Effect of early diastolic loading on myocardial relaxation in the intact canine left ventricle

Early transmitral flow (MiF) patterns depend strongly on the rate of fall of measured left ventricular pressure (Pm) determined by both the active decay of pressure (Pa) due to myocardial relaxation and the increase in pressure due to stretch of passive elements during filling (Pp). This study was designed to uncouple passive forces from deactivation in order to reveal the instantaneous rate and duration of myocardial relaxation. We assumed a parallel combination of passive and active elements: Pm(t,V) = Pa(t) + Pp(V), with no constraints on the form of Pa(t), where t is time and V is ventricular volume. Pp(V) was determined by a retrospective analysis of data obtained in 11 anesthetized dogs instrumented for volume clamping with a remote-controlled mitral valve, with left atrial and left ventricular micromanometers, and with an electromagnetic probe to measure MiF. The passive pressure-volume relation (both positive and negative portions) was determined by clamping at end-systolic volume or after various filling volumes, and fit to logarithmic functions. Pp(t) was then calculated from Pp(V) and V(t) (integral of MiF). Time to end relaxation (Ter) was defined as time when Pa = 0. During isovolumic relaxation, when dPp/dt = 0, dPm/dt is equal to the relaxation rate, dPa/dt. In completely isovolumic relaxations, asymptote P infinity = -7 +/- 6 mm Hg (thus, Pa is 7 mm Hg greater than Pm) and Ter = 40 +/- 15 msec, compared with 175 +/- 53 msec during normal filling. In high versus low inotropic state, Pa at the beginning of filling was greater (18.1 +/- 6.1 vs. 12.2 +/- 3.9 mm Hg), and Ter was shorter (170 +/- 42 vs. 228 +/- 43 msec). Active pressure Pa(t) during filling is not an exponential function, and at any time, it was always greater after filling than in nonfilling beats, which indicates an increase in the relaxation duration. We conclude that myocardial relaxation is modulated by filling, which slows its rate and increases its duration, and is therefore a function of both ventricular volume and time. Such a mechanism may have an important role in regulating the diastolic pressure-volume relation.