Triple control of relaxation: implications in cardiac disease.

EARLY DETECTION of impaired relaxation has been emphasized recently for the evaluation of global and regional ventricular function in patients with heart disease. Although early relaxation abnormalities have been found in various cardiac diseases, the underlying mechanisms are not as yet fully understood. Given the recent progress in our understanding of relaxation of the heart,' these mechanisms can now be discerned more easily. We will first summarize our present knowledge of relaxation of cardiac muscle or, more specifically, how relaxation is controlled by the three following interacting determinants: (1) load, (2) (in)-activation, and (3) nonuniform distribution of load and (in)activation in space and in time. Then, the concept of triple control will be extended to that of the intact heart in situ as a pump. We will also review how multiple factors, acting either alone or in concert depending on the nature of the disease, underlie early relaxation abnormalities in patients with heart disease. Finally, measurements of ventricular relaxation will be critically discussed in view of these newer concepts. Mechanical aspects of relaxation of isolated cardiac muscle Performance of the heart during the contraction phase, both as a muscle and as a muscle-pump system, is regulated through two distinct but interrelated functions , namely heterometric autoregulation or control by changes in load (volume and/or pressure) and ho-meometric autoregulation or control by changes in contractility. Although regulation of performance by changes in load is conceptually related to heterometric autoregulation and regulation of performance by changes in contractility to homeometric autoregula-tion, these concepts are not quite identical. By the same token, although changes in contractility are usu-190 ally believed to be the mechanical expression of changes in activation, the concepts of contractility and activation should not be used interchangeably. Given the complexity of the intact heart, one should also take into account some degree of nonuniform distribution of the former two mechanisms as a third important physiologic determinant of performance. We have recently learned that a similar triple control mechanism also operates during the relaxation phase. Relaxation of the heart, both as a muscle and muscle-pump system, is governed by the continuous interplay of the sensitivity of the contractile system to the prevailing load and the dissipating activation (inactiva-tion). ' For a given set of loading conditions, relaxation can be modulated by subtle alterations of the load dependence due to changes in the underlying dissipa-tion of activation. Alternatively, for a given load …