An innovative work-loop calorimeter for in vitro measurement of the mechanics and energetics of working cardiac trabeculae

Taberner, Andrew J.; Han, June‐Chiew; Loiselle, Denis S.; Nielsen, Poul M. F.

doi:10.1152/japplphysiol.00752.2011

Cited by 52 publications

(65 citation statements)

References 27 publications

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“…We have overcome these limitations by constructing a temperature-controlled flow-through muscle calorimeter with exceptionally high thermal resolution. In contrast to previous muscle calorimeter designs (16,36,37), we have used solid-state thermoelectric modules as both temperature sensors and temperature controllers. …”

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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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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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“…Flow microcalorimeters for cardiac muscle have been developed by J. Daut and Elzinga (9) and, most recently, by D. Loiselle and colleagues (39). Our experiments were based on the thermopile methodology recently adapted by Barclay and Widen (49) to measure heat output by papillary muscle of mouse heart.…”

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Mechanical and energetic properties of papillary muscle fromACTCE99K transgenic mouse models of hypertrophic cardiomyopathy

Song

Vikhorev

Kashyap

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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We compared the contractile performance of papillary muscle from a mouse model of hypertrophic cardiomyopathy [α-cardiac actin (ACTC) E99K mutation] with nontransgenic (non-TG) littermates. In isometric twitches, ACTC E99K papillary muscle produced three to four times greater force than non-TG muscle under the same conditions independent of stimulation frequency and temperature, whereas maximum isometric force in myofibrils from these muscles was not significantly different. ACTC E99K muscle relaxed slower than non-TG muscle in both papillary muscle (1.4×) and myofibrils (1.7×), whereas the rate of force development after stimulation was the same as non-TG muscle for both electrical stimulation in intact muscle and after a Ca²⁺ jump in myofibrils. The EC₅₀ for Ca²⁺ activation of force in myofibrils was 0.39 ± 0.33 μmol/l in ACTC E99K myofibrils and 0.80 ± 0.11 μmol/l in non-TG myofibrils. There were no significant differences in the amplitude and time course of the Ca²⁺ transient in myocytes from ACTC E99K and non-TG mice. We conclude that hypercontractility is caused by higher myofibrillar Ca²⁺ sensitivity in ACTC E99K muscles. Measurement of the energy (work + heat) released in actively cycling heart muscle showed that for both genotypes, the amount of energy turnover increased with work done but with decreasing efficiency as energy turnover increased. Thus, ACTC E99K mouse heart muscle produced on average 3.3-fold more work than non-TG muscle, and the cost in terms of energy turnover was disproportionately higher than in non-TG muscles. Efficiency for ACTC E99K muscle was in the range of 11-16% and for non-TG muscle was 15-18%.

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“…In the former case, efficiency is given by the ratio of pressure-volume work to the energetic equivalent of oxygen [81]. In the latter case, efficiency is given by the ratio of force-length work to the sum of work and heat production [82][83][84]. We hope to demonstrate to readers the advantage of studying the diabetic myocardium at these two extreme levels of structural organisation of the heart.…”

Section: Partitioning Of Cardiac Energy Expenditurementioning

confidence: 92%

“…This device [82], which we call a work-loop calorimeter, measures displacement in the order of micrometres, forces in the order of micrograms and heat output in the order of nanowatts. Displacement is achieved by a linear motor and is measured by one arm of a heterodyne laser.…”

Section: The Rat Isolated LV Trabecula Modelmentioning

confidence: 99%

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Assessing the Efficiency of the Diabetic Heart at Subcellular, Tissue and Organ Level

Han¹

2014

J Gen Pract

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In this review, we focus on the diabetic heart rather than the vascular complications of diabetes. Focus is further narrowed to a specific, but widely used, animal model: the diabetic rat heart in which diabetes has been induced by a single injection of streptozotocin. Our experimental approach is primarily biophysical and ranges from measurements made in isolated working whole-hearts, to those made from isolated left-ventricular tissues and mitochondria. Our interest is on the effect of severe diabetes on cardiac energetics, in terms of efficiency of cardiac work performance, ATP synthesis and oxygen consumption. By designing experiments to test the energetic performance of the heart and its trabeculae across a wide range of protocols, we have revealed the dependence of efficiency on afterload. This has allowed us to clarify a long-standing uncertainty in the literature; whereas the diabetic heart is unable to work against high afterloads, it nevertheless retains normal peak efficiency. But a further anomaly has been revealed. Whereas there is no evidence that the diabetic myocardium loses peak mechanical efficiency, its mitochondria demonstrate a decreased P:O ratio -i.e., a decreased bioenergetic efficiency. This decrease is consistent with an increase in the rate of production of reactive oxygen species, together with elevated proton leakage across the inner mitochondrial membrane at near maximal phosphorylating respiration states.Keywords: Cardiac oxygen consumption; Pressure-volume work; Myocardial heat production, Force-length work, Mitochondrial efficiency PreambleReaders of the Journal of General Practice will scarcely need to be reminded that diabetes is a leading cause of death in both the 'developed' and 'developing' world [1]. New Zealand is no exception. We do have something of a unique situation, however, since the burden falls disproportionately on the Maori & Polynesian populations, with both the prevalence and the death rates approaching double those of Pakeha (http://www.maoridiabetes.co.nz/). Given the strong link between obesity and diabetes, the high rates of obesity in New Zealand (31% of adults in 2013) is of increasing concern (http:// www.health.govt.nz/our-work/diseases-and-conditions/obesity/ obesity-key-facts-and-statistics).There have been a number of excellent reviews on the subject of diabetes [2][3][4][5], surely the most unique of which is that authored by Gottlieb [6], dealing with clinical and epidemiological issues. Since we are neither clinicians nor epidemiologists but rather, physiologists, biophysicists and bioengineers, we offer a different point-of-view. Our motivation commences from the knowledge that upwards of 80% of overall morbidity and mortality associated with diabetes is attributable to cardiovascular disease, involving both the arterial/arteriolar system and the myocardium per se. Specifically, we focus on the 'diabetic heart' first described by Rubler et al. [7] from four diabetic patients who had died of diabetic glomerulosclerosis and whose hearts w...

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An innovative work-loop calorimeter for in vitro measurement of the mechanics and energetics of working cardiac trabeculae

Cited by 52 publications

References 27 publications

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

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

Mechanical and energetic properties of papillary muscle fromACTCE99K transgenic mouse models of hypertrophic cardiomyopathy

Assessing the Efficiency of the Diabetic Heart at Subcellular, Tissue and Organ Level

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