Kinetics of restitution of left ventricular relaxation.

Abstract

Although the kinetics of cardiac systolic force restitution have been well described, the restitution kinetics of left ventricular relaxation have not been examined. animals2'3 as well as in isolated hearts4-6 and isolated muscle preparations.7-10Weir and Yue10 have shown that the time constants of mechanical restitution and postextrasystolic potentiation are very similar and that contractile response has a linear correlation with intracellular Ca'+ concentration. Their studies with ryanodine, an inhibitor of the sarcoplasmic reticulum (SR) Ca2t release channel, have defined an essential role for the SR in the force-interval relation. These investigators concluded that the relation is a physiological expression of the availability of intracellular Ca2 , which is dependent on the SR. A phenomenological model of Ca2' flux among the SR, myoplasm, and extracellular space has been proposed to describe the kinetics of the force-interval relation.6'10Despite the large body of work performed delineating cardiac systolic restitution, very little has been done to define the pattern by which the heart's ability to relax rapidly returns after a stimulus, a phenomenon we term relaxation restitution. Relaxation, like myocardial contraction, is an energy-requiring process. Myocardial crossbridge separation and sarcomere force decay are dependent on active Ca21 uptake by the SR and resultant dissociation of Ca2' from troponin C. Although sarcolemmal Na+-Ca21 exchange participates in determining intracellular Ca2' levels, it is a low-affinity transport system and probably does not play a major role during isovolumic relaxation (see Reference 11 for review).

Influence of sarcoplasmic reticulum calcium loading on mechanical and relaxation restitution

“…In support of this concept, cross signaling between Ca 2ϩ channels and the ryanodine receptor have recently been demonstrated with confocal microscopy (6). Recovery of relaxation (ϪdP/dt max ) also occurs as a monoexponential function and can be described by a TC (23,24). Although relaxation restitution is most rigorously described by two concatenated monoexponentials, we examined only the first, rapid phase of restitution, because ϪdP/dt max was not measured in ESI beyond the basic cycle length.…”

“…Relaxation restitution was calculated by normalizing peak ϪdP/dt of the extrastimulus beat to the peak ϪdP/dt of the basic cycle length and fitting the relation between 1/normalized dP/dt and the ESI to a monoexponential function (23,24).…”

“…As the extrastimulus interval increased from the first appearance of mechanical activity to the basic cycle length, there was an exponential increase in ϪdP/dt max (and thus a decrease in the reciprocal, 1/normalized ϪdP/dt max ). The TC of the exponential decay was used to characterize relaxation restitution (23,24).…”

“…Relaxation restitution represents the increase in left ventricular (LV) relaxation rate associated with progressively longer ESI. Prabhu and Freeman (23,24) used a compartmental model with similar kinetic-related assumptions and suggested that restitution of relaxation reflects SR Ca 2ϩ uptake capacity. However, data regarding relaxation restitution have not been studied in detail, and parameters of mechanical restitution are conflicting, in part because of differences in preparation, species, and methodology (1,23,31,32).…”

Limitations of R‐average as an index of left ventricular isovolumic relaxation

“…Recently, Freeman and coworkers (Prabhu & Freeman, 1992, Freeman et al, 1993) introduced a new isovolumic relaxation parameter, termed the R-average. The Raverage was defined as the average pressure fall during the isovolumic relaxation period, i.e.…”