomyopathy in Duchene Muscular Dystrophy

Duchene muscular dystrophy (DMD) is an inherited and progressive disease of striated muscle deterioration. Studies on skeletal muscle using an eccentric contraction model have provided great insight of the contraction-mediated damage in skeletal muscle in DMD. Because of different contraction mechanics in the cardiac vs. skeletal muscle, the protocols used to gain understanding in skeletal muscle pathology cannot be readily applied to the myocardium. To investigate contraction-mediated damage in dystrophin-deficient myocardium under physiological conditions, we developed an in vitro model of myocardial mechanics-induced injury. We employed computer-programmed protocols to trigger consecutive lengthening ramps during the twitch contraction at 4 Hz in age matched (young and adult) mdx and wild type mice right ventricular trabeculae. These ultra-thin muscles possess all major cardiac cell types and their contractile behavior very closely mimics that of the whole heart. In the first group of experiments, 10 lengthening contractions of various (1-10%) magnitude of stretch were performed in trabeculae from 10 week old mdx and wild type mice. In the second group, 100 lengthening contractions at each magnitude were conducted in trabeculae from 20 weeks old mice. The peak isometric active developed tension (Fdev, in mN/mm2), diastolic tension (Fdia), and force kinetics were measured throughout the protocol, and the rate of decline of these parameters can be taken as a relative measurement of how susceptible the myocardium is to lengthening-induced dysfunction. Our results indicate dystrophin deficient myocardium in older mdx mice is more sensitive to severe mechanical stress compared to age-matched wild type controls. This suggests that lengthening contraction in myocardium is an appropriate model to study contraction-mediated damage in DMD associated cardiomyopathy.

Temperature and Doublet Potentiation: Effects of Varied Interspike Interval

The addition of two closely spaced pulses (doublets) at the beginning of alow‐frequency train of stimuli has been shown to increase peak isometric tension (PT) and tension‐time integral (TTI). This study examined the effects of cooling on potentiation associated with paired pulses having varied (10–100 ms) interspike intervals (ISIs). Sartorii muscles (60–70 mg) from male R. pipiens were dissected free and mounted vertically in water‐jacketed chambers containing oxygenated (100%) Ringer solution (pH 7.2). Muscles were exposed serially to single (SES) and paired (i.e., doublet; DES) electrical stimulation. DES was adjusted to produce ISIs ranging from 10–100 ms. PT (g/g) was measured via field stimulation with supramaximal square wave pulses (1 ms). At 20°C, PT in response to DES (ISI = 100 ms; PTD) was elevated when compared to SES (PTS): 105.7 ± 21.5 v. 79.5 ± 10.0, respectively. Decreasing ISI produced further increases in PTD, with maximum PTD occurring at an ISI of 10 ms: 178.0 ± 34.0 v. 79.5 ± 10.0, respectively. At 10°C, PTS at was increased when compared to 20°C: 120.7 ± 8.1 (10°C) v. 79.5 ± 10.0, respectively. Furthermore, PTD (10°C; ISI = 100 ms) was also elevated when compared to SES (10°C); 196.7 ± 22.5 v. 120.7 ± 8.1, respectively. Decreasing ISI produced additional increases in PTD. However, maximum PTD was developed when paired pulses were actually than 10 ms (i.e., ISI = 40 ms). ISIs &lt; 40 ms failed to produce further increases in PTD. Calculated values for TTI (g·s) were similarly affected. These results suggest that: 1) the potentiating effect of paired stimulation is temperature‐sensitive, and 2) the efficacy of paired stimulation in vivo, as a potential neural control strategy to augment force production, may be mediated by environmental factors.

Is Phospholamban or Troponin I the “Prima Donna” in β-Adrenergic Induced Lusitropy?

See related articles, pages 377–386 In normal myocardium, acute β-adrenergic stimulation augments both systolic and diastolic performance via protein kinase A (PKA)–mediated phosphorylation of key proteins governing Ca2+ handling and the contractile machinery. Twenty-five years ago Kranias and Solaro identified troponin I (TnI) and phospholamban (PLN) as the 2 major cardiac proteins which were nearly simultaneously phosphorylated by β-adrenergic stimulation of the beating heart in synchrony with the agonist effect of augmenting contractility (inotropy) and rate of relaxation (lusitropy).1 Numerous subsequent studies have mechanistically examined the role of these proteins in inotropy and lusitropy. It is well established that enhanced Ca2+ availability during systole is the major, though perhaps not the only, driver of enhanced inotropy with β- adrenergic stimulation.2–4 The effect on Ca2+ dynamics is primarily mediated by phosphorylation of PLN, though increased ionic current through the L-type calcium channel contributes to Ca2+ loading. When PLN is phosphorylated by PKA, the “brake” imposed by PLN on sarcoplasmic reticulum (SR) Ca2+ ATPase is relieved, resulting in an increase in the activity of the latter that leads to a faster sequestration of Ca2+ into the SR, enhancing cardiac relaxation and re-loading the SR with Ca2+ to increase Ca2+ release in subsequent beats. Yet, PLN phosphorylation by PKA is not the sole mechanism implicated in enhancing relaxation. In particular, phosphorylation of TnI by PKA has long been proposed to have a role in diastole because it desensitizes the myofilament to Ca2+, increases the off rate of Ca …

Utrophin deficiency worsens cardiac contractile dysfunction present in dystrophin-deficient mdx mice

The loss of dystrophin in patients with Duchenne muscular dystrophy (DMD) causes devastating skeletal muscle degeneration and cardiomyopathy. Dystrophin-deficient (mdx) mice have a much milder phenotype, whereas double knockout (DKO) mice lacking both dystrophin and its homolog, utrophin, exhibit the clinical signs observed in DMD patients. We have previously shown that DKO and mdx mice have similar severities of histological features of cardiomyopathy, but no contractile functional measurements of DKO heart have ever been carried out. To investigate whether DKO mice display cardiac dysfunction at the tissue level, contractile response of the myocardium was tested in small, unbranched, ultrathin, right ventricular muscles. Under near physiological conditions, peak isometric active developed tension (F(dev), in mN/mm2) at a stimulation frequency of 4 Hz was depressed in DKO mice (15.3 +/- 3.7, n = 8) compared with mdx mice (24.2 +/- 5.4, n = 7), which in turn were depressed compared with wild-type (WT) control mice (33.2 +/- 4.5, n = 7). This reduced Fdev was also observed at frequencies within the murine physiological range; at 12 Hz, Fdev was (in mN/mm2) 11.4 +/- 1.8 in DKO, 14.5 +/- 4.2 in mdx, and 28.8 +/- 5.4 in WT mice. The depression of Fdev was observed over the entire frequency range of 4-14 Hz and was significant between DKO versus mdx mice, as well as between DKO or mdx mice versus WT mice. Under beta-adrenergic stimulation (1 micromol/l isoproterenol), Fdev in DKO preparations was only (in mN/mm2) 14.7 +/- 5.1 compared with 30.9 +/- 8.9 in mdx and 41.0 +/- 4.9 in WT mice. These data show that cardiac contractile dysfunction of mdx mice is generally worsened in mice also lacking utrophin.

Age-Related Variability in Single Muscle Fiber Contractile Properties

1397 The biological process of aging has been associated with an increased variability in physiological functions. PURPOSE: To assess the effect of age on variability of single muscle fiber isometric contractile properties in a large population of healthy adults. METHODS: Percutaneous biopsies were obtained from the vastus lateralis of 73 subjects classified by age and gender into 4 groups: young males (YM: n = 8, mean age 37 yrs), older males (OM: n = 20, mean age 70), young females (YF: n = 10, mean age 29), and older females (OF: n = 35, mean age 60). Cross sectional area (CSA), peak isometric tension (Po), and maximum unloaded shortening velocity (Vo) were measured in 1671 chemically skinned single muscle fibers. Vo was determined using the slack test. Myosin heavy chain isoform expression was identified using SDSPAGE. Descriptive statistics were performed by fiber type, age, and gender. Standard deviation was used as a measure of variability for each parameter. RESULTS: In older adults, variability increases for CSA, decreases for Po, and shows no consistent trend for Vo.Table: No Caption available.n = number of single fibers CONCLUSION: This data set characterizes the variability in single muscle fiber contractile properties of a large population of healthy individuals. With age, variation in single muscle fiber size increases, but there is not an accompanying increase in variability of contractile properties.

Mechanical Properties of Tracheal Smooth Muscle Are Impaired in the Rabbit With Experimental Cardiac Pressure Overload

STUDY OBJECTIVES/DESIGN: Impaired function of striated and arterial smooth muscle is known to occur in humans and animals with various forms of cardiac diseases, but limited information is available on the mechanical behavior of airway smooth muscle. We tested the hypothesis that the baseline mechanical properties of tracheal smooth muscle (TSM) were impaired at an early stage of cardiac overload. We used a model of cardiac hypertrophy induced by surgical abdominal aortic stenosis (AS) in adult rabbits. Twelve animals with AS and 8 sham-operated control rabbits were studied 12 weeks after surgery. In rabbits with AS, the heart weight/body weight ratio was higher than in control rabbits (2.36 +/- 0.43 g/kg vs 1.98 +/- 0.20 g/kg, p < 0.05) [mean +/- SD], attesting to moderate cardiac hypertrophy. No clinical signs of congestive heart failure were observed. Isolated TSM strips were electrically stimulated at 37 degrees C, 2.5 mM [Ca(2+)](0), against 8 to 10 load levels, from zero load to full isometry. Force-velocity relationship was elicited using the conventional afterloaded isotonic method. Peak isometric tension was lower in rabbits with AS than in control rabbits (25 +/- 11 mN/mm(2) vs 34 +/- 14 mN/mm(2), p < 0.05), whereas maximum unloaded shortening velocity, maximum extent of muscle shortening, and relaxation parameters did not differ between groups. The curvature of the force-velocity relationship (which reflects the myothermal economy of force generation) and peak mechanical efficiency were lower in rabbits with AS than in control rabbits. These results indicate that the contraction of isolated rabbit TSM was less powerful and less economical in cardiac hypertrophy, attesting to early impairment of the mechanical properties of TSM during cardiac overload.

Rises in whole muscle passive tension of mammalian muscle after eccentric contractions at different lengths.

This is a report of experiments carried out on the medial gastrocnemius muscle of the anesthetized cat, investigating the effects of eccentric contractions carried out at different muscle lengths on the passive and active length-tension relationships. In one series of experiments, the motor supply to the muscle was divided into three approximately equal parts; in the other, whole muscles were used. Fifty eccentric contractions were carried out over different regions of the active length-tension curve for each partial or whole muscle. Active and passive length-tension curves were measured before and after the eccentric contractions. When eccentric contractions were carried out at longer lengths, there was a larger shift of the optimum length for active tension in the direction of longer muscle lengths and a larger fall in peak isometric tension. Passive tension was higher immediately after the eccentric contractions, and if the muscle was left undisturbed for 40 min, it increased further to higher values, particularly after contractions at longer lengths. A series of 20 passive stretches of the same speed and amplitude and covering the same length range as the active stretches, reduced the passive tension which redeveloped over a subsequent 40-min period. It is hypothesized that there are two factors influencing the level of passive tension in a muscle after a series of eccentric contractions. One is injury contractures in damaged muscle fibers tending to raise passive tension; the other is the presence of disrupted sarcomeres in series with still-functioning sarcomeres tending to reduce it.

Aging does not attenuate plantaris muscle hypertrophy in male Fischer 344 rats.

The present study examined the effect of extreme old age on the plasticity of the rat plantaris muscle in response to an increase in mechanical load. Male Fischer 344 rats, aged 7 months (adult) and 25 months (old) underwent bilateral surgical ablation of the gastrocnemius muscle to functionally overload (OV) the fast-twitch plantaris muscle for 8 wk At 27 months of age, plantaris wet weight and cross-sectional area (CSA) were unaffected by age, but aging decreased peak isometric tension (Po) 27% (P < 0.05). Plantaris muscle myosin heavy chain composition indicated a loss of faster myosin heavy chains (MHC) isoforms with concomitant increases in slower MHC in old rats (P < 0.05). In adult rats, OV increased muscle CSA and Po 72% and 83%, respectively (P < 0.05). Similarly, OV increased CSA and Po 69% and 73%, respectively, in old rats (P < 0.05). Average fiber CSA increased 57% and 68% in adult-OV and old-OV rats, respectively (P < 0.05). Collectively, our data indicate that plantaris muscle mass and plasticity in response to increased mechanical load are well conserved in very aged male Fischer 344 rats.

EFFECT OF PROGRESSIVE RESISTANCE TRAINING ON SINGLE MYOFIBER CALCIUM SENSITIVITY IN OLDER WOMEN

The purpose of this investigation was to determine the effects of a 12-week progressive resistance-training program (PRT) on single myofiber calcium sensitivity in six older women (73 ± 2 yr.). Muscle biopsies of the vastus lateralis were obtained pre-and-post PRT. Single muscle fibers were dissected and mounted between a lever arm and force transducer in an experimental chamber. The experimental sequence for each fiber was the determination of maximal isometric tension (Po) at pCa 4.5 (pCa = −log[Ca2+]), and then subsequent submaximal activations of the fiber at nine Ca2+ concentrations (pCa 6.8 to 4.7). MHC I and IIa fiber diameter increased 16% (p < 0.05) and 2% pre-to-post PRT, respectively. Peak isometric tension in MHC I and IIa fibers increased 34% (p < 0.05) and 18% as a result of the training. The mean MHC I Ca2+ activation threshold increased from 6.83 ± 0.02 to 6.91 ± 0.01 (p < 0.05) as did the mean half-maximal activation 5.51 ± 0.02 to 5.71 ± 0.03 (p < 0.05) with PRT. The slope of the Hill plot above (n1) half-maximal activation for MHC I did not change significantly with the PRT (1.80 ± 0.04 to 1.86 ± 0.08). However, the slope of the Hill plot below (n2) half-maximal activation for MHC I demonstrated an increase (p < 0.05) with training (1.70 ± 0.11 to 2.43 ± 0.09). There were no differences with MHC IIa fibers with PRT for any of the Ca2+ variables measured. In conclusion, the results of this investigation indicate that myofibril ca2+ sensitivity and activation properties are altered in MHC I, but not MHC IIa fibers with PRT in older women. The alterations in the MHC I Ca2+ properties appear to have a significant effect on the mechanisms involved with skeletal muscle adaptability in older women following PRT. Supported by NIH AG154876

Lack of skeletal muscle hypertrophy in very aged male Fischer 344 x Brown Norway rats.

To examine the effect of extreme old age on muscle plasticity, 6- (adult) and 36-mo-old (old) male Fischer 344 x Brown Norway hybrid rats underwent bilateral surgical ablation of the gastrocnemius muscle to functionally overload (OV) the fast-twitch plantaris muscle for 8 wk. Plantaris muscle wet weight, muscle cross-sectional area (CSA), and average fiber CSA decreased by 44, 42, and 40%, respectively, in old compared with adult rats, and peak isometric tetanic tension decreased by 83%. Compared with muscles in age-matched controls, plantaris muscle mass increased by 53% and type I, IIA, and IIX/IIB CSA increased by 91, 76, and 103%, respectively, in adult-OV rats, but neither wet mass nor fiber CSA increased in old-OV rats. OV decreased type I, IIA, and IIX/IIB mean fiber CSA by 31, 35, and 30%, respectively, in old-OV rats. Collectively, our data indicate that in extreme old age the plantaris muscle undergoes significant loss of mass, fiber CSA, and contractile function, as well as its capacity to undergo hypertrophy in response to a chronic increase in mechanical load.