Mechanisms of cardiac contraction: What roles for preload, afterload and inotropic state in heart failure?

There is evidence that sarcomere length is maximal and changes little during chronic cardiac enlargement, and that the failing heart does not operate on a true descending limb of the Frank-Starling curve. However, increases of ventricular end-diastolic volume over time clearly are important at the geometrical level in maintaining stroke volume. When the preload reserve is fully utilized, afterload mismatch can exist in the steady state to produce operation of the heart on an apparent descending limb of cardiac function, and further afterload mismatch can be produced by pressure loading under these conditions. The treatment of acute experimental heart failure with a mixed vasodilator (nitroprusside) can lead to an increased cardiac output by afterload reduction only when the venous return curve does not shift downward; thus, the threefold larger shift of central blood volume to the periphery in heart failure (compared to normal) counter balances the venodilator action of nitroprusside. Whether or not the inotropic ceiling of failing myocardium can be reached by positive inotropic agents is unclear, but major hemodynamic benefits in heart failure with many potent inotropic drugs are associated with the direct vasodilating properties of these agents. Thus, there appears to be little role for the Frank-Starling mechanism at the sarcomere level, whereas afterload mismatch and its correction are of major importance provided the venous return can be increased. A degree of inotropic reserve also is available, even in the severely failing myocardium, but more research is needed on the potential costs and benefits of marked sustained inotropic stimulation.