Mechanical pathophysiology of some heart diseases: a theoretical model study

Sarcomere dynamics are related to the global left ventricular (LV) function in some representative pathological states, by using a theoretical model which combines sarcomere function, LV fibrous structure and geometry with the haemodynamic loading conditions. The analysis shows that pressure (concentric) hypertrophy due to hypertension or aortic stenosis is associated with an increase of the normal endocardial-to-epicardial gradient(s) of oxygen demand, which may be one of the causes for the development of endocardial fibrosis. The analysis also indicates that sarcomere shortening is relatively normal in compensated volume (eccentric) hypertrophy. Mitral stenosis demonstrates a case of decreased LV function, secondary to a chronic decrease in LV end diastolic volume, with sarcomeres that operate at their lowest length range. Conversely, the sarcomere function is depressed in cardiomyopathy; the heart's pumping function is maintained by appropriate adjustment mechanisms. However, the sarcomeres show minimal shortening and function at their highest length range with low (or zero) functional reserve. The study thus provides a quantitative tool that relates global LV function to local sarcomere dynamics in various pathological states.