Problems concerning the application of concepts of muscle mechanics to the determination of the contractile state of the heart.

THERE HAS BEEN much recent interest by clinical cardiologists in the question of myocardial "contractility" or "contractile state." To the clinician, the quest for a measure of "contractility" or "contractile state" becomes the quest for an early indication of myocardial disease that may be of prognostic value and open up the possibility of preventive measures to forestall serious myocardial disease and failure. Braunwald1 has pointed out that there is a dissociation between the heart's output and its contractile state. In the normal intact dog, an increase in end-diastolic volume (i.e. initial fiber length) increases stroke volume and cardiac output whereas an increase in contractility does not.2 How then can we characterize contractility in the intact heart? The first step is to define it. By contractility or contractile state I mean the following: If one keeps a strip of isolated heart muscle at a constant length, depolariza-tion is either followed by no response (e.g. in aCà + free medium), i.e. there is no contractility, or by tlhe development of force, i.e. there is contractility. Can one quantify the degree of contractility? The amount of force developed increases progressively as the length at which the muscle is held is increased (Frank-Starling mechanism). This phenomenon is here defined as the "length effect." By a change of contractilitv, I mean an altered response which is independent of muscle-fiber length. If this length effect is excluded by holding the muscle at a constant length (isometric) one can now quantify contractility 252 by the amount of isometric force or stress (force/cross-sectional area of muscle) developed. The distinction between changes in cardiac performance due to the Frank-Starling mechanism and those due to changes in contractility are crucial to any study of the subject of contractile state in both isolated heart muscle and intact heart. When heart muscle shortens, one has to consider not only its ability to develop force but also its ability to shorten. These two functions can be expressed by the inverse relation between force and velocity (F-V relation). In skeletal muscle this relationship is a hyperbolic one, the intercept on the velocity axis (velocity at zero force) being called Vii,. and the intercept on the force axis (force at zero velocity), i.e. during isometric contraction, being called Po. The force-velocity curve is length-dependent following the relationship between active force development and muscle length.3 Hoxvever, it has been claimed that in cardiac muscle only P, …