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Loaded shortening and power output in cardiac myocytes are dependent on myosin heavy chain isoform expression.

The purpose of this study was to examine the role of myosin heavy chain (MHC) in determining loaded shortening velocities and power output in cardiac myocytes. Cardiac myocytes were obtained from euthyroid rats that expressed alpha-MHC or from thyroidectomized rats that expressed beta-MHC. Skinned myocytes were attached to a force transducer and a position motor, and isotonic shortening velocities were measured at several loads during steady-state maximal Ca(2+) activation (P(pCa4.5)). MHC expression was determined after mechanical measurements using SDS-PAGE. Both alpha-MHC and beta-MHC myocytes generated similar maximal Ca(2+)-activated force, but alpha-MHC myocytes shortened faster at all loads and generated approximately 170% greater peak normalized power output. Additionally, the curvature of force-velocity relationships was less, and therefore the relative load optimal for power output (F(opt)) was greater in alpha-MHC myocytes. F(opt) was 0.31 +/- 0.03 P(pCa4.5) and 0.20 +/- 0.06 P(pCa4.5) for alpha-MHC and beta-MHC myocytes, respectively. These results indicate that MHC expression is a primary determinant of the shape of force-velocity relationships, velocity of loaded shortening, and overall power output-generating capacity of individual cardiac myocytes.

Animals↗

Influence of crossbridge compliance on the force-velocity relation of muscle.

It is shown that muscle models which describe force generation as being dependent on the extension of the individual crossbridges produce a force-velocity relation of the form: Vf= Visotonic--1/KHS dP/dt. The derivation of this equation is independent of the details of activation and the kinetics of the crossbridges. The velocity, Vf, represents the relative filament velocity, and Visontonic is the relative filament velocity which would maintain a constant muscle force. P. The quantity KHS is the net stiffness of all the force-generating crossbridges in one-half a sarcomere. Experimental methods for determining KHS are suggested . To study the force-velocity relation, computer simulations based on A. F.Huxley's 1957 kinetic model were conducted for isometric and isotonic twitch contractions. The relative filament velocity is found to depend on the contraction mode, exhibiting a sudden increase in an isometric-to-isontonic changeover and a decrease in the reverse process.

Biomechanical Phenomena↗

Sex differences in postexercise esophageal and muscle tissue temperature response.

Factors associated with blood pressure regulation during recovery from exercise dramatically influence core temperature regulation. However, it is unknown whether sex-related differences in postexercise hemodynamics affect core and muscle temperature response. Sixteen participants (8 males, 8 females) completed an incremental isotonic test on a Kin-Com isokinetic apparatus to determine their activity-specific peak oxygen consumption during bilateral knee extensions (Vo(2)(sp)). On a separate day, participants performed 15 min of isolated bilateral knee extensions at a moderate (60% Vo(2)(sp)) exercise intensity followed by a 90-min recovery. Esophageal temperature (T(es)), mean arterial pressure (MAP), muscle temperature at four depths in the active vastus medialis (T(VM)) and three depths in the inactive triceps brachii (T(TB)) were measured concurrently with sweat rate and cutaneous vascular conductance (CVC). Relative to the preexercise resting T(es) of 36.7 degrees C (SD 0.1), between 10 and 50-min of recovery T(es) was 0.19 degrees C (SD 0.02) higher for females than males (P = 0.037). All measurements of T(VM) (0.036 > P > 0.014) and T(TB) (0.048 > P > 0.008) were higher for females during the initial 30 min of recovery by between 0.46 degrees C and 0.64 degrees C for T(VM) and by between 0.53 degrees C and 0.70 degrees C for T(TB). In parallel, females showed a 5 to 7 mmHg greater reduction in MAP during recovery relative to males (P = 0.002) and a significantly lower CVC (P = 0.020) and sweat rate (P = 0.034). Therefore, it is concluded that females demonstrate a greater and more prolonged elevation in postexercise esophageal temperature and active and inactive muscle temperatures, which is paralleled by a greater postexercise hypotensive response.

Adult↗

Stretch-mediated visceral smooth muscle growth in vitro.

An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5-fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors.

Aging↗

Contractile properties of rat, rhesus monkey, and human type I muscle fibers.

It is well known that skeletal muscle intrinsic maximal shortening velocity is inversely related to species body mass. However, there is uncertainty regarding the relationship between the contractile properties of muscle fibers obtained from commonly studied laboratory animals and those obtained from humans. In this study we determined the contractile properties of single chemically skinned fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius muscle samples under identical experimental conditions. All fibers used for analysis expressed type I myosin heavy chain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I fibers from each muscle indicated that there was little change in peak tension (force/fiber cross-sectional area) across species. In contrast, both soleus and gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y-intercept of the force-velocity relationship (Vmax), peak power per unit fiber length, and peak power normalized for fiber length and cross-sectional area were all inversely related to species body mass. The present allometric coefficients for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published values for soleus fibers obtained from common laboratory and domesticated mammals. Taken together, these observations suggest that the Vo of slow fibers from quadrupeds and humans scale similarly and can be described by the same quantitative relationships. These findings have implications in the design and interpretation of experiments, especially those that use small laboratory mammals as a model of human muscle function.

Animals↗

Blood flow distribution in dog gastrocnemius muscle at rest and during stimulation.

The distribution of blood flow within the isolated perfused dog gastrocnemius muscle (weight 100-240 g) was studied by intra-arterial injection of radioactively labeled microspheres (diameter 15 micron) at rest and during supramaximal stimulation to rhythmic isotonic tetanic contractions of varied frequency against varied loads. After the experiment the muscle was cut into 180-250 pieces of approximately 0.75 g each, and the blood flow to each muscle piece was determined from its radioactivity. The inhomogeneity of blood flow was represented as the frequency distribution of the ratios of regional specific blood flow, i.e., blood flow per unit tissue weight of the piece, QR, to the overall specific blood flow of the muscle, Q. The QR/Q values for the individual pieces of a muscle were found to vary widely both at rest and during stimulation. With rising work load the frequency distribution had a tendency to broaden and flatten, indicating increasing perfusion inhomogeneity. On the average of the experiments, there was no significant difference in specific blood flow between the three anatomic components of the gastrocnemius (lateral and medial heads of gastrocnemius and flexor digitorum superficialis) nor between the superficial and deep portions within these anatomic components, only the distal third of the muscle was relatively less perfused compared with the proximal two-thirds. The considerable inhomogeneity of blood flow as revealed by microsphere embolization and by other methods is expected to exert important limiting effects on local O2 supply, particularly during exercise. Its neglect would lead to serious errors in the analysis of O2 supply to muscle tissue.

Animals↗

Effects of adrenergic agonists and antagonists on muscle O2 uptake and lactate metabolism.

To investigate adrenergic receptor-mediated responses in dog gastrocnemius-plantaris muscle, several catecholamine agonists, isoproterenol, epinephrine, norepinephrine, and phenylephrine, and two antagonists, propranolol and phenoxybenzamine, were given during repetitive, isotonic, tetanic contractions. The response variables that were measured were muscle blood flow, shortening during constant load contractions, and arterial and venous O2 and lactate concentrations. The calculated variables were O2 uptake (VO2), net lactic acid output (L), and power output. In the control experiments, the contractions increased VO2 to approximately 50 times rest by 2 min. Thereafter, shortening, work, and VO2 declined together by 17% at 30 min, indicating muscle fatigue. L increased rapidly to nearly 0.8 mumol X g-1 X min-1 by 2 min, declined to 0.3-0.4 mumol X g-1 X min-1 by 7 min, and was like rest at 15, 22.5, and 30 min. The arterial lactate concentration rose steadily from rest to 30 min of contractions. Epinephrine infusion stopped the decline of VO2 during the contractions, but this effect was not observed with the other agonists. Propranolol decreased VO2 compared with controls at 22.5 and 30 min of contractions. Phenoxybenzamine decreased VO2 compared with controls at all times during contraction, and the decline with time was present. Coinfusion of epinephrine with propranolol reduced the decline in VO2 observed with propranolol alone. Both epinephrine and isoproterenol increased L compared with controls. This epinephrine response was antagonized by propranolol but enhanced by phenoxybenzamine. Both isoproterenol and epinephrine infusions increased arterial lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Agonists↗

Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training.

The purpose was to test the hypothesis that twice daily, short-term, variable intensity isotonic and intermittent high-intensity isokinetic leg exercise would maintain peak O2 uptake (VO2) and muscular strength and endurance, respectively, at or near ambulatory control levels during 30 days of -6 degrees head-down bed rest (BR) deconditioning. Nineteen men (aged 32-42 yr) were divided into no exercise control (peak VO2 once/wk, n = 5), isokinetic (Lido ergometer, n = 7), and isotonic (Quinton ergometer, n = 7) groups. Exercise training was conducted in the supine position for two 30-min periods/day for 5 days/wk. Isotonic training was at 60-90% of peak VO2, and isokinetic training (knee flexion-extension) was at 100 degrees/s. Mean (+/- SE) changes (P less than 0.05) in peak VO2 (ml.m-1.kg-1) from ambulatory control to BR day 28 were 44 +/- 4 to 36 +/- 3, -18.2% (3.27-2.60 l/m) for no exercise, 39 +/- 4 to 40 +/- 3, +2.6% (3.13-3.14 l/min) for isotonic, and 44 +/- 3 to 40 +/- 2, -9.1% (3.24-2.90 l/min) for isokinetic. There were no significant changes in any groups in leg peak torque (right knee flexion or extension), leg mean total work, arm total peak torque, or arm mean total work. Mean energy costs for the isotonic and isokinetic exercise training were 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1) and 214 kcal/h (8.9 +/- 0.5 ml.m-1.kg-1), respectively. Thus near-peak, variable intensity, isotonic leg exercise maintains peak VO2 during 30 days of BR, while this peak, intermittent, isokinetic leg exercise protocol does not.

Adult↗

Myofibrillar or mitochondrial creatine kinase deficiency alone does not impair mouse diaphragm isotonic function.

Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. The diaphragm (Dia) expresses both M-CK and ScCKmit in abundance. We compared the power and work output of 1) control CK-sufficient (Ctl), 2) M-CK-deficient [M-CK(-/-)], 3) ScCKmit-deficient [ScCKmit(-/-)], and 4) combined M-CK/ScCKmit-deficient null mutant [CK(-/-)] Dia during repetitive isotonic activations to determine the effect of CK phenotype on Dia function. Maximum power was obtained at approximately 0.4 tetanic force in all groups. M-CK(-/-) and ScCKmit(-/-) Dia were able to sustain power and work output at Ctl levels during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load), and the duration of sustained Dia shortening was 67 +/- 4 s in M-CK(-/-), 60 +/- 4 s in ScCKmit(-/-), and 62 +/- 5 s in Ctl Dia. In contrast, CK(-/-) Dia power and work declined acutely and failed to sustain shortening altogether by 40 +/- 6 s. We conclude that Dia power and work output are not absolutely dependent on the presence of either M-CK or ScCKmit, whereas the complete absence of CK acutely impairs Dia shortening capacity during repetitive activation.

Animals↗

Effect of resistance training on single muscle fiber contractile function in older men.

The purpose of this study was to examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older men (n = 7; age = 74 +/- 2 yr and weight = 75 +/- 5 kg). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy samples were obtained from the vastus lateralis before and after PRT (pre- and post-PRT, respectively). For analysis, chemically skinned single muscle fibers were studied at 15 degrees C for peak tension [the maximal isometric force (P(o))], unloaded shortening velocity (V(o)), and force-velocity parameters. In this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the minimal number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 +/- 1 to 100 +/- 1 microm) and 13% (86 +/- 1 to 97 +/- 2 microm) in MHC I and IIa fibers, respectively (P < 0.05). P(o) was higher (P < 0.05) in MHC I (0.58 +/- 0.02 to 0.90 +/- 0.02 mN) and IIa (0.68 +/- 0.02 to 0.85 +/- 0.03 mN) fibers. Muscle fiber V(o) was elevated 75% (MHC I) and 45% (MHC IIa) after PRT (P < 0.05). MHC I and IIa fiber power increased (P < 0.05) from 7.7 +/- 0.5 to 17.6 +/- 0.9 microN. fiber lengths. s(-1) and from 25.5 to 41.1 microN. fiber lengths. s(-1), respectively. These data indicate that PRT in elderly men increases muscle cell size, strength, contractile velocity, and power in both slow- and fast-twitch muscle fibers. However, it appears that these changes are more pronounced in the MHC I muscle fibers.

Aged↗

Effects of volatile anesthetics on stiffness of mammalian ventricular muscle.

To assess the effects of halothane, isoflurane, and sevoflurane on cross bridges in intact cardiac muscle, electrically stimulated (0.25 Hz, 25 degrees C) right ventricular ferret papillary muscles (n = 14) were subjected to sinusoidal load oscillations (37-182 Hz, 0.2-0.5 mN peak to peak) at the instantaneous self-resonant frequency of the muscle-lever system. At resonance, stiffness is proportional to m * omega(2) (where m is equivalent moving mass and omega is angular frequency). Dynamic stiffness was derived by relating total stiffness to values of passive stiffness at each length during shortening and lengthening. Shortening amplitude and dynamic stiffness were decreased by halothane > isoflurane > or = sevoflurane. At equal peak shortening, dynamic stiffness was higher in halothane or isoflurane in high extracellular Ca(2+) concentration than in control. Halothane and isoflurane increased passive stiffness. The decrease in dynamic stiffness and shortening results in part from direct effects of volatile anesthetics at the level of cross bridges. The increase in passive stiffness caused by halothane and isoflurane may reflect an effect on weakly bound cross bridges and/or an effect on passive elastic elements.

Algorithms↗

Relationship between force and stiffness in muscle fibers after stretch.

The purpose of this study was to evaluate the relationship between force and stiffness after stretch of activated fibers, while simultaneously changing contractility by interfering with the cross-bridge kinetics and muscle activation. Single fibers dissected from lumbrical muscles of frogs were placed at a length 20% longer than the plateau of the force-length relationship, activated, and stretched by 5 and 10% of fiber length (speed: 40% fiber length/s). Experiments were conducted with maximal and submaximal stimulation in Ringer solution and with the addition of 2 and 5 mM of the myosin inhibitor 2,3-butanedione monoxime (BDM) to the solution. The steady-state force after stretch of an activated fiber was higher than the isometric force produced at the corresponding length in all conditions investigated. Lowering the frequency of stimulation decreased the force and stiffness during isometric contractions, but it did not change force enhancement and stiffness enhancement after stretch. Administration of BDM decreased the force and stiffness during isometric contractions, but it increased the force enhancement and stiffness enhancement after stretch. The relationship between force enhancement and stiffness suggests that the increase in force after stretch may be caused by an increase in the proportion of cross bridges attached to actin. Because BDM places cross bridges in a weakly bound, pre-powerstroke state, our results further suggest that force enhancement is partially associated with a recruitment of weakly bound cross bridges into a strongly bound state.

Animals↗

Contractile responses of the rat gastrocnemius and soleus muscles to isotonic resistance exercise.

Male rats were divided into control and weight-trained (WT) groups. WT rats performed squat-type exercises twice daily, 5 days/wk, for 14 wk. They averaged 36 lifts/day, with an average weight of 555 g. Muscle-to-body weight ratio (mg/g) of the soleus (Sol) was not different from control, but it increased 11 and 6% in the gastrocnemius (Gast) and plantaris, respectively (P < 0.05). The normalized twitch tension of the in situ Sol was elevated by 21%, whereas single-skinned type I fibers from the Sol showed an increased rate constant of tension redevelopment (K(tr)) but no other contractile adaptations to WT. In contrast, the Gast type I fibers showed an increase (P < 0.05) in maximal velocity of shortening (25%), peak power (15%), K(tr) (18%), and normalized tension (7%). The K(tr) and normalized tension of the Gast type IIa fibers increased by 24% (P < 0.05) and 12% (P < 0.05), respectively, whereas velocity and power showed a tendency to increase. Fiber size, determined by myosin ATPase histochemistry, was not different for any fiber type from the Gast or Sol. These results indicate that isotonic resistance exercise of the calf targets the Gast (type I and type IIa fibers) and has little effect on the Sol.

Animals↗

Muscle temperature transients before, during, and after exercise measured using an intramuscular multisensor probe.

Seven subjects (1 woman) performed an incremental isotonic test on a Kin-Com isokinetic apparatus to determine their maximal oxygen consumption during bilateral knee extensions (Vo(2 sp)). A multisensor thermal probe was inserted into the left vastus medialis (middiaphysis) under ultrasound guidance. The deepest sensor (tip) was located approximately 10 mm from the femur and deep femoral artery (T(mu 10)), with additional sensors located 15 (T(mu 25)) and 30 mm (T(mu 40)) from the tip. Esophageal temperature (T(es)) was measured as an index of core temperature. Subjects rested in an upright seated position for 60 min in an ambient condition of 22 degrees C. They then performed 15 min of isolated bilateral knee extensions (60% of Vo(2 sp)) on a Kin-Com, followed by 60 min of recovery. Resting T(es) was 36.80 degrees C, whereas T(mu 10), T(mu 25), and T(mu 40) were 36.14, 35.86, and 35.01 degrees C, respectively. Exercise resulted in a T(es) increase of 0.55 degrees C above preexercise resting, whereas muscle temperature of the exercising leg increased by 2.00, 2.37, and 3.20 degrees C for T(mu 10), T(mu 25), and T(mu 40), respectively. Postexercise T(es) showed a rapid decrease followed by a prolonged sustained elevation approximately 0.3 degrees C above resting. Muscle temperature decreased gradually over the course of recovery, with values remaining significantly elevated by 0.92, 1.05, and 1.77 degrees C for T(mu 10), T(mu 25), and T(mu 40), respectively, at end of recovery (P < 0.05). These results suggest that the transfer of residual heat from previously active musculature may contribute to the sustained elevation in postexercise T(es).

Adult↗

Strongly binding myosin crossbridges regulate loaded shortening and power output in cardiac myocytes.

This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during varying levels of Ca(2+) activation. Lowering the [Ca(2+)] slowed shortening velocities, decreased relative power output, and increased the curvature of length traces. We tested the hypothesis that Ca(2+) activation dependence of loaded shortening is determined primarily by strongly binding crossbridges or by [Ca(2+)] per se, which was done by measuring loaded shortening before and after addition of N-ethylmaleimide-conjugated myosin subfragment-1 (NEM-S1), a strongly binding myosin analogue that cooperatively enhances thin filament activation. At fixed [Ca(2+)], NEM-S1 reduced the curvature of length traces and sped loaded shortening velocities. Even when [Ca(2+)] was adjusted so that force was equal with and without NEM-S1, myocyte shortening was faster and exhibited less curvature with NEM-S1. In the presence of NEM-S1, peak relative power output was also significantly greater during activations either at the same [Ca(2+)] or when [Ca(2+)] was adjusted to achieve the same force. Consequently, NEM-S1 eliminated any Ca(2+) dependence of relative power output that is normally observed in cardiac myocytes. These results indicate that strongly binding crossbridges play a significant role in determining loaded shortening and power output and suggest that previously observed Ca(2+) dependence of power output is mediated by alterations in numbers of crossbridges bound to the thin filament.

Animals↗

Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke.

BACKGROUND AND PURPOSE: Alterations of gait cycle and foot-drop on the paretic limb are characteristic of stroke patients. Electromyographic biofeedback treatment has been used in rehabilitation of walking, but results are controversial. We performed gait analysis to evaluate the efficacy of electromyographic biofeedback compared with physical therapy. METHODS: Sixteen patients with ischemic stroke were enrolled in the study. The experimental group (4 men, 4 women) received electromyographic biofeedback treatment together with physical therapy. The control group (5 men, 3 women) was treated with physical therapy only. Clinical and functional evaluations before and after treatment were performed using Canadian Neurological, Adams, Ashworth, Basmajian, and Barthel Index scales. Computerized gait analysis was performed in all patients. RESULTS: Electromyographic biofeedback patients showed significantly increased scores on the Adams scale (P < .05) and Basmajian scale (P < .01). Gait analysis in this group showed a recovery of foot-drop in the swing phase (P < .02) after training. CONCLUSIONS: Our data confirm that the electromyographic biofeedback technique increases muscle strength and improves recovery of functional locomotion in patients with hemiparesis and foot-drop after cerebral ischemia.

Adult↗

Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi.

The intrinsic isometric tone of human isolated intralobar bronchi was evaluated in vitro. Human bronchi (inner diameter, 3 to 12 mm) were obtained from patients undergoing lung resection and from organ donors. The organ donor tissue was studied approximately 24 h after resection, during which time it was shipped to the laboratory in RPMI 1640 medium at 4 degrees C. The bronchi obtained from patients with cancer was placed in the same medium and studied within 4 h of resection. All tissues were suspended in 10-ml organ baths containing oxygenated Krebs' solution at 37 degrees C, at an initial load of 2 g. Tissues were washed every 15 min until they exhibited a stable tension (usually 60 min). Under these conditions the amount of active tension in the bronchi studied on the day of resection averaged 65 +/- 9% of the maximal response to BaCl2 (30 mM), whereas after overnight incubation it averaged 31 +/- 6%. Neither indomethacin nor atropine influenced the intrinsic tone in these tissues. By contrast, the LTD4 antagonists SKF 104353 and ICI 198615 and the histamine H-1 antagonists pyrilamine and chlorpheniramine effectively relaxed the bronchi. The 5' lipoxygenase inhibitor zileuton also produced a small fall in tension. Studies in which pyrilamine was combined with the leukotriene receptor antagonists indicated an additive effect. These results indicate that human bronchial smooth muscle exhibits a high degree of intrinsic tone, averaging more than 50% of available tone in fresh tissues studied in vitro under isometric conditions. The results suggest that this tone is due to the continual production and release of histamine and cysteinyl-leukotrienes.

Bronchi↗

The role of airway smooth muscle during an attack of asthma simulated in vitro.

Excessive narrowing of airways in response to contractile agonists is a characteristic feature of asthma. We hypothesized that airway smooth muscle (ASM) adaptation to short lengths could contribute to exaggerated airway narrowing during an acute attack of asthma by allowing the muscle to regain its ability to generate maximal force at a shortened length. To test this hypothesis we mimicked, in vitro, the sequence of contractile events that would occur during a spontaneous attack of asthma. Trachealis muscle was challenged with carbachol (300 nM, submaximal dose) and allowed to shorten to approximately half of its original length. After 30 min of adaptation at the shortened length in the presence of carbachol, muscle force, amount and rate of shortening in response to electrical stimulation were compared with corresponding values obtained from control experiments during which the ASM was not adapted to the short length. After adaptation at the shortened length the developed force, amount and rate of shortening increased by 1.93 +/- 0.08-, 1.57 +/- 0.12-, and 1.75 +/- 0.2-fold, respectively. Shortening of ASM in response to contractile agonists can lead to adaptation of the muscle to the shortened length that, in turn, can result in further shortening and the potential for airway closure.

Adaptation, Physiological↗