Callum M. Johnston

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

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.

Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.

Long‐term systemic arterial hypertension, and its associated compensatory response of left‐ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left‐ventricular trabeculae from SHR‐F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR‐NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR‐F differed little from that of the SHR‐NF, both SHR groups performed less stress‐length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca2+ cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension‐induced left‐ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced.

Muscle heat: a window into the thermodynamics of a molecular machine

The contraction of muscle is characterized by the development of force and movement (mechanics) together with the generation of heat (metabolism). Heat represents that component of the enthalpy of ATP hydrolysis that is not captured by the microscopic machinery of the cell for the performance of work. It arises from two conceptually and temporally distinct sources: initial metabolism and recovery metabolism. Initial metabolism comprises the hydrolysis of ATP and its rapid regeneration by hydrolysis of phosphocreatine (PCr) in the processes underlying excitation-contraction coupling and subsequent cross-bridge cycling and sliding of the contractile filaments. Recovery metabolism describes those process, both aerobic (mitochondrial) and anaerobic (cytoplasmic), that produce ATP, thereby allowing the regeneration of PCr from its hydrolysis products. An equivalent partitioning of muscle heat production is often invoked by muscle physiologists. In this formulation, total enthalpy expenditure is separated into external mechanical work (W) and heat (Q). Heat is again partitioned into three conceptually distinct components: basal, activation, and force dependent. In the following mini-review, we trace the development of these ideas in parallel with the development of measurement techniques for separating the various thermal components.

Vapor pressure thermometry at room temperature

Many calorimetric sensing applications, such as measurement of heat exchange in chemical reactions or of the heat production of biological specimens, require high-resolution temperature sensors suitable for use at or near room temperature. We have developed a thermometer that measures changes in the vapor pressure of a volatile substance to infer the temperature of its liquid phase. Our prototype sensor provided a noise-equivalent-temperature resolution of 16 μK over a 1 Hz bandwidth — an order of magnitude improvement over previous vapor-pressure thermometers. The thermometer design enables temperature-resolution that has the potential to be extended to the microkelvin range, and imposes minimal thermal load on the heat source. Furthermore, the sensing element responsible for transduction of temperature changes into movement is inexpensive, enabling the possibility of disposable transducing elements in a sensor system. While this thermometer demonstrates the feasibility of the modality for high-resolution measurements of temperature change, without further advances in methodology current construction techniques limit the reproducibility between sensors, which may constrain the wide applicability of the sensor system.

A vapor pressure thermometer for use in muscle microcalorimetry

Measurement of the energy consumption of isolated cardiac trabeculae requires highly sensitive temperature sensors. In this paper we describe and characterize an initial prototype of a vapor pressure thermometer being designed and built for application to muscle microcalorimetry. The device exploits the change in vapor pressure with temperature of a solvent and the change in pressure with volume of a gas. The sensor achieves a sensitivity of 86 μm/K and a resolution of 3.6 μK. Predictions from a finite element model of the expected displacement compare favorably with the tests performed.