ABSTRACT
Developing a clinically useful closed-loop drug delivery system can be extremely time consuming and costly. One approach to reducing the time and cost associated with developing closed-loop systems is to reduce the number of animal experiments and perform an extensive set of simulation studies. Through simulations, a closed-loop controller's performance can be evaluated over a complete spectrum of the patient population, including boundary conditions. Simulation studies are repeatable, offering significant advantages in comparing modifications in control algorithms. Finally, simulation studies can be performed in a fraction of the time required for animal studies, at a fraction of the cost. We have developed a simulator, that included a nonlinear pulsatile-flow cardiovascular model, a physiological regulatory mechanism, and the pharmacology of four frequently titrated cardiovascular drugs. This simulator has already been used in the design and evaluation of two closed-loop algorithms-a self-tuning regulator (STR) and a multiple model adaptive controller (MMAC)-for blood pressure control during and after cardiac surgery.
