Our integrated approach to understanding human cardiac muscle function uses a variety of assays that cover the full range of structural organization, illustrated here. Clinical data, obtained prior to surgery or intravenous catherization, is correlated with mechanical and biochemical data obtained from isolated strips and myofibrils. Single molecule studies conducted by the Warshaw and Lowey/Trybus groups next door complete the integrated examination of disease of the sarcomere. For example, in one recent study of mitral regurgitation (Mulieri et al., Circ. Res. 90, 66-72, 2002), a valvular disease that causes ventricular dilation which can lead to heart failure, we discovered that changes in the kinetics of the motor protein myosin lead not only to a potentially deleterious state of reduced elastance and ejection fraction in the heart, but also a compensatory state of increased economy of tension maintenance and increased resistance to ventricular dilation.

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