THE CONTRACTILE MECHANISM AS AN APPROACH TO BUILDING LEFT-VENTRICULARPUMP MODELS

Objective: The aim was to construct a model linking a simplified inter pretation of the contractile process at the myofilament level to the m echanical behaviour of the left ventricle to improve the ability of el astic-resistive models to represent the pumping response of the left v entricle. The mechanical model, consisting of an elastic component con nected in series with a contractile component and an elastic component parallel to both the series elastic and contractile components, is ab le to develop pressure by the binding of a structural substance T to a n excitatory substance C, the behaviour of which is a simplification o f miofibrillar Ca2+ kinetics. Methods: Theoretically, the model was va lidated for its ability to reproduce by computer simulation, experimen ts that described the pumping properties of the left ventricle - namel y, elasticity, resistivity, deactivating and positive effect of ejecti on, and the behaviour of intracellular Ca2+. Experimentally, the model was tested to fit intraventricular pressure (P(t)) and volume (V(t)) of single ejective beats in nine open chest dogs fitted with a pressur e microtransducer to measure intraventricular P(t) and an aortic flowp robe to measure ventricular outflow and calculate V(t). Parameters wer e estimated up to maximum negative dP/dt adjusting P(t) or V(t) data o f the ejective beats, and the goodness of the fit was evaluated throug h the root mean square error normalised with respect to the correspond ing mean P(t) or V(t) in the fitting interval (NE). Results: Descripti ve validation of the model showed that the mean NE for the ejective P( t) fit was 0.03(SD 0.005) and for the V(t) fit 0.014(0.003). Predictiv e validation of P(t) and V(t) data of beats with partial occlusion of the aorta was performed up to end ejection, with parameters estimated from the P(t) or V(t) fit of the preceding ejective beat. Results gave a mean NE equal to 0.05(0.02) for predicted P(t) and 0.02(0.007) for predicted V(t)), from either source of estimated parameters. Explanati ve validation showed that all the estimated parameters were in the sam e range used in simulation and that derived indexes [isovolumic maximu m pressure (P(max))=166(13) mm Hg, time to maximum pressure (TP(max)=0 .186(0.012) s and the slope of the end systolic pressure volume relati on (E(max)=5.45(1.5) mm Hg.ml-1] were within reported experimental val ues. Finally, the model responded to increased inotropic state [dobuta mine (5-35 mug.kg-1.min-1)] causing the estimated P(max) and E(max) to increase by 33% and 25%, respectively, and TP(max) to decrease by 10% . Conclusion: This model represented an improvement over previous pump models because (1) the model was able to represent behaviours other t han purely elastic-resistive ones, such as the deactivation and positi ve effect of ejection; (2) left ventricular properties were the respon se of model behaviour and not constitutive elements of its structure; and (3) it adequately fulfilled model validation procedures.