To date, the mechanical loads imposed on isolated cardiac muscle tissue in vitro have been oversimplified. Researchers typically applied loads that are time‐invariant, resulting in either isometric and auxotonic contractions, or flat‐topped (isotonic shortening) work‐loops. These contraction types do not fully capture the dynamic response of contracting tissues adapting to a variable load, such as is experienced by ventricular tissue in vivo. In this study, we have successfully developed a loading system that presents a model‐based, time‐varying, continuously updated, load to cardiac tissue preparations. We combined a Windkessel model of vascular fluid impedance together with Laplace's Law and encoded it in a real‐time hardware‐based force‐length control system. Experiments were carried out on isolated rat left ventricular trabeculae; we directly compare the work‐loops arising from this protocol with those of a typical simplified isotonic shortening work‐loop system. We found that, under body conditions, cardiac trabeculae achieved greater mechanical work output against our new loading system, than with the simplified isotonic work‐loop protocol. We further tested whether loading the tissue with a mechanical impedance defined by “diseased” Windkessel model parameters had an effect on the performance of healthy trabeculae. We found that trabecula shortening decreased when applying the set of Windkessel parameters describing the hypertensive condition, and increased in the hypotensive state. Our implementation of a real‐time model of arterial characteristics provides an improved, physiologically derived, instantly calculated load for use in studying isolated cardiac muscle, and is readily applicable to study various disease conditions.

The uterus provides protection and nourishment (via its blood supply) to a developing fetus, and contracts to deliver the baby at an appropriate time, thereby having a critical contribution to the life of every human. However, despite this vital role, it is an under-investigated organ, and gaps remain in our understanding of how contractions are initiated or coordinated. The uterus is a smooth muscle organ that undergoes variations in its contractile function in response to hormonal fluctuations, the extreme instance of this being during pregnancy and labor. Researchers typically use various approaches to studying this organ, such as experiments on uterine muscle cells, tissue samples, or the intact organ, or the employment of mathematical models to simulate the electrical, mechanical and ionic activity. The complexity exhibited in the coordinated contractions of the uterus remains a challenge to understand, requiring coordinated solutions from different research fields. This review investigates differences in the underlying physiology between human and common animal models utilized in experiments, and the experimental interventions and computational models used to assess uterine function. We look to a future of hybrid experimental interventions and modeling techniques that could be employed to improve the understanding of the mechanisms enabling the healthy function of the uterus.

Preload and afterload dictate the dynamics of the cyclical work-loop contraction that the heart undergoes in vivo. Cellular Ca2+ dynamics drive contraction, but the effects of afterload alone on the Ca2+ transient are inconclusive. No study has investigated whether the putative afterload dependence of the Ca2+ transient is preload dependent. This study is designed to provide the first insight into the Ca2+ handling of cardiac trabeculae undergoing work-loop contractions, with the aim to examine whether the conflicting afterload dependency of the Ca2+ transient can be accounted for by considering preload under isometric and physiological work‑loop contractions. Thus, we subjected ex vivo rat right-ventricular trabeculae, loaded with the fluorescent dye Fura‑2, to work‑loop contractions over a wide range of afterloads at two preloads while measuring stress, length changes, and Ca2+ transients. Work‑loop control was implemented with a real-time Windkessel model to mimic the contraction patterns of the heart in vivo. We extracted a range of metrics from the measured steady‑state twitch stress and Ca2+ transients, including the amplitudes, time courses, rates of rise, and integrals. Results show that parameters of stress were afterload and preload dependent. In contrast, the parameters associated with Ca2+ transients displayed a mixed dependence on afterload and preload. Most notably, its time course was afterload-dependent - an effect augmented at the greater preload. This study reveals that the afterload dependence of cardiac Ca2+ transients is modulated by preload, which brings the study of Ca2+ transients during isometric contractions into question when aiming to understand physiological Ca2+ handling.

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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 model-predicted length change was then imposed on an isolated cardiac trabecula in a work-loop calorimeter, giving rise to force-length work-loops that more closely resemble those experienced by these tissues in vivo.

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Separating the variations in cardiac basal heat rate from variations in active heat rate is necessary to determine cardiac muscle energy consumption accurately during the performance of active work. By developing a model of cardiac muscle basal heat rate, we aimed to investigate changes in basal heat rate when cardiac muscle performs work. Experiments were conducted on 10 isolated rat cardiac trabeculae subjected to both active (work-loops) and quiescent (length-change and velocity) interventions. Muscle force, length and heat output rate were measured simultaneously in a flow-through work-loop calorimeter. Quiescent muscle characteristics were used to parameterize muscle-specific models of change in basal heat rate, thereby to predict dynamic changes in basal heat rate during active work-loop contraction. Our data showed that the quiescent heat characteristics of cardiac muscle varied between samples, displaying dependence on both the extent and the rate of change in muscle length. We found a moderate correlation between muscle dimensions (cross-sectional area and volume) and the length-dependent basal heat parameter (P = 0.0330 and P = 0.0242, respectively), but no correlation with the velocity-dependent parameter.These findings lead us to conclude that the heat output of cardiac muscle at quiescence varies with both the extent and the velocity of shortening, to an extent that is muscle specific, and that this variation must be measured and accounted for in each specimen when assessing active energetics.