3‐Dimensional configuration of perimysial collagen fibres in rat cardiac muscle at resting and extended sarcomere lengths

Hanley, Peter J.; Young, Alistair A.; LeGrice, Ian J.; Edgar, Stephen; Loiselle, Denis S.

doi:10.1111/j.1469-7793.1999.0831s.x

Cited by 79 publications

(67 citation statements)

References 32 publications

(55 reference statements)

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“…The right ventricle was opened, and free running trabeculae (diameter Ͻ400 m) were excised and subsequently transferred to the calorimeter. These preparations were shown recently to be composed chiefly of myocytes accompanied by parallel perimysial collagen fibers (13). After a trabecula was mounted in the calorimeter, the solution was then changed to a standard physiological salt solution containing (mM) 121 NaCl, 5 KCl, 2 CaCl 2, 0.8 MgCl2, 1 NaH2PO4, 24 NaHCO3, and 10 glucose (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

Ray

Noll

Daut

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of long-chain (LC) fatty acids on rate of heat production (heat rate) and mitochondrial membrane potential (⌬⌿) of intact guinea pig cardiac muscle were investigated at 37°C. Heat rate of ventricular trabeculae was measured with microcalorimetry, and ⌬⌿ was monitored in isolated ventricular myocytes with either JC-1 or tetramethylrhodamine ethyl ester (TMRE). Methyl-␤-cyclodextrin was used as fatty acid carrier. Application of 400 M oleate or linoleate increased resting heat rate by ϳ30% and ϳ25%, respectively. When LC fatty acid was supplied as sole metabolic substrate, resting heat rate was decreased by 3-mercaptopropionic acid. In TMRE-loaded myocytes, neither 40-80 M oleate nor 40 M linoleate affected ⌬⌿. At a higher concentration (400 M) both oleate and linoleate increased TMRE fluorescence by ϳ20% of maximum, obtained using 2,4-dinitrophenol (100 M), indicating a depolarization of the inner mitochondrial membrane. We conclude that LC fatty acids, at sufficiently high concentration, increase heat rate and decrease ⌬⌿ in intact cardiac muscle, consistent with a protonophoric uncoupling action. These effects may contribute to the high metabolic rate after reperfusion of postischemic myocardium. mitochondrial membrane potential; microcalorimetry IN CARDIAC MUSCLE, the resting (basal) level of metabolism is extraordinarily high, accounting for 25-30% of the metabolic rate of mechanically active muscle (3,4,9,12,22,29). Although the origin of this high resting metabolic rate is unknown, it has been shown to be sensitive to metabolic substrate (4, 9). This is well illustrated with pyruvate, which has been shown to increase resting rate of heat production (4) and oxygen consumption (9) of isolated cardiac muscle preparations.In isolated mitochondrial preparations, long-chain (LC) fatty acids have been shown convincingly to uncouple oxidative phosphorylation (27,31). Whether this uncoupling action manifests in intact cardiac muscle is not known (14,35). This unresolved issue is important because LC fatty acids are the major metabolic substrates of the heart and, furthermore, they are known to accumulate in high concentrations during ischemia (6, 33). The aims of the present study were to determine the effects of LC fatty acids on both resting heat rate and mitochondrial membrane potential (⌬⌿) of intact cardiac muscle. METHODS Isolation of trabeculae and microcalorimetry.Guinea pigs (200-300 g) were anesthetized with 3-4% isoflurane in oxygen and then decapitated with a guillotine. The heart was rapidly excised and perfused with dissecting solution containing (mM) 105 NaCl, 15 KCl, 2 CaCl 2, 1 MgCl2, 1 NaH2PO4, 24 NaHCO3, 20 2,3-butanedione monoxime, and 10 glucose. The solution was equilibrated with 95% O2-5% CO2, and the pH was 7.4. The right ventricle was opened, and free running trabeculae (diameter Ͻ400 m) were excised and subsequently transferred to the calorimeter. These preparations were shown recently to be composed chiefly of myocytes accompanied by parallel perimysial collagen fibers (13). Af...

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Section: Methodsmentioning

confidence: 99%

Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

Ray

Noll

Daut

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Ventricular tissue has a complex three-dimensional microstructural architecture that varies with location and depth across the ventricular wall (6,26,35,44). Although trabeculae are often treated as homologous to ventricular tissue (20,23), they have a simpler microstructure, consisting of axially aligned myocytes and large parallel perimysial collagen fibers (20). More complex microstructures may show strain softening behavior.…”

Section: Strain Softeningmentioning

confidence: 99%

Strain softening is not present during axial extensions of rat intact right ventricular trabeculae in the presence or absence of 2,3-butanedione monoxime

Kirton¹,

Taberner²,

Young³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Strain softening is not present during axial extensions of rat intact right ventricular trabeculae in the presence or absence of 2,3-butanedione monoxime. Am J Physiol Heart Circ Physiol 286: H708-H715, 2004; 10.1152/ajpheart.00580.2003.-Recent studies of passive myocardial mechanics have shown that strain softening behavior is present during both inflation of isolated whole rat hearts and shearing of tissue blocks taken from the left ventricular free wall in pigs. Strain softening is typically manifested by a stiffer forceextension relation in the first deformation cycle relative to subsequent cycles and is distinguished from viscoelasticity by a lack of recovery of stiffness, even after several hours of rest. The causes of this behaviour are unknown. We investigated whether strain softening is observed in uniaxial extensions of intact, viable, rat right ventricular (RV) cardiac trabeculae. Stretch and release cycles of 5%, 10%, and 15% muscle length were applied at a constant velocity at 26°C. Muscles were tested in random order in the presence and absence of 50 mM 2,3-butanedione monoxime (BDM). Whereas strain softening was displayed by nonviable trabeculae, it was not observed in viable preparations undergoing physiologically relevant extensions whether in the presence or absence of BDM. BDM also had no effect on passive compliance. There was a reversible increase of muscle compliance between the first and subsequent cycles, with recovery after 30 s of rest, independent of the presence of BDM. We conclude that strain softening is neither intrinsic to viable rat RV trabeculae nor influenced by BDM and that passive trabeculae compliance is not altered by the addition of BDM. cardiac muscle; passive tissue compliance; stress-strain relations; stretch THE PASSIVE MECHANICAL PROPERTIES of cardiac muscle are of fundamental importance, as they influence the velocity of shortening (8), limit the volume of blood that enters the heart, and play a major role in determining the stroke volume (5). It is crucial for our understanding of the mechanisms by which cardiovascular disease changes the mechanical properties of the diseased heart to have a sound understanding of the passive material properties of healthy cardiac tissue. Impaired diastolic filling can also manifest as diastolic heart failure in patients with apparently normal systolic function.However, the passive tension-length relationship is difficult to determine at the tissue level due to the complex threedimensional geometry of the heart and the laminar microstructure of myocardium (6,26,35,44). To reduce the anatomic and microstructural complexities present in a whole heart model, mechanical experiments are often conducted on smaller samples of myocardial tissue. Such experiments range from biaxial testing of myocardial sheets (10) to uniaxial testing of ventricular strips (33), papillary muscles (4, 16), cardiac trabeculae (42), isolated myocytes (5, 17), myofibrils (29), actin filaments (30), and individual titin molecules (25). Anisotropic, nonlinear, l...

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“…The response F d includes titin and the effects of any residual endomysial collagen on the cells [23], but does not include the effects of thick collagen bundles which limit the operating range of the heart to a maximal sarcomere length of 2.35 µm [22], blood vessels, fibroblasts and other components of the myocardium. The constitutive law represents all of these elements in a lumped description of the passive response of myocardium.…”

Section: Multi-scale Modelmentioning

confidence: 99%

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Land

Park-Holohan

Smith

et al. 2017

Journal of Molecular and Cellular Cardiology

110

147

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Experimental data from human cardiac myocytes at body temperature is crucial for a quantitative understanding of clinically relevant cardiac function and development of whole-organ computational models. However, such experimental data is currently very limited. Specifically, important measurements to characterize changes in tension development in human cardiomyocytes that occur with perturbations in cell length are not available. To address this deficiency, in this study we present an experimental data set collected from skinned human cardiac myocytes, including the passive and viscoelastic properties of isolated myocytes, the steady-state force calcium relationship at different sarcomere lengths, and changes in tension following a rapid increase or decrease in length, and after constant velocity shortening. This data set is, to our knowledge, the first characterization of length and velocity-dependence of tension generation in human skinned cardiac myocytes at body temperature.We use this data to develop a computational model of contraction and passive viscoelasticity in human myocytes. Our model includes troponin C kinetics, tropomyosin kinetics, a three-state crossbridge model that accounts for the distortion of crossbridges, and the cellular viscoelastic response. Each component is parametrized using our experimental data collected in human cardiomyocytes at body temperature. Furthermore we are able to confirm that properties of length-dependent activation at 37• C are similar to other species, with a shift in calcium sensitivity and increase in maximum tension. We revise our model of tension generation in the skinned isolated myocyte to replicate reported tension traces generated in intact muscle during isometric tension, to provide a model of human tension generation for multi-scale simulations. This process requires changes to calcium sensitivity, cooperativity, and crossbridge transition rates. We apply this model within multi-scale simulations of biventricular cardiac function and further refine the parametrization within the whole organ context, based on obtaining a healthy ejection fraction. This process reveals that crossbridge cycling rates differ between skinned myocytes and intact myocytes.

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3‐Dimensional configuration of perimysial collagen fibres in rat cardiac muscle at resting and extended sarcomere lengths

Cited by 79 publications

References 32 publications

Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

Strain softening is not present during axial extensions of rat intact right ventricular trabeculae in the presence or absence of 2,3-butanedione monoxime

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

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