Restoring the strength of the heart's contraction relies on the timing of calcium circulation within cardiac myocytes during contraction and relaxation. During relaxation, the calcium that detaches from the contractile proteins is absorbed by the sarcoplasmic reticulum for later release. However, there is a delay of approximately 500 to 800 milliseconds before this calcium becomes available for release in response to the next depolarization. As a result, premature beats are weaker because there isn't enough time during the preceding relaxation for the calcium taken up by the sarcoplasmic reticulum to be released. On the other hand, postextrasystolic beats are significantly stronger than normal because more calcium is released from the sarcoplasmic reticulum due to sympathetic nervous activity.

Enhanced atrial and ventricular contractility is a result of sympathetic nervous activity. The effects of electrical stimulation of the left stellate ganglion on ventricular contraction in an isovolumic left ventricle preparation are illustrated in Figure 18.18. It is worth noting that the duration of systole is shortened and the rate of ventricular relaxation is increased during the early stages of diastole, which aids in ventricular filling. By reducing systole, more time is available for diastole and consequently, ventricular filling.

Norepinephrine released by nerves or circulating catecholamines interact with β-adrenergic receptors on the cardiac cell membranes, as depicted in Figure 18.19. This interaction activates adenylate cyclase, which elevates intracellular levels of cAMP. As a result, protein kinases are activated within the myocardial cells, promoting the phosphorylation of various proteins. Phosphorylation of phospholamban facilitates the uptake of calcium by the sarcoplasmic reticulum, while phosphorylation of troponin I reduces the sensitivity of contractile proteins to calcium. These effects aid in relaxation and reduce end-diastolic pressure. Phosphorylation of specific sarcolemmal proteins also activates calcium channels within the membranes of myocardial cells.

Activation of calcium channels leads to an increase in calcium influx during the action potential plateau, and more calcium is released from the sarcoplasmic reticulum in response to each cardiac excitation. This ultimately enhances the contractile strength of the heart. Figure 18.20 demonstrates the correlation between contractile force in a thin strip of ventricular muscle and the concentration of free calcium in the myoplasm, indicated by the aequorin light signal, as the concentration of isoproterenol (a β-adrenergic agonist) increases.

To fully comprehend the impact of increased sympathetic activity on the heart in intact animals, it is best to consider the families of ventricular function curves. When the frequency of electrical stimulation applied to the left stellate ganglion rises, the ventricular function curves progressively shift to the left. These changes align with those induced by infusions of norepinephrine (see Figure 13.3).
Restitution of the force of contraction depends on the time course of the intracellular circulation of Ca++ in cardiac myocytes during contraction and relaxation. During relaxation, the Ca++ that dissociates from the contractile proteins is taken up by the sarcoplasmic reticulum for subsequent release. However, there is a lag of approximately 500 to 800 msec before this Ca++ is available for release from the sarcoplasmic reticulum in response to the next depolarization. Thus the strength of the premature beat is reduced because the time during the preceding relaxation is insufficient to allow much of the Ca++ taken up by the sarcoplasmic reticulum to become available for release during the premature beat. Conversely, the postextrasystolic beat is considerably stronger than normal because more Ca++ is released from the sarcoplasmic reticulum as a result of the
Sympathetic nervous activity enhances atrial and ventricular contractility. The alterations in ventricular contraction evoked by electrical stimulation of the left stellate ganglion in an isovolumic left ventricle preparation are shown in
Fig.
18.18 . Note that the duration of systole is reduced and the rate of ventricular relaxation is increased during the early phases of diastole; both these effects assist ventricular filling. For any given cardiac cycle length, the abbreviated systole allows more time for diastole and hence for ventricular filling.
). Neurally released norepinephrine or circulating catecholamines interact with β-adrenergic receptors on the cardiac cell membranes (
Fig. 18.19 ). This interaction activates adenylate cyclase, which raises intracellular levels of cAMP (see ). Consequently, protein kinases that promote the phosphorylation of various proteins are activated within the myocardial cells. Phosphorylation of phospholamban facilitates reuptake of Ca++ by the sarcoplasmic reticulum, and phosphorylation of troponin I reduces the sensitivity of contractile proteins to Ca++ . These effects facilitate relaxation and reduce end-diastolic pressure (see ). Phosphorylation of specific sarcolemmal proteins also activates calcium channels in the membranes of myocardial cells.
Activation of calcium channels increases the influx of Ca++ during the action potential plateau, and more Ca++ is released from the sarcoplasmic reticulum in response to each cardiac excitation. The contractile strength of the heart is thereby increased.
Fig. 18.20 shows the correlation between the contractile force in a thin strip of ventricular muscle and the free [Ca++] (indicated by the aequorin light signal) in the myoplasm as the concentration of isoproterenol (a β-adrenergic agonist) is increased (see also
Fig. 13.3
The overall effect of increased cardiac sympathetic activity in intact animals can best be appreciated in terms of 0.1 0.2 0.3 0.4 0.5 0.6 0 0.1 0.2 0.3 0.4 0.5 0.6 Time (sec) •Fig. 18.18 Inanisovolumicleftventriclepreparation,stimulationofcardiacsympatheticnervesevokesasubstantialriseinpeakleftventricularpressureandinthemaximalratesofriseandfallinintraventricularpressure(dP/dt).(FromLevyMN.Unpublishedtracing.) families of ventricular function curves. When the frequency of electrical stimulation applied to the left stellate ganglion increases, the ventricular function curves shift progressively to the left. The changes parallel those produced by infusions of norepinephrine (see