This chapter explores the adaptive control of cardiac function by the loading conditions and relates the observed phenomena to our theory of the sarcomeric control of contraction. Our theory includes two feedback mechanisms: cooperativity-regulated cross-bridge recruitment and energy consumption, and mechanical feedback that determines the interplay between the external work and the force-time integral. The latter also suggests that cardiac efficiency is load independent. This paper explores the regulation of cardiac function by loading conditions, and the role of afterload in adult sheep in situ (n=8). Different afterloads were imposed by partial aortic occlusions. Transient inferior vena cava occlusions (IVCOs) were pre-formed at each steady afterload. A novel, highly linear relationship was found between the external work and pressure-time integral during each transient IVCO at constant afterload. Of interest, the slope of this relationship was afterload-dependent also during fast transient changes in the afterload. These observations are congruent with the suggested adaptive sarcomeric control of contraction, and may provide a powerful tool for quantifying cardiac function.