Relaxation and diastole of the heart

In the present review, we adopted the viewpoint of the physiologist looking at the global function of the heart, during relaxation and diastole, as an integrated muscle-pump system. We first focused our attention on properties of relaxation and diastole at the subcellular (SR, contractile proteins), cellular, and multicellular scales of cardiac muscle and then at the scale of the ventricle and intact global heart. At each lower scale we derived properties from experimental facts and examined the extent to which these properties could be extrapolated conceptually to the higher scale. From this muscle-pump approach, we learned that a general and fundamental property of relaxation of the heart as a muscle-pump system is load dependence, i.e., the mutually independent behavior of the time patterns of slow force decline and pressure fall and of rapid lengthening and rapid filling. Load dependence is found at all hierarchic scales, irrespective of whether it is examined under strictly isotonic-isometric or isometric-isotonic or auxotonic loading conditions and despite often substantial nonuniformity. Relaxation is governed by the interaction of the loading conditions and the two major determinants of the inactivation process, i.e., Ca2+ reuptake by the SR and the properties of the contractile proteins. Load dependence is the mere mechanical expression of the unequal contribution, during the two phases of relaxation, of these three interacting determinants of relaxation (load, SR, and contractile proteins). During force decline in isolated muscle and pressure fall in the ventricle, the properties of the contractile proteins predominate over load and SR; during muscle lengthening and rapid ventricular filling, load and SR become more important. As the relative importance of the phenomena above is different during pressure fall in comparison to rapid filling, it is not surprising that directional changes in pressure fall may not predict those in filling. We also saw that the overall time pattern of pressure fall in contrast to rapid filling may sometimes be markedly altered, e.g., with simultaneous increases in peak-dP/dt, indicating more rapid early pressure relaxation, and prolonged time constant tau, indicating slower late pressure relaxation, or vice versa. From this muscle-pump approach, it should also be remembered that optimal efficiency of the heart limits the extent to which nonuniformity may exist. At all hierarchic scales, variations in the degree of nonuniformity, however small, constitute an important physiological modulator of performance throughout systole and diastole.(ABSTRACT TRUNCATED AT 400 WORDS)