Analysis of the effects of changes in rate and rhythm upon myocardial contractility.

During periods of quiescence the contractility of heart muiuscle approaches asymptotically a state characterized by the rested-state contraction. Activation of the muscle produces two temporary changes with opposing effects upon contractility. One tends to increase the strength of subsequent beats; it is responsible for the positive inotropic effect of activation (PIEA). The other tends to decrease the strength of following contractions and is manifest as the negative inotropic effect of activation (NIEA). The strength of a beat occurring at any given monuent is equal to that of the rested-state contraction, plus the cumulated PIEA, minus the cumulated NIEA. Changes in the absolute amounts of the PIEA and the NIEA account for the various changes in the strength of contraction that result from changes in the rate or rhythm of the heart. Both effects are operative in all homeothermic species investigated, but there are marked species differences in the relative prominence of the two and in the frequency ranges over which they are important. The intensity of the states responsible for the positive and negative inotropic effects of activation can be measured over a wide range by the resulting alterations in the strength of contraction. Changes in the intensity of the two states result from every beat whatever the frequency of contraction. Both states are capable of cumulation; the extent of cumulation depends on their respective rates of production and decay. Methods for the quantitative determination of these rates are described. The following observations account for the marked differences in the cumulation of the two effects at various frequencies of contraction: 1) each beat has a relatively small positive inotropic effect of activation, and the effect disappears slowly and exponentially; 2) each beat has a larger negative inotropic effect of activation which disappears rapidly in the period immediately following the beat, and then more slowly and exponentially; 3) the amounts of the PIEA and the NIEA produced per beat and the characteristics of the PIEA and NIEA decay curves are not necessarily independent of the interval between contractions. The positive and negative inotropic effects of activation reflect primarily changes in the force-velocity relationship rather than in the duration of the active state of the muscle.