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Control of Cardiac Output and Starling’s Law of The Heart


Control of Cardiac Output and Starling’s Law of The Heart
Cardiac output (CO) is determined by the heart rate and stroke volume (SV): CO = heart rate × SV. SV is influenced by the filling pressure (preload), cardiac muscle force, and the pressure against which the heart has to pump (afterload). Both the heart rate and force are modulated by the autonomic nervous system (ANS) (Fig. 20a). The heart and vasculature form a closed system, so except for transient perturbations venous return must equal CO.


Control Of Cardiac Output And Starling’s Law Of The Heart

Filling pressure and Starling’s law
The right ventricular end-diastolic pressure (EDP) is dependent on central venous pressure (CVP); left ventricular EDP is dependent on pulmonary venous pressure. EDP and the compliance of the ventricle (how easy it is to inflate) determine the end-diastolic volume (EDV). As EDP (and so EDV) increases, the force of systolic contraction and thus SV also increases. This is called the Frank–Starling relationship, and the graph relating SV to EDP is called a ventricular function curve (Fig. 20b). The force of contraction is related to the degree of stretch of cardiac muscle, and Starling’s law of the heart states: ‘The energy released during contraction depends on the initial fibre length’. As muscle is stretched, more myosin cross-bridges can form, increasing force (sliding filament theory; Chapter 12). However, cardiac muscle has a much steeper relationship between stretch and force than skeletal muscle, because stretch also increases the Ca2+ sensitivity of troponin (Chapter 12), so more force is generated for the same intracellular Ca2+. The ventricular function curve is therefore steep, and small changes in EDP lead to large increases in SV.

Importance of Starling’s law
The most important consequence of Starling’s law is that SV in the left and right ventricles is matched. If, for example, right ventricular SV increases, the amount of blood in the lungs and thus pulmonary vascular pressure will also increase. As the latter determines left ventricular EDP, left ventricular SV increases due to Starling’s law until it again matches that of the right ventricle, when input to and output from the lungs equalize and the pressure stops rising. This represents a rightward shift along the function curve (Fig. 20b). Starling’s law thus explains how an increase in CVP, which is only perceived by the right ventricle, can increase CO. It also explains why an increase in afterload (e.g. hypertension) may have little effect on CO. It should be intuitive that an increase in afterload will reduce SV if cardiac force is not increased. However, this means more blood is left in the left ventricle after systole, and also that the outputs of the two ventricles no longer match. As a result, blood accumulates on the venous side and filling pressure rises. Cardiac force therefore increases according to Starling’s law until it overcomes the increased afterload and, after a few beats, CO is restored at the expense of an increased EDP.

Autonomic nervous system
The autonomic nervous system (ANS) provides an important extrinsic influence on CO. Sympathetic stimulation increases heart rate whereas parasympathetic decreases it; sympathetic stimulation also increases cardiac muscle force without a change in stretch (or EDV) (i.e. it increases contractility; Chapter 19). The ventricular function curve therefore shifts upwards (Fig. 20b). By definition, Starling’s law does not increase contractility.
Activation of sympathetic nerves also induces arterial and venous vasoconstriction (Chapter 22). An often overlooked point is that these differ in effect. Arterial vasoconstriction increases total peripheral resistance (TPR) and impedes blood flow. However, unlike arteries, veins are highly compliant (stretch easily), and contain 70% of blood  volume.  Venoconstriction  reduces  the  compliance  of  veins and hence their capacity (amount of blood they contain), and there- fore has the same effect as increasing blood volume, i.e. CVP increases. Venoconstriction does not significantly impede flow because venous resistance is very low compared to TPR. Sympathetic stimulation therefore increases CO by increasing heart rate, contractility and CVP.
Postural hypotension. On standing from a prone position, gravity causes blood to pool in the legs and CVP falls. This in turn causes a fall in CO (due to Starling’s law) and thus a fall in blood pressure. This postural hypotension is normally rapidly corrected by the baroreceptor reflex (Chapter 22), which causes venoconstriction (partially restoring CVP) and an increase in heart rate and contractility, so restoring CO and blood pressure. Even in healthy people it occasionally causes a temporary  blackout  (fainting  or  syncope)  due to reduced cerebral perfusion. Reduction of  ANS  function  with age accounts for a greater likelihood of postural hypotension as we get older.

Venous return and vascular function curves
Blood flow is driven by the arterial–venous pressure difference, so venous return will be impeded by a rise in CVP (Fig. 20c). This is at first glance inconsistent with Starling’s law if CO must equal venous return. However, CVP is only altered by changes in blood volume or its distribution (e.g. venoconstriction), and these also alter the relation- ship between CVP and venous return (the vascular function curve; Fig. 20c). This figure indicates that venous return is maximum when CVP is zero (the flattening of the curve reflects venous collapse at negative pressures). Conversely, venous return will be zero if the heart stops, when pressures equalize throughout the vascular system to a mean circulatory pressure (PMC); by definition CVP will equal PMC at this point. PMC is dependent on the vascular volume and compliance, and thus primarily on venous status (see above). Raising blood volume or venoconstriction therefore increases PMC and causes a parallel shift of the vascular function curve; the reverse occurs in blood loss. In contrast, arterial vasoconstriction has insignificant effects on PMC because the volume of resistance arteries is small; it does however reduce venous return due to the increase in TPR (see above). The net effect is therefore to reduce the slope of the curve, whilst a reduction in TPR increases it.
Guyton’s analysis combines vascular and cardiac function curves into one graph (Fig. 20d). The only point where CO and venous return are equal is the intersection of the curves (A); this is thus the operating point. If blood volume is now increased, the shift in the vascular function curve leads to a new operating point (B) where both CO and CVP are increased; blood loss does the opposite (C). In exercise, a more complex example, sympathetic stimulation causes both increased cardiac contractility and venoconstriction, but TPR falls due to vasodilation in active muscle. Thus both cardiac and vascular function curves shift up, but because of the fall in TPR the latter has a steeper slope (see above). The new operating point (D) shows that in exercise CO can be greatly increased with only minor changes in CVP.