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1.
Front Bioeng Biotechnol ; 10: 766748, 2022.
Article in English | MEDLINE | ID: mdl-35265590

ABSTRACT

Distal limb injuries are common in racing horses and track surface properties have been associated with injury risk. To better understand how track surfaces may contribute to equine limb injury, we developed the first 3D computational model of the equine hoof interacting with a racetrack and simulated interactions with model representations of 1) a dirt surface and 2) an all-weather synthetic track. First, a computational track model using the Smoothed Particle Hydrodynamics (SPH) method with a Drucker-Prager (D-P) elastoplastic material model was developed. It was validated against analytical models and published data and then calibrated using results of a custom track testing device applied to the two racetrack types. Second, a sensitivity analysis was performed to determine which model parameters contribute most significantly to the mechanical response of the track under impact-type loading. Third, the SPH track model was coupled to a biomechanical model of the horse forelimb and applied to hoof-track impact for a horse galloping on each track surface. We found that 1) the SPH track model was well validated and it could be calibrated to accurately represent impact loading of racetrack surfaces at two angles of impact; 2) the amount of harrowing applied to the track had the largest effect on impact loading, followed by elastic modulus and cohesion; 3) the model is able to accurately simulate hoof-ground interaction and enables study of the relationship between track surface parameters and the loading on horses' distal forelimbs.

2.
Hum Mov Sci ; 64: 252-273, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30822692

ABSTRACT

Kayak racing performance is known to be dependent on technique, strength and equipment, but the relationship between these factors and performance is not well understood. Complete experimental measures of stroke technique and the interactions between the water and the paddle and the boat are not practical in a racing environment. Instead, simulation using computational fluid dynamics can be used to study this system. A coupled biomechanical-Smoothed Particle Hydrodynamics (B-SPH) model of the kayaking athlete is presented. Verification and validation of the model are confirmed using drag force data from the literature and a spatial resolution study. Using this model and stroke kinematics (developed from the combination of literature data and digitised motion of an amateur level athlete from video), calculations are made of (a) the fluid response to interactions with the paddle and kayak; (b) speed of the kayak; and (c) magnitudes of force and impulse on the paddle and the hands. Key features of the fluid response are related to the loading on the athlete and the speed of the kayak. Perturbations to stroke technique are explored to give new insights into the relationships between technique and racing performance.


Subject(s)
Water Sports/physiology , Athletes , Biomechanical Phenomena/physiology , Computer Simulation , Hand/physiology , Humans , Hydrodynamics , Male , Models, Theoretical , Movement/physiology , Ships , Water
3.
Food Funct ; 9(6): 3202-3219, 2018 Jun 20.
Article in English | MEDLINE | ID: mdl-29775189

ABSTRACT

The stomach is a critical organ for food digestion but it is not well understood how it operates, either when healthy or when dysfunction occurs. Stomach function depends on the timing and amplitude of wall contractions, the fill level and the type of gastric content. Using a coupled biomechanical-Smoothed Particle Hydrodynamics (B-SPH) model, we investigate how gastric discharge is affected by the contraction behaviour of the stomach wall and the viscosity of the content. The results of the model provide new insights into how the content viscosity and the number of compression waves down the length of the stomach affect the mixing within and the discharge rate of the content exiting from the stomach to the duodenum. This investigation shows that the B-SPH model is capable of simulating complicated stomach behaviour. The rate of gastric emptying is found to increase with a smaller period in between contractile waves and to have a nonlinear relationship with content viscosity. Increased resistance to flow into the duodenum is also shown to reduce the rate of emptying. The degree of gastric mixing is found to be insensitive to changes in the period between contractile waves for fluid with a viscosity of water but to be substantially affected by the viscosity of the gastric content.


Subject(s)
Gastric Emptying , Stomach/physiology , Hydrodynamics , Kinetics , Models, Biological , Stomach/chemistry
4.
Food Funct ; 5(11): 2792-805, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25277842

ABSTRACT

A dynamic, three dimensional (3D) computational model that predicts the breakdown of food and the release of tastants and aromas could enhance the understanding of how food is perceived during consumption. This model could also shorten the development process of new foods because many virtual foods could be assessed, and discarded if unsuitable, before any physical prototyping is required. The construction and testing of a complete 3D model of mastication presents many challenges including an accurate representation of: the anatomical movements of the oral cavity (including the teeth, tongue, cheeks and palates), the breakdown behaviour of the food, the interactions between comminuted food and saliva as the bolus is formed, the release and transport of taste and aromas and how these physical and chemical processes are perceived by a person. These challenges are discussed in reference to previous experimental and simulation work and using results of new applications of a coupled biomechanical-smoothed particle hydrodynamics (B-SPH) model. The B-SPH model is demonstrated to simulate several complicated aspects of mastication including: (1) the sensitivity of particle size to changes in the movements of the jaw and tongue; (2) large strain behaviour of food due to softening by heating; (3) interactions between solid and liquid food components; (3) the release of tastants into the saliva; and (4) the transport of tastants to the taste buds. These applications show the possibilities of a model to viably simulate mastication, but highlight the many modelling and experimental challenges that remain.


Subject(s)
Computer Simulation , Mastication/physiology , Models, Biological , Odorants/analysis , Taste , Humans , Imaging, Three-Dimensional , Palate/physiology , Particle Size , Saliva/physiology , Tongue/physiology
5.
J Appl Biomech ; 30(5): 609-18, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24979812

ABSTRACT

The purpose of this study was to determine the pitching effects of buoyancy during all competitive swimming strokes--freestyle, backstroke, butterfly, and breaststroke. Laser body scans of national-level athletes and synchronized multiangle swimming footage were used in a novel markerless motion capture process to produce three-dimensional biomechanical models of the swimming athletes. The deforming surface meshes were then used to calculate swimmer center-of-mass (CoM) positions, center-of-buoyancy (CoB) positions, pitch buoyancy torques, and sagittal plane moments of inertia (MoI) throughout each stroke cycle. In all cases the mean buoyancy torque tended to raise the legs and lower the head; however, during part of the butterfly stroke the instantaneous buoyancy torque had the opposite effect. The swimming strokes that use opposing arm and leg strokes (freestyle and backstroke) had smaller variations in CoM positions, CoB positions, and buoyancy torques. Strokes with synchronized left-right arm and leg movement (butterfly and breaststroke) had larger variations in buoyancy torques, which impacts the swimmer's ability to maintain a horizontal body pitch for these strokes. The methodology outlined in this paper enables the rotational effects of buoyancy to be better understood by swimmers, allowing better control of streamlined horizontal body positioning during swimming to improve performance.


Subject(s)
Athletic Performance/physiology , Competitive Behavior/physiology , Swimming/physiology , Adult , Biomechanical Phenomena , Female , Humans , Male , Models, Biological , Torque , Video Recording
6.
J Biomech ; 47(1): 65-73, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24210848

ABSTRACT

The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal locomotion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle-tendon forces, joint loads and cartilage stresses all increased as locomotion speed increased from walking to trotting and finally cantering. Perturbations to muscle-tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject-specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites of common injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation.


Subject(s)
Cartilage, Articular/physiology , Ligaments/physiology , Locomotion , Metacarpophalangeal Joint/physiology , Weight-Bearing/physiology , Animals , Bone and Bones , Gait , Horses , Joints/physiology , Pressure , Range of Motion, Articular/physiology , Stress, Mechanical , Tendons , Torque
7.
Clin Anat ; 26(4): 522-30, 2013 May.
Article in English | MEDLINE | ID: mdl-23553712

ABSTRACT

The objectives of this study were to investigate the anatomical relationship between the proximal adductor longus (AL) and rectus abdominis muscles and to determine whether unilateral loading of AL results in strain transmission across the anterior pubic symphysis to the contralateral distal rectus sheath. Bilateral dissections were conducted on 10 embalmed cadavers. Strain transfer across the pubic symphysis was examined on seven of these cadavers. An AL contraction was simulated by applying a controlled load in the direction of its proximal tendinous fibers, and the resultant strain in the contralateral distal rectus sheath was measured using a foil-type surface mounted microstrain gage. Adductor longus attached to the antero-inferior aspect of the pubis. In 18 of the 20 limbs, the proximal attachment of AL was tendinous on its superficial surface and muscular on its deep surface. The proximal AL tendon was found in most instances to have secondary communications with structures such as the contralateral distal rectus sheath, pubic symphysis anterior capsule, ilio-inguinal ligament, and contralateral proximal AL tendon. Despite these consistent anatomical observations, strain measured in the contralateral distal rectus sheath upon unilateral loading of the proximal AL varied considerably between cadavers. Measured strain had an average ± 1SD of 0.23 ± 0.43%. The proximal attachment of AL contributes to an anatomical pathway across the anterior pubic symphysis that is likely required to withstand the transmission of large forces during multidirectional athletic activities. This anatomical relationship may be a relevant factor in explaining the apparent vulnerability of the AL and rectus abdominis attachments to injury.


Subject(s)
Muscle, Skeletal/anatomy & histology , Pubic Symphysis/anatomy & histology , Rectus Abdominis/anatomy & histology , Thigh/anatomy & histology , Aged , Aged, 80 and over , Biomechanical Phenomena , Cadaver , Female , Humans , Ligaments/anatomy & histology , Male , Tendons/anatomy & histology , Weight-Bearing
8.
J Exp Biol ; 215(Pt 17): 2980-91, 2012 Sep 01.
Article in English | MEDLINE | ID: mdl-22875767

ABSTRACT

Few quantitative data exist to describe the activity of the distal muscles of the equine forelimb during locomotion, and there is an incomplete understanding of the functional roles of the majority of the forelimb muscles. Based on morphology alone it would appear that the larger proximal muscles perform the majority of work in the forelimb, whereas the smaller distal muscles fulfil supplementary roles such as stabilizing the joints and positioning the limb for impact with the ground. We measured the timing and amplitude of the electromyographic activity of the intrinsic muscles of the forelimb in relation to the phase of gait (stance versus swing) and the torque demand placed on each joint during walking, trotting and cantering. We found that all forelimb muscles, except the extensor carpi radialis (ECR), were activated just prior to hoof-strike and deactivated during stance. Only the ECR was activated during swing. The amplitudes of muscle activation typically increased as gait speed increased. However, the amplitudes of muscle activation were not proportional to the net joint torques, indicating that passive structures may also contribute significantly to torque generation. Our results suggest that the smaller distal muscles help to stabilize the forelimb in early stance, in preparation for the passive structures (tendons and ligaments) to be stretched. The distal forelimb muscles remain active throughout stance only during canter, when the net torques acting about the distal forelimb joints are highest. The larger proximal muscles activate in a complex coordination to position and stabilize the shoulder and elbow joints during ground contact.


Subject(s)
Forelimb/physiology , Horses/physiology , Locomotion/physiology , Muscles/physiology , Animals , Biomechanical Phenomena/physiology , Electromyography , Gait/physiology , Joints/physiology , Physical Conditioning, Animal , Rotation , Time Factors , Torque , Weight-Bearing/physiology
9.
J Exp Biol ; 213(Pt 23): 3998-4009, 2010 Dec 01.
Article in English | MEDLINE | ID: mdl-21075941

ABSTRACT

Storage and utilization of strain energy in the elastic tissues of the distal forelimb of the horse is thought to contribute to the excellent locomotory efficiency of the animal. However, the structures that facilitate elastic energy storage may also be exposed to dangerously high forces, especially at the fastest galloping speeds. In the present study, experimental gait data were combined with a musculoskeletal model of the distal forelimb of the horse to determine muscle and joint contact loading and muscle-tendon work during the stance phase of walking, trotting and galloping. The flexor tendons spanning the metacarpophalangeal (MCP) joint - specifically, the superficial digital flexor (SDF), interosseus muscle (IM) and deep digital flexor (DDF) - experienced the highest forces. Peak forces normalized to body mass for the SDF were 7.3±2.1, 14.0±2.5 and 16.7±1.1 N kg(-1) in walking, trotting and galloping, respectively. The contact forces transmitted by the MCP joint were higher than those acting at any other joint in the distal forelimb, reaching 20.6±2.8, 40.6±5.6 and 45.9±0.9 N kg(-1) in walking, trotting and galloping, respectively. The tendons of the distal forelimb (primarily SDF and IM) contributed between 69 and 90% of the total work done by the muscles and tendons, depending on the type of gait. The tendons and joints that facilitate storage of elastic strain energy in the distal forelimb also experienced the highest loads, which may explain the high frequency of injuries observed at these sites.


Subject(s)
Elasticity/physiology , Horses/physiology , Joints/physiology , Locomotion/physiology , Muscles/physiology , Animals , Biomechanical Phenomena/physiology , Forelimb/physiology , Ligaments/physiology , Models, Anatomic , Tendons/physiology , Weight-Bearing/physiology
10.
Cell Calcium ; 47(4): 378-86, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20227109

ABSTRACT

Sepsis is associated with ventricular dysfunction and increased incidence of atrial and ventricular arrhythmia however the underlying pro-arrhythmic mechanisms are unknown. Serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are elevated during sepsis and affect Ca2+ regulation. We investigated whether pro-inflammatory cytokines disrupt cellular Ca2+ cycling leading to reduced contractility, but also increase the probability of pro-arrhythmic spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). Isolated rat ventricular myocytes were exposed to TNF-alpha (0.05 ng ml(-1)) and IL-1beta (2 ng ml(-1)) for 3 hr and then loaded with fura-2 or fluo-3 to record the intracellular Ca2+ concentration ([Ca2+](i)). Cytokine treatment decreased the amplitude of the spatially averaged Ca2+ transient and the associated contraction, induced asynchronous Ca2+ release during electrical stimulation, increased the frequency of localized Ca2+ release events, decreased the SR Ca2+ content and increased the frequency of spontaneous Ca2+ waves at any given cytoplasmic Ca2+. These data suggest that TNF-alpha and IL-1beta increase the SR Ca2+ leak from the SR, which contributes to the depressed Ca2+ transient and contractility. Increased susceptibility to spontaneous SR Ca2+ release may contribute to arrhythmias in sepsis as the resulting Ca2+ extrusion via NCX is electrogenic, leading to cell depolarisation.


Subject(s)
Arrhythmias, Cardiac/immunology , Interleukin-1beta/pharmacology , Muscle Cells/drug effects , Sepsis/immunology , Tumor Necrosis Factor-alpha/pharmacology , Animals , Arrhythmias, Cardiac/complications , Calcium Signaling/drug effects , Calcium Signaling/immunology , Cells, Cultured , Disease Susceptibility , Heart Ventricles/pathology , Male , Muscle Cells/immunology , Muscle Cells/metabolism , Muscle Cells/pathology , Myocardial Contraction/immunology , Rats , Rats, Wistar , Sarcoplasmic Reticulum/metabolism , Sepsis/complications
11.
J Theor Biol ; 257(2): 279-91, 2009 Mar 21.
Article in English | MEDLINE | ID: mdl-19135456

ABSTRACT

Volatile anaesthetics such as halothane, isoflurane and sevoflurane inhibit membrane currents contributing to the ventricular action potential. Transmural variation in the extent of current blockade induces differential effects on action potential duration (APD) in the endocardium and epicardium which may be pro-arrhythmic. Biophysical modelling techniques were used to simulate the functional impact of anaesthetic-induced blockade of membrane currents on APD and effective refractory period (ERP) in rat endocardial and epicardial cell models. Additionally, the transmural conduction of excitation waves in 1-dimensional cell arrays, the tissue's vulnerability to arrhythmogenesis and dynamic behaviour of re-entrant excitation in 2-dimensional cell arrays were studied. Simulated anaesthetic exposure reduced APD and ERP in both epicardial and endocardial cell models. The reduction in APD was greater in endocardial than epicardial cells, reducing transmural APD dispersion consistent with experimental data. However, the transmural ERP dispersion was augmented. All three anaesthetics increased the width of the tissue's vulnerable window during which a premature stimulus could induce unidirectional conduction block but only halothane reduced the critical size of ventricular substrates necessary to initiate and sustain re-entrant excitation. All three anaesthetics accelerated the rate of re-entrant excitation waves, but only halothane prolonged the lifespan of re-entry. These data illustrate in silico, that modest changes in ion channel conductance abbreviate rat ventricular APD and ERP, reduce transmural APD dispersion, but augment transmural ERP dispersion. These changes collectively enhance the propensity for arrhythmia generation and provide a substrate for re-entry circuits with a longer half life than in control conditions.


Subject(s)
Anesthetics/pharmacology , Arrhythmias, Cardiac/chemically induced , Computer Simulation , Heart Conduction System/drug effects , Models, Cardiovascular , Action Potentials/drug effects , Action Potentials/physiology , Animals , Arrhythmias, Cardiac/physiopathology , Endocardium/drug effects , Endocardium/physiopathology , Halothane/pharmacology , Heart Conduction System/physiopathology , Isoflurane/pharmacology , Methyl Ethers/pharmacology , Myocytes, Cardiac/drug effects , Pericardium/drug effects , Pericardium/physiopathology , Rats , Sevoflurane
12.
J Mol Cell Cardiol ; 42(3): 582-9, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17234206

ABSTRACT

Age and hypertension contribute significantly to cardiac morbidity and mortality, however the importance of each during the progression of hypertrophy is unclear. This investigation examined the effect of age and hypertension on Ca(2+) handling in rat ventricular myocytes by comparing a genetic model of hypertension and cardiac hypertrophy (spontaneously hypertensive rat, SHR) with its normotensive control (Wistar-Kyoto rat, WKY) at 5 and 8 months of age. Experiments were performed on single left ventricular myocytes isolated from SHR or WKY hearts. Intracellular Ca(2+) was measured optically using fura-2 or fluo-3. SHR myocytes had a significantly larger cell width and volume and a significantly decreased cell length/width ratio at 5 and 8 months compared to normotensive controls. Age had no effect on cell length, width, volume or the length/width ratio. Ca(2+) transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) content and contraction amplitude were unaffected by age or hypertrophy. However at 8 months the contribution of the SR to Ca(2+) uptake during relaxation decreased, with a concomitant increase in the contribution of Na(+)/Ca(2+) exchanger (NCX) function to relaxation, in SHR and WKY myocytes. The incidence of non-synchronous SR Ca(2+) release decreased with age but not hypertrophy in SHR and WKY myocytes. These results show that the changes in Ca(2+) handling observed during progression of mild hypertrophy in SHR are the same as those that occur during ageing in normotensive control animals and can, therefore, be ascribed to maturation rather than hypertrophy.


Subject(s)
Aging/physiology , Calcium/metabolism , Heart Ventricles/metabolism , Hypertrophy/metabolism , Sarcoplasmic Reticulum/metabolism , Sodium-Calcium Exchanger/metabolism , Animals , Biological Transport , Heart Ventricles/pathology , Hypertrophy/pathology , Male , Rats
13.
Pflugers Arch ; 453(4): 463-9, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17066274

ABSTRACT

Changes in cellular calcium (Ca(2+)) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca(2+). The present study was performed to investigate whether changes in the distribution of I (Ca) between the surface and t-tubule membranes might contribute to the altered Ca(2+) handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I (Ca) in the presence and absence of t-tubules. Membrane capacitance and I (Ca) were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I (Ca) both decreased and were no longer significantly different in the two cell types. The density of I (Ca) was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I (Ca) is unchanged in SHR myocytes compared to WKY controls; I (Ca) density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I (Ca), so that the density of I (Ca) at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca(2+) release in the SHR at this stage of compensated hypertrophy.


Subject(s)
Calcium Channels/physiology , Calcium/metabolism , Myocytes, Cardiac/physiology , Analysis of Variance , Animals , Body Weight/physiology , Calcium Channels/metabolism , Cell Size , Cells, Cultured , Male , Membrane Potentials/physiology , Microscopy, Confocal , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Patch-Clamp Techniques , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Species Specificity
14.
Anesthesiology ; 105(1): 58-64, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16809995

ABSTRACT

BACKGROUND: Halothane has been reported to sensitize Ca(2+) release from the sarcoplasmic reticulum (SR), which is thought to contribute to its initial positive inotropic effect. However, little is known about whether isoflurane or sevoflurane affect the SR Ca(2+) release process, which may contribute to the inotropic profile of these anesthetics. METHODS: Mild Ca(2+) overload was induced in isolated rat ventricular myocytes by increase of extracellular Ca(2+) to 2 mM. The resultant Ca(2+) transients due to spontaneous Ca(2+) release from the SR were detected optically (fura-2). Cells were exposed to 0.6 mM anesthetic for a period of 4 min, and the frequency and amplitude of spontaneous Ca(2+) transients were measured. RESULTS: Halothane caused a temporary threefold increase in frequency and decreased the amplitude (to 54% of control) of spontaneous Ca(2+) transients. Removal of halothane inhibited spontaneous Ca release before it returned to control. In contrast, sevoflurane initially inhibited frequency of Ca(2+) release (to 10% of control), whereas its removal induced a burst of spontaneous Ca(2+) release. Isoflurane had no significant effect on either frequency or amplitude of spontaneous Ca(2+) release on application or removal. Sevoflurane was able to ameliorate the effects of halothane on the frequency and amplitude of spontaneous Ca(2+) release both on application and wash-off. CONCLUSIONS: Application of halothane and removal of sevoflurane sensitize the SR Ca(2+) release process (and vice versa on removal). Sevoflurane reversed the effects of halothane, suggesting they may act at the same subcellular target on the SR.


Subject(s)
Calcium/antagonists & inhibitors , Halothane/pharmacology , Methyl Ethers/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Animals , Calcium/metabolism , Heart Ventricles/drug effects , Heart Ventricles/metabolism , In Vitro Techniques , Rats , Sevoflurane
15.
Am J Physiol Heart Circ Physiol ; 288(5): H2431-8, 2005 May.
Article in English | MEDLINE | ID: mdl-15615841

ABSTRACT

Hypertension-induced cardiac hypertrophy alters the amplitude and time course of the systolic Ca2+ transient of subepicardial and subendocardial ventricular myocytes. The present study was designed to elucidate the mechanisms underlying these changes. Myocytes were isolated from the left ventricular subepicardium and subendocardium of 20-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY; control). We monitored intracellular Ca2+ using fluo 3 or fura 2; caffeine (20 mmol/l) was used to release Ca2+ from the sarcoplasmic reticulum (SR), and Ni2+ (10 mM) was used to inhibit Na+/Ca2+ exchange (NCX) function. SHR myocytes were significantly larger than those from WKY hearts, consistent with cellular hypertrophy. Subepicardial myocytes from SHR hearts showed larger Ca2+ transient amplitude and SR Ca2+ content and less Ca2+ extrusion via NCX compared with subepicardial WKY myocytes. These parameters did not change in subendocardial myocytes. The time course of decline of the Ca2+ transient was the same in all groups of cells, but its time to peak was shorter in subepicardial cells than in subendocardial cells in WKY and SHR and was slightly prolonged in subendocardial SHR cells compared with WKY subendocardial myocytes. It is concluded that the major change in Ca2+ cycling during compensated hypertrophy in SHR is a decrease in NCX activity in subepicardial cells; this increases SR Ca2+ content and hence Ca2+ transient amplitude, thus helping to maintain the strength of contraction in the face of an increased afterload.


Subject(s)
Calcium/metabolism , Cardiomegaly/metabolism , Hypertension/metabolism , Myocytes, Cardiac/metabolism , Sodium/metabolism , Adaptation, Physiological/physiology , Animals , Cardiomegaly/physiopathology , Endocardium/cytology , Heart Ventricles/cytology , Male , Myocardial Contraction/physiology , Pericardium/cytology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Sarcoplasmic Reticulum/metabolism
16.
Cardiovasc Res ; 65(1): 167-76, 2005 Jan 01.
Article in English | MEDLINE | ID: mdl-15621044

ABSTRACT

OBJECTIVE: Previous work suggests that modification of sarcoplasmic reticulum (SR) function may contribute to the cardioprotective effect of halothane during ischaemia and reperfusion. The aim of this study was to investigate the effects of halothane on spontaneous Ca(2+) release from the sarcoplasmic reticulum (Ca(2+) sparks and waves). METHODS: Rat atrial myocytes were permeabilized with saponin and perfused with solutions approximating to the intracellular milieu and containing fluo-3. SR Ca(2+) release was detected using confocal microscopy. RESULTS: In the presence of 5 mM ATP, halothane (0.25-2 mM) had no significant effect on the amplitude or frequency of spontaneous Ca(2+) waves. However, in the presence of 0.05 mM ATP, halothane (0.25-2 mM) induced a concentration-dependent decrease in the amplitude and an increase in the frequency of spontaneous Ca(2+) waves, e.g., 1 mM halothane decreased the amplitude by 34.7+/-3.5% (n=9) and increased the frequency by 67+/-19.9% (n=7). In the presence of 5 mM ATP, 1 mM halothane had no significant effect on the amplitude or frequency of Ca(2+) sparks. When [ATP] was reduced to 0.05 mM, Ca(2+) spark frequency decreased by 67.9+/-14% and the amplitude increased by 27.5+/-4.9% (n=13). Subsequent introduction of halothane (0.5-1 mM) induced a transient burst of Ca(2+) sparks, consistent with ryanodine receptor (RyR) activation. Further experiments showed that the decrease in Ca(2+) spark frequency following ATP depletion was associated with a progressive increase in the SR Ca(2+) content over 1-2 min. This rise in SR Ca(2+) content did not occur when 1 mM halothane was present during ATP depletion. CONCLUSIONS: These data suggest that the sensitivity of the RyR to activation by halothane increases at low [ATP]. In metabolically impaired cells, halothane would be expected to lessen any rise in SR Ca(2+) content and to reduce the amplitude of spontaneous Ca(2+) release. These effects of halothane are considered in relation to the events that occur during ischaemia and reperfusion.


Subject(s)
Adenosine Triphosphate/metabolism , Anesthetics/pharmacology , Calcium/metabolism , Halothane/pharmacology , Myocytes, Cardiac/metabolism , Sarcoplasmic Reticulum/metabolism , Animals , Heart Atria , Microscopy, Confocal , Myocytes, Cardiac/drug effects , Rats , Sarcoplasmic Reticulum/drug effects
17.
Anesth Analg ; 99(6): 1615-1622, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15562042

ABSTRACT

Halothane, isoflurane, and sevoflurane abbreviate ventricular action potential duration (APD), and for halothane this effect is greater in the subendocardium than in the subepicardium. In this study we investigated mechanisms underlying the regional effects of these anesthetics on APD. The effect of 0.6 mM halothane, isoflurane, and sevoflurane on the action potential, L-type Ca(2+) current, transient outward K(+) current (I(to)), and steady-state current was recorded in rat left ventricular subendocardial and subepicardial myocytes. Halothane and isoflurane (but not sevoflurane) reduced APD significantly (P < 0.05), more in subendocardial than subepicardial myocytes. Peak L-type Ca(2+) current did not differ between regions and, compared with control, was reduced significantly in both regions by 40% (P < 0.001), 20% (P < 0.001), and 12% (P < 0.01) by halothane, isoflurane, and sevoflurane, respectively. I(to) was greater in subepicardial (3.95 +/- 0.29 nA) than subendocardial (1.12 +/- 0.05 nA) myocytes. In subepicardial myocytes, peak I(to) was reduced significantly by halothane (P < 0.01) and isoflurane (P < 0.05) (by 8% and 7%, respectively) but was unaffected by sevoflurane. No significant reduction of I(to) was observed in subendocardial myocytes with the three anesthetics. The steady-state current was increased significantly (P < 0.05), but the extent of this increase did not differ between the two regions or among the three anesthetics. Therefore, greater inhibition of I(to) in subepicardial than subendocardial myocytes by halothane and isoflurane could underlie their transmural effects on APD.


Subject(s)
Anesthetics, Inhalation , Calcium Channels/drug effects , Halothane , Isoflurane , Methyl Ethers , Myocytes, Cardiac/metabolism , Potassium Channels/metabolism , Action Potentials/drug effects , Animals , Electrophysiology , Endocardium/cytology , Endocardium/drug effects , Endocardium/metabolism , Heart Ventricles/cytology , Heart Ventricles/drug effects , Heart Ventricles/metabolism , Kinetics , Myocytes, Cardiac/drug effects , Patch-Clamp Techniques , Pericardium/cytology , Pericardium/drug effects , Pericardium/metabolism , Rats , Rats, Wistar , Sevoflurane
18.
Cardiovasc Res ; 62(3): 529-37, 2004 Jun 01.
Article in English | MEDLINE | ID: mdl-15158145

ABSTRACT

OBJECTIVE: Recent work has suggested that Na(+)/Ca(2+) exchange (NCX) and L-type Ca(2+) current (I(Ca)) are located predominantly in the t-tubules of cardiac ventricular myocytes, which therefore represent a microdomain for the regulation of intracellular Na(+) (Na(i)) and Ca(2+) (Ca(i)). The aim of this study was to investigate the role of the t-tubules in the response of Ca(i) and contraction to interventions that alter the transsarcolemmal Na(+)gradient. METHODS: Enzymatically isolated and detubulated Wistar rat ventricular myocytes were investigated using fluorescence microscopy and optical detection of cell length. RESULTS: In unstimulated cells, spontaneous contractile activity increased when extracellular [Na(+)] was decreased or strophanthidin (100 microM) was added to the bathing solution, but the increase was significantly smaller in detubulated cells than in control cells. In electrically stimulated cells, strophanthidin increased Na(i) to a similar extent in normal and detubulated cells, although the associated increase in Ca(2+) transient amplitude and contraction were significantly smaller in detubulated cells. Similarly, tetrodotoxin (TTX, 10 microM) attenuated the Ca(2+) transient and contraction less in detubulated than in control cells. Increasing stimulation rate (0.05-1 Hz) caused little change or a small increase in contraction amplitude in control cells, but a significant decrease in contraction amplitude in detubulated cells, although the change of Na(i) caused by increasing stimulation rate from 0 to 1 Hz was not significantly different in the two cells types. CONCLUSION: It is concluded that although some Na/K ATPase, NCX and Na(+)channel activity is present on the surface membrane, the t-tubules play a major role in the modulation of contraction via NCX, allowing changes of the transsarcolemmal Na(+)gradient to be translated into changes of Ca(i).


Subject(s)
Muscle Fibers, Skeletal , Myocytes, Cardiac/metabolism , Sarcolemma/metabolism , Animals , Calcium/metabolism , Cell Size/drug effects , Cells, Cultured , Heart Ventricles , Male , Microscopy, Fluorescence , Myocytes, Cardiac/drug effects , Rats , Rats, Wistar , Sodium/metabolism , Stimulation, Chemical , Strophanthidin/pharmacology , Tetrodotoxin/pharmacology
19.
Anesth Analg ; 98(4): 1013-1016, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15041590

ABSTRACT

UNLABELLED: Previous investigations of the effects of potent opioid analgesics on the heart have concentrated on effects on contraction magnitude and time course, but little is known about their effects on cytosolic Ca(2+) regulation in cardiac tissue. In this study, we sought to assess the effects of alfentanil on contractility and the cytosolic Ca(2+) transient in ventricular myocytes isolated from the rat ventricle by enzymatic dispersion. Cells were loaded with fura-2 and electrically stimulated at 1 Hz, and Ca(2+) transients and contractions were recorded optically at 30 degrees C. Alfentanil 10(-8) and 10(-7) M had no effect on the magnitude or time course of contraction or the cytosolic Ca(2+) transient. In contrast, 10(-6) M alfentanil induced a significant (P < 0.001) positive inotropic effect, increasing the mean (+/-SEM) unloaded shortening from 7.3 +/- 1.3 microm to 8.7 +/- 1.4 microm (an increase of 20%), with no change in the cytosolic Ca(2+) transient. Myofilament Ca(2+) sensitivity was significantly (P = 0.027) increased by 10(-6) M alfentanil but unaffected at 10(-7) M alfentanil. These data show that 10(-6) M alfentanil, a concentration close to the maximum clinical free plasma concentration, induced a positive inotropic effect due to sensitization of the myofilaments to Ca(2+) rather than to modified cytosolic Ca(2+) regulation. IMPLICATIONS: Alfentanil, at concentrations achieved in clinical practice, increased contraction in ventricular cells by a mechanism involving an increase in the sensitivity of the contractile apparatus to Ca(2+).


Subject(s)
Alfentanil/pharmacology , Anesthetics, Intravenous/pharmacology , Calcium/metabolism , Cytosol/metabolism , Myocytes, Cardiac/metabolism , Animals , Calcium Signaling/drug effects , Cytosol/drug effects , Electric Stimulation , Fluorescent Dyes , Fura-2 , Heart Ventricles/cytology , Heart Ventricles/drug effects , Heart Ventricles/metabolism , In Vitro Techniques , Myocardial Contraction/drug effects , Myocytes, Cardiac/drug effects , Rats
20.
J Physiol ; 556(Pt 2): 481-94, 2004 Apr 15.
Article in English | MEDLINE | ID: mdl-14724216

ABSTRACT

Recent studies have proposed that release of calcium from the sarcoplasmic reticulum (SR) modulates the spontaneous activity of the sinoatrial node (SAN). Previously we have shown that several calcium regulatory proteins are expressed at a lower level in the centre of the SAN compared with the periphery. Such differences may produce heterogeneity of intracellular calcium handling and pacemaker activity across the SAN. Selective isolations showed that the centre of the SAN is composed of smaller cells than the periphery. Measurements of cytosolic calcium in spontaneously beating cells showed that diastolic calcium, systolic calcium, the calcium transient amplitude and spontaneous rate were greater in larger (likely to be peripheral) cells compared with smaller (likely to be central) SAN cells. The SR calcium content was greater in larger cells, although SR recruitment was more efficient in smaller cells. The sodium-calcium exchanger and sarcolemmal calcium ATPase had a lower activity and the exchanger was responsible for a larger proportion of sarcolemmal calcium extrusion in smaller cells compared with larger cells. Ryanodine had a greater effect on the spontaneous calcium transient in larger cells compared with smaller cells, and slowed pacemaker activity in larger cells but not smaller cells, thus abolishing the difference in cycle length. This study shows heterogeneity of intracellular calcium regulation within the SAN and this contributes to differences in pacemaker activity between cells from across the SAN. The smallest central cells of the leading pacemaker region of the SAN do not require SR calcium for spontaneous activity nor does disruption of the SR alter pacemaking in these primary pacemaker cells.


Subject(s)
Calcium/metabolism , Sinoatrial Node/cytology , Sinoatrial Node/physiology , Aniline Compounds/pharmacology , Animals , Biological Clocks/physiology , Buffers , Cell Size , Cytosol/metabolism , Fluorescent Dyes/pharmacology , In Vitro Techniques , Rabbits , Ryanodine/pharmacology , Sarcoplasmic Reticulum/metabolism , Xanthenes/pharmacology
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