Resolving an inconsistency in the estimation of the energy for excitation of cardiac muscle contraction.

In the excitation of muscle contraction, calcium ions interact with transmembrane transporters. This process is accompanied by energy consumption and heat liberation. To quantify this activation energy or heat in the heart or cardiac muscle, two non-pharmacological approaches can be used.

Uncovering cross-bridge properties that underlie the cardiac active complex modulus using model linearisation techniques.

The properties underlying cardiac cross-bridge kinetics can be characterised by a muscle's active complex modulus. While the complex modulus can be described by a series of linear transfer functions, the biophysical mechanisms underlying these components are represented inconsistently among existing cross-bridge models. To address this, we examined the properties commonly implemented in cross-bridge models using model linearisation techniques and assessed their contributions to the complex modulus.

Cardiac efficiency and Starling's Law of the Heart.

The formulation by Starling of The Law of the Heart states that 'the [mechanical] energy of contraction, however measured, is a function of the length of the muscle fibre'. Starling later also stated that 'the oxygen consumption of the isolated heart … is determined by its diastolic volume, and therefore by the initial length of its muscular fibres'. This phrasing has motivated us to extend Starling's Law of the Heart to include consideration of the efficiency of contraction.

Slower shortening kinetics of cardiac muscle performing Windkessel work-loops increase mechanical efficiency.

Conventional experimental methods for studying cardiac muscle in vitro often do not expose the tissue preparations to a mechanical impedance that resembles the in vivo hemodynamic impedance dictated by the arterial system. That is, the afterload in work-loop contraction is conventionally simplified to be constant throughout muscle shortening, and at a magnitude arbitrarily defined. This conventional afterload does not capture the time-varying interaction between the left ventricle and the arterial system.

Cross-bridge thermodynamics in pulmonary arterial hypertensive right-ventricular failure.

Right-ventricular (RV) failure is an event consequent to pathological RV hypertrophy commonly resulting from pulmonary arterial hypertension. This pathology is well characterized by RV diastolic dysfunction, impaired ejection, and reduced mechanical efficiency. However, whether the dynamic stiffness and cross-bridge thermodynamics in the failing RV muscles are compromised remains uncertain.

Heat production in quiescent cardiac muscle is length, velocity and muscle dependent: Implications for active heat measurement.

New Findings: What is the central question of this study? Intracellular energetic processes in quiescent cardiac muscle release 'basal' heat; during contraction, a much larger amount of 'active' heat is also produced. Previously, measurement challenges have constrained researchers to assume that basal heat rate remains constant during contraction and shortening. Is this assumption correct? What is the main finding and its importance? We show that basal heat rate is modulated by the extent and velocity of muscle shortening.

Right-sided heart failure is also associated with transverse tubule remodeling in the left ventricle.

Right-sided heart failure is a common consequence of pulmonary arterial hypertension. Overloading the right ventricle results in right ventricular hypertrophy, which progresses to failure in a process characterized by impaired Ca dynamics and force production that is linked with transverse (t)-tubule remodeling. This also unloads the left ventricle, which consequently atrophies.

Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function.

Increased heart size is a major risk factor for heart failure and premature mortality. Although abnormal heart growth subsequent to hypertension often accompanies disturbances in mechano-energetics and cardiac efficiency, it remains uncertain whether hypertrophy is their primary driver. In this study, we aimed to investigate the direct association between cardiac hypertrophy and cardiac mechano-energetics using isolated left-ventricular trabeculae from a rat model of primary cardiac hypertrophy and its control.

Thermodynamic inconsistency disproves the Suga-Sagawa theory of cardiac energetics.

The theory proposed by Suga and Sagawa, encompassing the concepts of 'time-varying elastance', 'pressure-volume area' and 'isoefficiency', has been widely applied in cardiac research - albeit not without contention. In this Review, we commence with a brief history of striated muscle energetics as a prelude to re-visiting the Suga-Sagawa Theory. We conclude our discussion by including recent insights into the fundamental flaw underlying the metabolic component of the Theory.

Compensating for changes in heart muscle resting heat production in a microcalorimeter.

The heat production of cardiac muscle, determined by calorimetry, can be used as a measure of cardiac metabolism. However, heat produced while a muscle is actively-shortening, thereby performing force-length work, comprises both active and basal metabolic processes. In this paper, we present a method for post-experimental processing of calorimetric measurements of muscle heat production, that uncovers and compensates for the measured basal heat rate during work.

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

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.

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship.

In experimental studies on cardiac tissue, the end-systolic force-length relation (ESFLR) has been shown to depend on the mode of contraction: isometric or isotonic. The isometric ESFLR is derived from isometric contractions spanning a range of muscle lengths while the isotonic ESFLR is derived from shortening contractions across a range of afterloads. The ESFLR of isotonic contractions consistently lies below its isometric counterpart.

An Equivocal Final Link - Quantitative Determination of the Thermodynamic Efficiency of ATP Hydrolysis - Sullies the Chain of Electric, Ionic, Mechanical and Metabolic Steps Underlying Cardiac Contraction.

Each beat of the heart completes the final step in a sequence of events commencing with electrical excitation-triggered release of Ca from the sarcoplasmic reticulum which, in turn, triggers ATP-hydrolysis-dependent mechanical contraction. Given that is inherently detail-independent, the heart can be thus be viewed as a mechanical pump - the generator of pressure that drives blood through the systemic and pulmonary circulations. The beat-to-beat pressure-volume work (W) of the heart is relatively straightforward to measure experimentally.

Energetics Equivalent of the Cardiac Force-Length End-Systolic Zone: Implications for Contractility and Economy of Contraction.

We have recently demonstrated the existence of a region on the cardiac mechanics stress-length plane, which we have designated "The cardiac end-systolic zone." The zone is defined as the area on the pressure-volume (or stress-length) plane within which all stress-length contraction profiles reach their end-systolic points. It is enclosed by three boundaries: the isometric end-systolic relation, the work-loop (shortening) end-systolic relation, and the zero-active stress isotonic end-systolic relation.

Energy expenditure for isometric contractions of right and left ventricular trabeculae over a wide range of frequencies at body temperature.

We studied the energy expenditure of isometric contractions using both right-ventricular (RV) and left-ventricular (LV) trabeculae isolated from the rat heart. The energy expenditure under isometric contraction presents entirely as heat liberation. Preparations were challenged to perform at various rates of energy demand while accounting for their inevitable time-dependent decline of performance.

Solving a century-old conundrum underlying cardiac force-length relations.

In the late 19th century, Otto Frank presented a diagram (Frank O. Z Biol 37: 483-526, 1899) showing that cardiac end-systolic pressure-volume relations are dependent on the mode of contraction: one for isovolumic contractions that locate above that for afterloaded ejecting contractions. Conflicting results to Frank's have been subsequently demonstrated in various species, both within and among preparations, ranging from the whole hearts to single myocytes, showing a single pressure-volume or force-length relation that is independent of the mode of contraction.

The slow force response to stretch: Controversy and contradictions.

When exposed to an abrupt stretch, cardiac muscle exhibits biphasic active force enhancement. The initial, instantaneous, force enhancement is well explained by the Frank-Starling mechanism. However, the cellular mechanisms associated with the second, slower phase remain contentious.

How Accurate Is Inverse Electrocardiographic Mapping? A Systematic In Vivo Evaluation.

Background: Inverse electrocardiographic mapping reconstructs cardiac electrical activity from recorded body surface potentials. This noninvasive technique has been used to identify potential ablation targets. Despite this, there has been little systematic evaluation of its reliability.

Calcium mishandling impairs contraction in right ventricular hypertrophy prior to overt heart failure.

Currently, there are no tailored therapies available for the treatment of right ventricular (RV) hypertrophy, and the cellular mechanisms that underlie the disease are poorly understood. We investigated the cellular changes that occur early in the progression of the disease, when RV hypertrophy is evident, but prior to the onset of heart failure. Intracellular Ca ([Ca]) handling was examined in a rat model of monocrotaline (MCT)-induced pulmonary hypertension and subsequent RV hypertrophy.

Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure.

Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role.

Real-time model-based control of afterload for in vitro cardiac tissue experimentation.

The performance of mechanical work by isolated cardiac muscle samples has typically been studied by subjecting their tissues to an isotonic shortening protocol, which results in "flat-topped" work-loop profiles. In order to better replicate the forces experienced by these tissues in vivo, we have developed a system for imposing a model-based, time-varying, load on isolated cardiac tissue preparations. A model of systemic afterload was developed from the combination of a Windkessel-type model of vascular fluid impedance, and the Laplace law of the heart, and encoded into a hardware-based control system.

The ineluctable constraints of thermodynamics in the aetiology of obesity.

We exploit the detail-independence feature of thermodynamics to examine issues related to the development of obesity. We adopt a 'global' approach consistent with focus on the first law of thermodynamics - namely that the metabolic energy provided by dietary foodstuffs has only three possible fates: the performance of work (be it microscopic or macroscopic), the generation of heat, or storage - primarily in the form of adipose tissue. Quantification of the energy expended, in the form of fat metabolised, during selected endurance events, reveals the inherent limitation of over-reliance on exercise as a primary agent of weight loss.

Experimental and modelling evidence of shortening heat in cardiac muscle.

Key Points: Heat associated with muscle shortening has been repeatedly demonstrated in skeletal muscle, but its existence in cardiac muscle remains contentious after five decades of study. By iterating between experiments and computational modelling, we show compelling evidence for the existence of shortening heat in cardiac muscle and reveal, mechanistically, the source of this excess heat. Our results clarify a long-standing uncertainty in the field of cardiac muscle energetics.

Cardiac muscle energetics: Improved normalisation of heat using optical coherence tomography.

Heat liberated from isolated cardiac muscle has been used to inform us of thermo-mechanical processes that occur during a contraction. However, for comparisons between different samples to be useful, the heat output needs to be normalized to volume. We have implemented an optical coherence tomograph (OCT), together with a flow-through calorimeter, to accurately determine both muscle volume and heat in the same measurement chamber.

Thermodynamic analysis questions claims of improved cardiac efficiency by dietary fish oil.

Studies in the literature describe the ability of dietary supplementation by omega-3 fish oil to increase the pumping efficiency of the left ventricle. Here we attempt to reconcile such studies with our own null results. We undertake a quantitative analysis of the improvement that could be expected theoretically, subject to physiological constraints, by posing the following question: By how much could efficiency be expected to increase if inefficiencies could be eliminated? Our approach utilizes thermodynamic analyses to investigate the contributions, both singly and collectively, of the major components of cardiac energetics to total cardiac efficiency.