Active Muscle Contraction Research Articles

Relationship between the increase of effectiveness indexes and the increase of muscular efficiency with cycling power

We determined the index of effectiveness (IE), as defined by the ratio of the tangential (effective force) to the total force applied on the pedals, using a new method proposed by Mornieux et al. (J Biomech, 2005), while simultaneously measuring the muscular efficiency during sub-maximal cycling tests of different intensities. This allowed us to verify whether part of the changes in muscular efficiency could be explained by a better orientation of the force applied on the pedals. Ten subjects were asked to perform an incremental test to exhaustion, starting at 100 W and with 30 W increments every 5 min, at 80 rpm. Gross (GE) and net (NE) efficiencies were calculated from the oxygen uptake and W(Ext) measurements. From the three-dimensional force's measurements, it was possible to measure the total force (F(Tot)), including the effective (F(Tang)) and ineffective force (F (Rad + Lat)). IE has been determined as the ratio between F(Tang) and F(Tot), applied on the pedals for three different time intervals, i.e., during the full revolution (IE(360 degrees)), the downstroke phase (IE(180 degrees Desc)) and the upstroke phase (IE(180 degrees Asc)). IE(360 degrees) and IE(180 degrees Asc) were significantly correlated with GE (r = 0.79 and 0.66, respectively) and NE (r = 0.66 and 0.99, respectively). In contrast, IE(180 degrees Desc) was not correlated to GE or to NE. From a mechanical point of view, during the upstroke, the subject was able to reduce the non-propulsive forces applied by an active muscle contraction, contrary to the downstroke phase. As a consequence, the term 'passive phase', which is currently used to characterize the upstroke phase, seems to be obsolete. The IE(180 degrees Asc) could also explain small variations of GE and NE for a recreational group.

An anatomically based patient-specific finite element model of patella articulation: towards a diagnostic tool

A 3D anatomically based patient-specific finite element (FE) model of patello-femoral (PF) articulation is presented to analyse the main features of patella biomechanics, namely, patella tracking (kinematics), quadriceps extensor forces, surface contact and internal patella stresses. The generic geometries are a subset from the model database of the International Union of Physiological Sciences (IUPS) (http://www.physiome.org.nz) Physiome Project with soft tissue derived from the widely used visible human dataset, and the bones digitised from an anatomically accurate physical model with muscle attachment information. The models are customised to patient magnetic resonance images using a variant of free-form deformation, called 'host-mesh' fitting. The continuum was solved using the governing equation of finite elasticity, with the multibody problem coupled through contact mechanics. Additional constraints such as tissue incompressibility are also imposed. Passive material properties are taken from the literature and implemented for deformable tissue with a non-linear micro-structurally based constitutive law. Bone and cartilage are implemented using a 'St-Venant Kirchoff' model suitable for rigid body rotations. The surface fibre directions have been estimated from anatomy images of cadaver muscle dissections and active muscle contraction was based on a steady-state calcium-tension relation. The 3D continuum model of muscle, tendon and bone is compared with experimental results from the literature, and surgical simulations performed to illustrate its clinical assessment capabilities (a Maquet procedure for reducing patella stresses and a vastus lateralis release for a bipartite patella). Finally, the model limitations, issues and future improvements are discussed.

Referred Pain From the Trochlear Region in Tension‐Type Headache: A Myofascial Trigger Point From the Superior Oblique Muscle

Tension-type headache (TTH) is a prototypical headache in which myofascial trigger points (MTrPs) can play an important role. To our knowledge, MTrPs in the muscle tissues of the trochlear region, ie, the superior oblique muscle (SOM), have not been previously mentioned, and a referred pain pattern from this region has never been reported. To describe the referred pain from the trochlear area based on the examination of MTrPs in the SOM in patients with episodic and chronic TTH (CTTH). A blinded, controlled study. The trochlear region was examined in 15 patients with CTTH, 15 patients with episodic TTH (ETTH), and 15 control subjects. Referred pain elicited by different maneuvers performed during manual palpation, ie, maintained pressure, active muscle contraction, and stretching of the muscle, was assessed with a visual analogue scale. Patients with ETTH were examined on days when they were headache-free, whereas CTTH patients were examined on days in which headache intensity was less than 4 points on a 10-cm horizontal visual analogue scale. Eighty-six percent of patients with CTTH and 60% with ETTH had referred pain that originated from MTrPs in the SOM, while only 27% of the controls reported referred pain. This pain was perceived as a deep ache located at the retro-orbital region, sometimes extending to the supra-orbital region or the homo-lateral forehead. Pain intensity was greater in CTTH patients than in ETTH patients or control subjects (P < .001). MTrPs in the SOM may evoke a typical referred pain pattern in patients with TTH. The presence of a myofascial disorder in the trochlear region might contribute to the pathogenesis of TTH.

Aesthetic surgery – pertinent papers 2002–2003: A personal view

Aesthetic surgery – pertinent papers 2002–2003: A personal view

Medial surface dynamics of anin vivocanine vocal fold during phonation

Quantitative measurement of the medial surface dynamics of the vocal folds is important for understanding how sound is generated within the larynx. Building upon previous excised hemilarynx studies, the present study extended the hemilarynx methodology to the in vivo canine larynx. Through use of an in vivo model, the medial surface dynamics of the vocal fold were examined as a function of active thyroarytenoid muscle contraction. Data were collected using high-speed digital imaging at a sampling frequency of 2000 Hz, and a spatial resolution of 1024 x 1024 pixels. Chest-like and fry-like vibrations were observed, but could not be distinguished based on the input stimulation current to the recurrent laryngeal nerve. The subglottal pressure did distinguish the registers, as did an estimate of the thyroarytenoid muscle activity. Upon quantification of the three-dimensional motion, the method of Empirical Eigenfunctions was used to extract the underlying modes of vibration, and to investigate mechanisms of sustained oscillation. Results were compared with previous findings from excised larynx experiments and theoretical models.

Other movement disorders

It is helpful to think of most movement disorders (other than akinetic, rigid and ataxic disorders) as forms of dystonia, chorea, tremor, tics or myoclonus. Dystonia is a sustained muscle contraction leading to repetitive movements or abnormal postures. Chorea takes the form of involuntary, abrupt, irregular and random movements, usually of the face, hands and feet. Tremor is a rhythmic oscillation of a body part produced by alternating or synchronous contraction of antagonistic muscles. Tics are rapid, brief jerks, usually of the head and arms. They can be suppressed for short periods at the expense of increasing tension and distress to the patient. Myoclonic jerks are brief, sudden, shock-like movements caused by active muscular contraction. Sudden pauses of muscular activity are termed ‘asterixis’; this is the basis of the ‘flapping tremor’ of various encephalopathic states. Most drug-induced movement disorders are caused by dopamine receptor-blocking agents. Hemifacial spasm may be mistaken for focal epilepsy or focal dystonia. The cause is usually microvascular compression of the facial nerve in the posterior cranial fossa; occasionally, there is a mass lesion in the cerebellopontine angle.

A novel technique to measure active tendon forces: application to the subscapularis tendon

This paper describes the design and use of a novel system for quantification of active tendon forces. An arthroscopically implantable force probe (AIFP) was inserted arthroscopically into the subscapularis tendon of the shoulder in vivo. The output response of this device was calibrated in situ with known forces applied to the tendon using an arthroscopic technique. On recovery of motor control following interscalene regional anaesthesia, the force within the tendon during active muscle contraction was measured. The AIFP was then retrieved through an arthroscopic portal. The technique showed that the subscapularis may produce forces of 250 N during maximum internal rotation of the shoulder.

Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration?

Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES, and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 +/- 14.8 SD (p < 0.0001 vs DDM 14.9 +/- 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 +/- 5.7 SD (p < 0.0001 vs DDM 25.7 +/- 23.7 SD); the mean percentile fat area is 2.1 +/- 2.4 SD (p < 0.001 vs DDM 12.8 +/- 12.1 SD); and the mean percentile connective tissue area is 3.6 +/- 4.6 SD (p < 0.001 vs DDM 61.6 +/- 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter smaller than 10 microm, while the FES-trained subjects have more that 50% of myofibers larger than 30 microm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.

Biomechanical mechanism for transitions in phase and frequency of arm and leg swing during walking.

As humans increase walking speed, there are concurrent transitions in the frequency ratio between arm and leg movements from 2:1 to 1:1 and in the phase relationship between the movements of the two arms from in-phase to out-of-phase. Superharmonic resonance of a pendulum with monofrequency excitation had been proposed as a potential model for this phenomenon. In this study, an alternative model of paired pendulums with multiple-frequency excitations is explored. It was predicted that the occurrence of the concurrent transitions was a function of (1) changes in the magnitude ratio of shoulder accelerations at step and stride frequencies that accompany changes in walking speed and (2) proximity of these frequencies to the natural resonance frequencies of the arms modeled as a pair of passive pendulums. Model predictions were compared with data collected from 14 healthy young subjects who were instructed to walk on a treadmill. Walking speeds were manipulated between 0.18 and 1.52 m/s in steps of 0.22 m/s. Kinematic data for the arms and shoulders were collected using a 3D motion analysis system, and simulations were conducted in which the movements of a double-pendulum system excited by the accelerations at the suspension point were analyzed to determine the extent to which the arms acted as passive pendulums. It was confirmed that the acceleration waveforms at the shoulder are composed primarily of stride and step frequency components. Between the shoulders, the stride frequency components were out-of-phase, while the step frequency components were in-phase. The amplitude ratio of the acceleration waveform components at the step and stride frequencies changed as a function of walking speed and were associated with the occurrence of the transitions. Simulation results using these summed components as excitatory inputs to the double-pendulum system were in agreement with actual transitions in 80% of the cases. The potential role of state-dependent active muscle contraction at shoulder joints on the occurrence of the transitions was discussed. Due to the tendency of arm movements to stay in the vicinity of their primary resonance frequency, these active muscle forces were hypothesized to function as escapements that created limit cycle oscillations at the shoulder's resonant frequency.

Validation of a head-neck computer model for whiplash simulation.

A head-neck computer model was comprehensively validated over a range of rear-impact velocities using experiments conducted by the same group of authors in the same laboratory. Validations were based on mean +/- 1 standard deviation response curves, i.e. corridors. Global head-neck angle, segmental angle and local facet joint regional kinematic responses from the model fell within experimental corridors. This was true for all impact velocities (1.3, 1.8 and 2.6 m s(-1)). The non-physiological S-curvature lasted approximately 100 ms. The present, comprehensively validated model can be used to conduct parametric studies and investigate the effects of factors such as active sequential and parallel muscle contractions, thoracic ramping and local tissue strain responses, as a function of cervical level, joint region and impact velocity in whiplash injury assessment.

Myogenesis contributes to functional electrical stimulation (fes)‐induced recovery of myofiber excitability and mass of human long‐term denervated muscles in spinal cord injury (SCI)

Many months after SCI, when an irreversible injury involves lower motoneurons, severe atrophy of human muscle is complicated by fibrosis and fat substitution (denervated, degenerated muscle, DDM). We will describe the effects of long‐term lower motoneuron denervation on human muscle and present the structural results of muscle trained using FES. Antibody for embryonic myosin demonstrates that sustained myogenesis occurs in human DDM. By electron microscopy we studied: a) the overall structure of fibers and myofibrils in long‐term DDM, including the effects of FES, and b) the structure and localization of calcium release units, or triads, the structure deputed to activate muscle contraction during excitation‐contraction coupling (ECC). The poor excitability of human long‐term DDM fibers during the first stages of FES training could be explained in terms of spatial disorder of both the ECC and contractile apparati. The structural studies are extremely encouraging since they demonstrate that FES training is effective in reverting long‐term DDM atrophy and in maintaining the trophic state of the recovered myofibers.

Systolic ventricular filling.

The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles involved in this action. This contraction occurs during the last part of classical systole and the first part of diastole. Therefore, the most important part of ventricular diastole (i.e. the rapid filling phase), in which it receives >70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment. We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function.

Cervical pregnancy after in vitro fertilization and embryo transfer successfully treated with methotrexate and intracervical injection of vasopressin

Cervical pregnancy after in vitro fertilization and embryo transfer successfully treated with methotrexate and intracervical injection of vasopressin

Cervical pregnancy after in vitro fertilization and embryo transfer successfully treated with methotrexate and intracervical injection of vasopressin.

(2004). Cervical pregnancy after in vitro fertilization and embryo transfer successfully treated with methotrexate and intracervical injection of vasopressin. Acta Obstetricia et Gynecologica Scandinavica: Vol. 83, No. 1, pp. 112-114.

Anterior glenohumeral force/translation behavior with and without rotator cuff contraction during clinical stability testing

Objective. Measure stiffness of the glenohumeral joint during clinical laxity testing with and without muscular contraction of the Internal rotators. Design. Cross-sectional study of normal shoulders. Background. Clinical examination for shoulder instability is based on subjective impression, and is only performed passively. Our study presents a method for quantitative clinical examination of the shoulder under both passive and active muscle contraction conditions. We hypothesized that in a normal shoulder, contraction of the internal rotators will increase the stiffness of the glenohumeral joint, effectively constraining the head of the humerus against anterior directed forces. Methods. Ten subjects were instrumented with electromagnetic sensors to record glenohumeral linear displacements. A mini-force transducer recorded forces applied to subjects during anterior drawer testing (forced anterior glenohumeral displacement), which was performed passively, and during isometric contraction of internal rotators. Results. Only mild contraction of the internal rotators is needed to significantly increase the stiffness to anterior directed forces. Greater muscular activation does not result in further increased stiffness. Conclusion. Objective measurement of glenohumeral stiffness during passive and active muscular contraction may be useful for evaluating the capacity of rotator cuff muscles to stabilize the shoulder. The concept of more strength is better, for rotator cuff strengthen programs is questioned. Relevance The method presented in this study may have useful applications as a diagnostic tool for discriminating dysfunctional rotator cuff activation, as an outcome measure for surgery and rehabilitation, and as a didactic tool for teaching shoulder examination by providing immediate objective feedback to the examiner.

A Mathematical Model for Estimating Muscle Tension in vivo during Esophageal Bolus Transport

We present a model of esophageal wall muscle mechanics during bolus transport with which the active and “passive” components of circular muscle tension are separately extracted from concurrent manometric and videofluoroscopic data. Local differential equations of motion are integrated across the esophageal wall to yield global equations of equilibrium which relate total tension within the esophageal wall to intraluminal pressure and wall geometry. To quantify the “passive” (i.e. inactive) length-tension relationships, the model equations are applied to a region of the esophagus in which active muscle contraction is physiologically inhibited. Combining the global equations with space–time-resolved intraluminal pressure measured manometrically and videofluoroscopic geometry data, the passive model is used to separate active and “passive” components of esophageal muscle tension during bolus transport. The model is of general applicability to probe basic muscle mechanics including the space–time stimulation of circular muscle, the relationship between longitudinal muscle tension and longitudinal muscle shortening, and the contribution of the collagen matrix surrounding muscle fibers to passive tension during normal human esophageal bolus transport and in pathology. Example calculations of normal esophageal function are given where active tone is found to extend only over a short intrabolus segment near the bolus tail and segmental regions of active muscle squeeze are demonstrated.

Invited commentary

Cardiomyoplasty lives on in its legacy. While not currently a viable clinical option, the lessons and insights learned from cardiomyoplasty has influenced a new generation of passive devices to treat heart failure. Before cardiomyoplasty, surgeons avoided wrapping or restraining the heart. However, cardiomyoplasty showed that wrapping the heart, at least with a biological material, was tolerated; restrictive filling did not occur. Many believe that the primary benefit of cardiomyoplasty was due to this passive wrap, which slowed progressive left ventricular enlargement. In heart failure, as the ventricle enlarges, wall stress, the afterload on the cardiomyocytes, increases, leading to a decrease in the mechanical efficiency of the heart, more oxygen is consumed for the same amount of work. By limiting the increase in left ventricular end-diastolic volume, the passive property of cardiomyoplasty decreased peak left ventricular wall stress. As compared to controls, myocardial oxygen consumption decreased and the mechanical efficiency of the heart increased [1Patel H.J. Pilla J.J. Polidori D.J. Sutton M.S. Lankford E.B. Acker M.A. Long-term dynamic cardiomyoplasty improves chronic and acute myocardial energetics in a model of left ventricular dysfunction.Circulation. 1998; 98: II346-II351PubMed Google Scholar]. Kawaguchi’s article [2Kawaguchi O. Huang Y.F. Yuasa T. Shirota K. Carrington R.A.J. Hunyor S.N. Sparing of myocardial oxygen by cardiomyoplasty implications for mechanical direct cardiac compression.Ann Thorac Surg. 2002; Google Scholar] shows an additional systolic advantage of cardiomyoplasty previously underappreciated, namely that active systolic contraction of the latissimus muscle, dynamic cardiomyoplasty, further increased the mechanical efficiency (the external work/MVO2) of the heart. Thus passive devices may not reproduce the benefits of dynamic cardiomyoplasty. The simple assumption that the sole benefit was derived from the passive properties of cardiomyoplasty may not be true. Similar to cardiomyoplasty in initial clinical trials, restrictive filling problems have not occurred with the Acorn CorCap [3Oz M.C. Konetz W.F. Kleber F.X. Mohr F.W. Gummert J.F. Ostermeyer J. Las M. Raman J. Acker M.A. Smedira N. Global surgical experience with the Acorn Cardiac Support Device.Proceedings of the 82nd Annual Meeting of the American Association of Thoracic Surgery. 2002; 236Google Scholar]. Additionally, experimental studies show that compared to controls, passive left ventricular restraining [4Pilla J.J. Brockman D.J. Blom A.S. Yuan Q. Acker M.A. Passive ventricular constraint improves myocardial energetics in a model of heart failure secondary to acute infarction.Proceedings of the 82nd Annual Meeting of the American Association of Thoracic Surgery. 2002; 76Google Scholar] or reshaping [5Inoue M. McCarthy P.M. Takagaki M. Ochia Y. Doi K. Faber C. Dessoffy R. Kopcak Jr, M.W. Fukamachi K. Energetic advantages of device-based left ventricular shape change.ASAIO J. 2002; 48 (abstract): 136Crossref Google Scholar] devices increase the mechanical efficiency of the left ventricle. However, Kawaguchi’s article leaves us wondering if devices that restrain left ventricular end-diastolic volume and additionally provide some active systolic support may not be a better solution, and also serve as the true lesson learned from dynamic cardiomyoplasty.

Documentary of inter and intra-fractional prostate motion using self-moving CT scanner combined with linear accelerator, and cine-MRI: what moves the prostate

Documentary of inter and intra-fractional prostate motion using self-moving CT scanner combined with linear accelerator, and cine-MRI: what moves the prostate

Kinematics of the buccal mass during swallowing based on magnetic resonance imaging in intact, behaving Aplysia californica.

A novel magnetic resonance imaging interface has been developed that makes it possible to image movements in intact, freely moving subjects. We have used this interface to image the internal structures of the feeding apparatus (i.e. the buccal mass) of the marine mollusc Aplysia californica. The temporal and spatial resolution of the resulting images is sufficient to describe the kinematics of specific muscles of the buccal mass and the internal movements of the main structures responsible for grasping food, the radula and the odontophore. These observations suggest that a previously undescribed feature on the anterior margin of the odontophore, a fluid-filled structure that we term the prow, may aid in opening the jaw lumen early in protraction. Radular closing during swallowing occurs near the peak of protraction as the radular stalk is pushed rapidly out of the odontophore. Retraction of the odontophore is enhanced by the closure of the lumen of the jaws on the elongated odontophore, causing the odontophore to rotate rapidly towards the esophagus. Radular opening occurs after the peak of retraction and without the active contraction of the protractor muscle 12 and is due, in part, to the movement of the radular stalk into the odontophore. The large variability between responses also suggests that the great flexibility of swallowing responses may be due to variability in neural control and in the biomechanics of the ingested food and to the inherent flexibility of the buccal mass.

Progression of Heart Failure

The cardiac ryanodine receptor (RyR2)/Ca2+ release channel on the sarcoplasmic reticulum (SR) is regulated by evolutionarily highly conserved signaling pathways that control excitation-contraction (EC) coupling in the heart. Phosphorylation of RyR2 by cAMP-dependent protein kinase (PKA) plays a key role in regulating the channel in response to stress via activation of the sympathetic nervous system (the “fight-or-flight response”).1 Maladaptive PKA hyperphosphorylation of RyR2 in failing hearts alters channel function, which may cause depletion of SR Ca2+ and diastolic release of SR Ca2+. This can initiate delayed afterdepolarizations that trigger ventricular arrhythmias.1 Mutations in RyR2 recently have been identified in patients with catecholaminergic induced sudden cardiac death (SCD).2–4⇓⇓ There may be a direct link between the PKA hyperphosphorylation of RyR2 that occurs during the progression of heart failure and fatal cardiac arrhythmias. Regulation of cardiac EC coupling by the release of Ca2+ from the SR via RyR2 in cardiomyocytes, known as Ca2+-induced Ca2+ release (CICR), has been appreciated for more than a decade.5,6⇓ Furthermore, it is well known that the amplitude of the Ca2+ transient generated by SR Ca2+ release determines contractile force in cardiomyocytes. The systems that regulate SR Ca2+ release include: (1) the triggers (predominantly Ca2+ influx through the voltage-gated Ca2+ channel on the plasma membrane); (2) the SR Ca2+ release channel or type 2 RyR2; and (3) the SR Ca2+ reuptake pump (SERCA2a) and its regulator phospholamban. These systems (trigger, release, and reuptake) are modulated by signaling pathways, including the β-adrenergic receptor (β-AR) signaling pathway (ie, phosphorylation by PKA). Activation of the sympathetic nervous system in response to stress results in elevation of cAMP levels and activation of PKA. Phosphorylation of RyR2 may not correlate directly …