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.
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.
