Shortening deactivation of cardiac muscle: physiological mechanisms and clinical implications

PHYSIOLOGICAL MECHANISM: A rapid change of length applied during isometric contraction of skeletal or cardiac muscle may result in redeveloped tension less than appropriate for the new length because of "deactivation" of the contractile system. The amount of shortening deactivation is directly related to both the time during the contraction when the length change occurs and to the extent of muscle shortening. If the muscle is permitted to shorten early in the contraction, the redeveloped tension will be appropriate to the new length as predicted from the classic Frank-Starling relationship. However, the same length change, which is imposed later in the contraction, results in a redeveloped tension that is less than predicted. Furthermore, a greater change in length results in less tension being redeveloped than if a smaller length decrement is applied at the same time during the contraction. It has been demonstrated that the reduced tension during active muscle shortening is associated with reduced affinity of troponin C for Ca2+. The free Ca2+ is then picked up by the SR, with less Ca2+ available for tension development until the subsequent contraction.

Although the clinical significance of shortening deactivation remains speculative, it seems likely that in the intact heart deactivation would affect myocardial O2 consumption. The decreased efficiency with which the heart maintains a given stroke work against a high afterload might be related to the lesser degree of fiber shortening and, therefore, less shortening deactivation. Conversely, it is well-known that the same level of stroke work accomplished by an increase in end-diastolic volume requires much less O2. This may be related, at least in part, to the greater degree of shortening with an accompanying increase in deactivation under the latter conditions. For example, in congestive heart failure where ejection fraction and fiber shortening are minimal, the maintenance of the longer fiber lengths could significantly increase the MVO2. Ford has suggested that the deactivating effect of shortening produced by afterload reduction would limit energy expenditure, therefore, exerting a favorable effect on the failing myocardium. It would also seem that an inotropic agent that increased shortening deactivation might compensate for the increased MVO2 caused by the inotrope and have a favorable effect on cardiac work. From most of the studies we have reviewed, it appears likely that shortening deactivation acts as a physiological "feedback" mechanism that affects afterload and in turn, myocardial oxygen consumption. Pathological situations such as acidosis and ischemia have been associated with reduced myofilament Ca2+ sensitivity or affinity and depressed cardiac contractility. Is it then possible that interventions that increase Ca2+ sensitivity might favorably alter ventricular pressure-volume relations during ejection and improve myocardial function by reducing the magnitude of shortening deactivation? Whatever the mechanism and clinical significance, future investigations will help to define the role of shortening deactivation in modifying ventricular function.