"First, a simulation environment of the sarcomere will be developed by using lumped parameter models. This model will be incorporated into existing models of the cardiac contraction to eventually build a multi-scale model of the cardiovascular loop. At a later stage, this model will be coupled to local 3D models of cardiac devices. The study will focus on one specific application in cardiovascular engineering: valve closure force. Whilst forces of closure of prosthetic heart valves are an important characteristic with respect to the design, they are very difficult to quantify. Also, cavitation might be a problem, as could lead to catastrophic failure or blood damage. Closure lasts for only about 35 ms, and there are no adequate models that can predict or quantify the effect of local/cellular events of chemical, biochemical or mechano-electrical nature at the ventricular level on the closure forces. For potentially high-risk patients is possible that pharmacokinetical intervention may reduce the cavitation potential of the valve and risk of fracture. We propose to develop the first coherent multi-scale model of the system taking into account the cellular mechanisms of cardiac contraction, with feedback between electrochemical events in the vessel wall and detail haemodynamic characteristics of the flow"