Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

Han, June‐Chiew; Tran, Kenneth; Taberner, Andrew J.; Nickerson, David; Kirton, Robert; Nielsen, Poul; Ward, Marie‐Louise; Nash, Martyn P.; Crampin, Edmund J.; Loiselle, Denis S.

doi:10.1113/jphysiol.2012.228965

Cited by 13 publications

(13 citation statements)

References 70 publications

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“…We note that the fading of twitch duration after longer than 20 minutes of formamide washout is consistent with that observed in thinner trabeculae 31 (cross‐sectional area of 0.057 mm 2 ± 0.010 mm 2 ), which contradicts the hypothesis that formamide‐detubulation is insufficient in thicker trabeculae used in this study (0.089 mm 2 ± 0.015 mm 2 ). We deduce instead that twitch duration returned to the value that corresponded to the new steady‐state stress value, that is, twitch duration depends on stress 52 . This deduction is supported by two lines of evidence from our results.…”

Section: Discussionsupporting

confidence: 77%

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

et al. 2020

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Aim Altered organization of the transverse‐tubular network is an early pathological event occurring even prior to the onset of heart failure. Such t‐tubular remodelling disturbs the synchrony and signalling between membranous and intracellular ion channels, exchangers, receptors and ATPases essential in the dynamics of excitation‐contraction coupling, leading to ionic abnormality and mechanical dysfunction in heart disease progression. In this study, we investigated whether a disrupted t‐tubular network has a direct effect on cardiac mechano‐energetics. Our aim was to understand the fundamental link between t‐tubular remodelling and impaired energy metabolism, both of which are characteristics of heart failure. We thus studied healthy tissue preparations in which cellular processes are not altered by any disease event. Methods We exploited the “formamide‐detubulation” technique to acutely disrupt the t‐tubular network in rat left‐ventricular trabeculae. We assessed the energy utilization by cellular Ca2+ cycling and by crossbridge cycling, and quantified the change of energy efficiency following detubulation. For these measurements, trabeculae were mounted in a microcalorimeter where force and heat output were simultaneously measured. Results Following structural disorganization from detubulation, muscle heat output associated with Ca2+ cycling was reduced, indicating impaired intracellular Ca2+ homeostasis. This led to reduced force production and heat output by crossbridge cycling. The reduction in force‐length work was not paralleled by proportionate reduction in the heat output and, as such, energy efficiency was reduced. Conclusions These results reveal the direct energetic consequences of disrupted t‐tubular network, linking the energy disturbance and the t‐tubular remodelling typically observed in heart failure.

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Section: Discussionsupporting

confidence: 77%

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

et al. 2020

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“…Vice versa, theoretical models can help in projecting from macro- to micro-scales, such as to assess the effects of ‘gross’ mechanical deformations of ventricular tissue on coronary blood flow, 98 energy demand, 99 or cell-level stress–strain behaviour. 100 They can also aid the process of linking whole-organ observations, such as obtained with optical mapping of functional parameters, to underlying tissue and cell behaviour, 101–104 as illustrated below.…”

Section: Wet/dry Reduction: From Macro To Micromentioning

confidence: 99%

Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

Quinn

Kohl

2013

Cardiovascular Research

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Since the development of the first mathematical cardiac cell model 50 years ago, computational modelling has become an increasingly powerful tool for the analysis of data and for the integration of information related to complex cardiac behaviour. Current models build on decades of iteration between experiment and theory, representing a collective understanding of cardiac function. All models, whether computational, experimental, or conceptual, are simplified representations of reality and, like tools in a toolbox, suitable for specific applications. Their range of applicability can be explored (and expanded) by iterative combination of ‘wet’ and ‘dry’ investigation, where experimental or clinical data are used to first build and then validate computational models (allowing integration of previous findings, quantitative assessment of conceptual models, and projection across relevant spatial and temporal scales), while computational simulations are utilized for plausibility assessment, hypotheses-generation, and prediction (thereby defining further experimental research targets). When implemented effectively, this combined wet/dry research approach can support the development of a more complete and cohesive understanding of integrated biological function. This review illustrates the utility of such an approach, based on recent examples of multi-scale studies of cardiac structure and mechano-electric function.

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“…Studies of force production simultaneous with heat output of cardiac muscle require the use of isolated tissue preparations such as small papillary muscles (2-4, 12, 26, 34) or trabeculae carneae (17)(18)(19)(20)(21) as they are sufficiently small to avoid muscle anoxia (14). The use of these tissue preparations, which have approximately one-dimensional arrangements of myocytes, simplifies the interpretation of measurements.…”

Section: We Have Developed a New Muscle Calorimeter Which Has Enablementioning

confidence: 99%

A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature

Johnston

Han

Ruddy

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Johnston CM, Han JC, Ruddy BP, Nielsen PM, Taberner AJ. A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature. Am J Physiol Heart Circ Physiol 309: H318 -H324, 2015. First published May 22, 2015; doi:10.1152/ajpheart.00194.2015.-Isolated ventricular trabeculae are the most common experimental preparations used in the study of cardiac energetics. However, the experiments have been conducted at subphysiological temperatures. We have overcome this limitation by designing and constructing a novel calorimeter with sufficiently high thermal resolution for simultaneously measuring the heat output and force production of isolated, contracting, ventricular trabeculae at body temperature. This development was largely motivated by the need to better understand cardiac energetics by performing such measurements at body temperature to relate tissue performance to whole heart behavior in vivo. Our approach uses solid-state thermoelectric modules, tailored for both temperature sensing and temperature control. The thermoelectric modules have high sensitivity and low noise, which, when coupled with a multilevel temperature control system, enable an exceptionally high temperature resolution with a noise-equivalent power an order of magnitude greater than those of other existing muscle calorimeters. Our system allows us to rapidly and easily change the experimental temperature without disturbing the state of the muscle. Our calorimeter is useful in many experiments that explore the energetics of normal physiology as well as pathophysiology of cardiac muscle. muscle energetics; microcalorimetry; heat production NEW & NOTEWORTHY We have developed a new muscle calorimeter, which has enabled the first simultaneous measurements of the force and heat output of isolated, actively contracting, cardiac trabeculae at body temperature. This was achieved by the use of thermoelectric modules for high-resolution temperature sensing and precise temperature control.MEASUREMENTS OF THE ENERGETICS of cardiac muscle under controlled experimental conditions, and in particular at body temperature, enable better understanding of cardiac muscle function in health and disease. Studies of force production simultaneous with heat output of cardiac muscle require the use of isolated tissue preparations such as small papillary muscles (2-4, 12, 26, 34) or trabeculae carneae (17-21) as they are sufficiently small to avoid muscle anoxia (14). The use of these tissue preparations, which have approximately one-dimensional arrangements of myocytes, simplifies the interpretation of measurements. Although these tissue studies have improved our understanding of myocardial energetics, previous experiments have been performed only at subphysiological temperatures, typically 10°C below that of body temperature (3,5,10,11,13,23,25,26,28,30,31). One exception is the study by Widén (39), who made simultaneous force and heat measurements in mouse papillary muscles at body temperature. H...

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Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling

Cited by 13 publications

References 70 publications

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

Disruption of transverse‐tubular network reduces energy efficiency in cardiac muscle contraction

Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature

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