In 2001, James Norton went through the physiology literature looking at how preload was defined. He found roughly thirty different definitions. Preload had been used to mean myocardial fibre tension, fibre stretch, fibre length, end-diastolic volume, end-diastolic pressure and several other things besides.
Twenty-five years later, we still move between these meanings almost without noticing.
At the bedside, “preload” may mean CVP. It may mean ventricular filling pressure, chamber volume, venous return or circulating volume. Sometimes it simply means giving fluid.
These are not interchangeable measures of the same thing.
A pressure is not a volume. A chamber volume is not myocardial stretch. Venous return is not preload. And fluid administration is an intervention, not a myocardial state.
Still, we routinely join them together into one of the most familiar stories in cardiovascular physiology:
Give fluid → increase preload → move up the Frank–Starling curve → increase stroke volume → increase cardiac output.
Look at that sequence closely and some awkward questions appear.
Why can a profoundly hypovolaemic heart contract so violently when its ventricle is almost empty?
Why can an empty beating heart on bypass continue to contract at all if stretch is supposed to be what makes the heart pump harder?
Why can increasing cardiac stimulation fail to increase flow in one circulation, while altering the vascular side of the same circuit suddenly produces a large rise in cardiac output without any further change in heart rate or contractility?
Why can a ventricle remain small and hyperdynamic even when cardiac output is very high?
And if Frank–Starling really is the mechanism that converts “more preload” into more cardiac output, what exactly is it doing when the heart already has more than enough contractile capability for the flow being delivered to it?
At the other end of the spectrum, very small increases in cardiac volume can eventually produce large increases in filling pressure. What determines when that happens? How much additional volume can the heart accommodate before pressure rises sharply? And what is Frank–Starling doing as inflow and outflow begin to mismatch?
Robert Anderson was thinking about some of these problems decades ago when he described the heart as having volume reserve and energy reserve. Those ideas never became part of the usual clinical vocabulary, but they provide a useful way of putting preload, Frank–Starling, filling pressure and cardiac output back into the same physiological picture.
First, though, we need to decide what preload actually is.
What is preload?
At its most fundamental, preload describes the mechanical state of the myocardium at the end of filling, immediately before contraction. At the level of the muscle fibre, that means things such as sarcomere length and wall stress. At the level of the whole ventricle, end-diastolic volume is a useful approximation.
Pressure is different.
Right and left atrial pressures are simply that - measurements of filling pressure, not direct measurements of ventricular volume or myocardial stretch. The relationship between pressure and volume depends on the properties of the ventricle, its geometry, its current filling state, the pericardium, intrathoracic pressure, ventricular interaction and other external constraints.
A stiff ventricle may reach a high filling pressure while containing relatively little blood. A compliant ventricle may contain considerably more blood at a lower pressure.
The same filling pressure can therefore be associated with very different end-diastolic volumes, and the same end-diastolic volume can occur at different filling pressures.
This is the first problem with using CVP or RAP as a synonym for preload. Filling pressure tells us something about the pressure associated with filling. It does not uniquely tell us how full the heart is, how stretched the myocardium is or how much additional blood it can accept.
Nor does low preload mean that the heart cannot contract forcefully.
An empty heart can still contract violently
Anyone who has looked after a profoundly hypovolaemic or vasodilated patient has seen the small hyperdynamic ventricle. The cavity may be tiny. Sympathetic activation is intense. The heart rate is high. The ventricular walls move vigorously.
There is very little blood in the chamber, but there is nothing weak about the contraction.
The same point becomes even clearer on cardiopulmonary bypass. Even with the heart emptied, the myocardium can continue to contract forcefully.
Myocardial contraction does not require the ventricle first to be filled or stretched. It is initiated by electrical activation, calcium cycling and cross-bridge interaction. Sympathetic stimulation can increase that activation further.
Stretch does something different. Through length-dependent activation, it modifies the mechanical response of myocardium that is already active.
This distinction is easily lost when Frank–Starling is described as though filling first “switches on” ventricular performance.
It does not.
Activation makes the myocardium contract. Preload modifies what that activated myocardium does.
That becomes important when the heart has far more mechanical capability than the amount of blood being delivered to it allows it to express.