Both the increased magnitude and the slowed inactivation of iCa lead to greater Ca++ influx into the myocyte during later depolarizations compared to the first depolarization, resulting in stronger contraction. Transient changes in the intervals between beats also significantly impact the strength of contraction. When the left ventricle contracts prematurely (beat A), the premature contraction itself is weak, while the postextrasystolic contraction (beat B) after the compensatory pause is very strong. This response is partly dependent on the Frank-Starling mechanism in the intact circulatory system. Insufficient time for ventricular filling just before the premature beat leads to a weak premature contraction. Subsequently, the exaggerated degree of filling associated with the long compensatory pause contributes to the vigorous postextrasystolic contraction. The strength of the premature beat is directly related to its degree of prematurity, with earlier premature beats resulting in weaker force of contraction. The curve representing the strength of contraction of a premature beat in relation to the coupling interval is called a mechanical restitution curve. An example of such a curve is shown in Figure 18.17, which was obtained from an isolated ventricular muscle preparation. In this preparation, the premature ventricular systolic contraction (beat A) is typically weak, while the postextrasystolic contraction (beat B) is characteristically strong. The enhanced contractility may diminish over a few contractions (e.g., beat C). The restitution curve demonstrates the force generated during premature contractions based on different intervals between beats. In addition to intrinsic mechanisms, extrinsic factors play a role in regulating myocardial performance. These extrinsic regulatory mechanisms, including nervous and chemical components, can often have a greater influence on the heart compared to intrinsic mechanisms.
Fig. 18.15 ). Both the increased magnitude and the slowed inactivation of iCa result in greater Ca++ influx into the myocyte during the later depolarizations than during the first depolarization. This greater Ca++ influx strengthens contraction.
Transient changes in the intervals between beats also profoundly affect the strength of contraction. When the left ventricle contracts prematurely (
Fig. 18.16 , beat A), the premature contraction (extrasystole) itself is weak, whereas contraction B (postextrasystolic contraction) after the compensatory pause is very strong. In the intact circulatory system, this response depends partly on the Frank-Starling mechanism. Inadequate time for ventricular filling just before the premature beat results in the weak premature contraction. Subsequently, the exaggerated degree of filling associated with the long compensatory pause (see
Fig.
18.16 , beat B) contributes to the vigorous postextrasystolic contraction.
The weakness of the premature beat is directly related to its degree of prematurity: The earlier the premature beat, the weaker its force of contraction. The curve that represents strength of contraction of a premature beat in relation to the coupling interval is called a mechanical restitution curve.
Fig. 18.17 shows the restitution curve obtained when the coupling intervals of test beats were isolated in an isolated ventricular muscle preparation.
0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 Time (sec) •Fig. 18.16 Inanisovolumicleftventriclepreparation,aprematureventricularsystoliccontraction(beat
A)istypicallyweak,whereasthepostextrasystoliccontraction(beatB)ischaracteristicallystrong,andtheenhancedcontractilitymaydiminishoverafewcontractions(e.g.,beatC).(FromLevyMN.Unpublishedtracing.) 100 80 60 40 20 0 0 0.2 0.4 0.6 0.8 1.0 Test beat interval (sec) Test beat force (% of max) relatively large amount of Ca++ taken up by it during the time that had elapsed from the end of the last regular beat until the beginning of the postextrasystolic beat.
Extrinsic Regulation of Myocardial Performance
Although a completely isolated heart can adapt well to changes in preload and afterload, various extrinsic factors also influence the heart in an individual. Often, these extrinsic regulatory mechanisms may overwhelm the intrinsic mechanisms. The extrinsic regulatory factors may be subdivided into nervous and chemical components.
•Fig. 18.17 Force Generated During Premature Contractions in an Isolated Ventricular Muscle Preparation. Themusclewasstimulatedtocontractoncepersecond.Periodically,themusclewasstimulatedprematurely.Thescalealongthex-axisdenotesthetimebetweenthedrivenandtheprematurebeat.Thescalealongthey-axisdenotestheratioofthecontractileforceoftheprematurebeattothatofthedrivenbeat.(ModifiedfromSeedWA,WalkerJM.Cardiovasc Res. 1988;22:303.)