Mechanical loading of isolated cardiac muscle with a real-time computed Windkessel model of the vasculature impedance.

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.
(© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)