Ventricular Pressure-Volume Relationship: Preload, Afterload, Stroke Volume, Wall Stress & Frank-Starling’s law
Ventricular Pressure-Volume Relationship
Left ventricular pressure-volume relationship can be described by a loop diagram with volume depicted on the x-axis and left ventricular pressure on the y-axis. If left ventricular pressure and volume are measured continuously during a single cardiac cycle, the loop diagram shown in Figure 1 is obtained.
In Figure 1 we begin in diastole, when the mitral valve opens. When the mitral valve opens, blood flows into the left ventricle. This results in a rapid increase in left ventricular volume, but only a small increase in left ventricular pressure. This is explained by the fact that the left ventricle is capable of relaxing and expanding rapidly during diastole. The term complianceis used to describe the ability of the left ventricle to relax during diastole. Compliance is fundamental to diastolic function. High compliance is desireable and means that the ventricle is capable of filling rapidly while operating at low end-diastolic pressure.
EDV (End Diastolic Volume) denotes the volume in the left ventricle, just before contraction commences. Left ventricular pressure increases when the contracting starts, and when left ventricular pressure exceeds left atrial pressure, the mitral valve closes. Upon closing of the mitral valve, left ventricular pressure increases rapidly while both the aortic valve and the mitral valve are closed. This phase is called isovolumetric contraction (IVC; Figures 1 and 2).
When left ventricular pressure exceeds diastolic pressure in the aorta, the aortic valve opens and blood is ejected into the aorta. Left ventricular volume decreases as the ventricle contracts and pumps blood into the aorta. After the maximum pressure is reached, the ventricle relaxes, which results in diminished left ventricular pressure. The aortic valve closes when aortic pressure exceeds left ventricular pressure.
ESV (End Systolic Volume) is defined as left ventricular volume at the closure of the aortic valve. Upon aortic valve closure, the ventricle relaxes and pressure drops rapidly, without any significant changes in volume. This phase is referred to as isovolumetric relaxation (IVR; Figures 1 and 2). When the ventricular pressure is less than left atrial pressure, the mitral valve opens and the cycle is repeated.
Stroke volume (SV) and stroke work (SW)
Stroke volume (SV) is defined as the difference between ESV and EDV, which is equivalent to the width of the loop in Figure 1. The area within the loop is the stroke work (SW), which is discussed below.
The pressure-volume loop in Figure 1 can be moved along the black lines called EDPVR and ESPVR. EDPVR (End-Diastolic Pressure-Volume Relationship) shows the relationship between ESV and left ventricular volume. The EDPVR curve shows that the left ventricle can withstand large pressure increases but at a certain threshold, pressure rises rapidly with further increases in volume. This is explained by the existence of an upper limit for ventricular compliance. The greater the left ventricular compliance, the less steep the slope of the EDPVR curve, and vice versa.
ESPVR (End-Systolic Pressure-Volume Relationship) shows how maximum pressure varies with volume. The smaller the EDV, the lower the maximum generated pressure, and the smaller the stroke volume. Thus, low preload leads to low EDV, which results in lower generated pressure and ultimately smaller stroke volume.
Two-dimensional (2D) and three-dimensional (3D) echocardiography allows for the calculation of stroke volume. The drawback of stroke volume as a measure of left ventricular function is that it ignores the ability of the ventricle to generate pressure. This is evident from Figure 1, which demonstrates that stroke volume is the difference between ESV and EDV, which can be calculated without considering pressure (the y-axis). Moreover, stroke volume also ignores the ability of the ventricle to shorten. These drawbacks become clear when examining patients with dilated cardiomyopathy (DCM). These patients may have normal stroke volumes, due to their large ventricular volumes, despite severe impairment of left ventricular function.
The ability to generate pressure can be calculated by estimating stroke work (SW).
Stroke work (SW)
In physics, work is equivalent to the product of power (f) and distance (d). The work required to move an object is the product of the force needed to move the object and the distance the object is moved. With regards to the left ventricle, the object is blood, and the force is the pressure generated by the left ventricle. Stroke work is the work performed to move blood from the ventricle into the aorta.
Stroke work is represented by the area within the pressure-volume loop in Figure 1. In vivo measurement of stroke work requires continuous measurement of ventricular pressure and volume during the cardiac cycle, which is not technically feasible. However, stroke work can be approximated as the product of stroke volume and mean arterial pressure (MAP). This does, however, result in an underestimation of stroke work.
Cardiac work (CW) is the product of heart rate (HR) and stroke work (SW):
CW = HR • SW
(SW = SV • MAP)
Frank-Starling’s law (mechanism)
Stroke volume is greater in the supine position, as compared with an upright position. This is because venous return increases in the supine position. More blood flows back to the heart, leading to increased ventricular filling (EDV). The left ventricle responds to increased EDV by automatically increasing stroke volumes. It follows that the heart can adapt its stroke volumes to variations in left ventricular filling. This phenomenon is called Frank-Starling’s mechanism (law).
Frank and Starling discovered that an increase in Left Ventricular End Diastolic Pressure (LVEDP) leads to stronger contractions and greater stroke volumes. This mechanism is independent of neurohumoral stimuli, although such stimuli can adjust the intensity of the mechanism. As evident in Figure 3, the Frank-Starling curve is modified by afterload and inotropy of the myocardium.
A rather simple cellular mechanism seems to explain Frank-Starling’s mechanism. When ventricular filling is increased, the myocardial fibers and their sarcomeres, are stretched. This results in troponin C becoming more sensitive to calcium (sensitivity depends on sarcomere length), which accelerates the interaction between actin and myosin, and ultimately produces more force.
The difference between contractility and contractile function
There is a discreet difference between contractility and contractile function.
Contractility describes the intrinsic ability of the myocardium to contract, regardless of preload and afterload. Contractility is the ability of individual muscle fibers to shorten. Contractility is not studied with echocardiography.
Contractile function describes the ability of the myocardium, in a given hemodynamic state (at certain preload and afterload conditions). This is synonymous with systolic function and can be estimated by echocardiography.
Preload is the force that stretches myocardial fibers during diastole. Stretching can be described by end-diastolic pressure, end-diastolic volume or end-diastolic diameter. However, neither pressure, volume, nor diameter is normalized. Therefore, preference should be given to preload adjusted for the surface area of the ventricle, which is equivalent to end-diastolic wall tension (discussed below).
Preload reserve is an important parameter. It indicates how much reserve there is in preload. A ventricle with a large preload reserve can receive a larger volume of blood (i.e increase its LVDP). In upright position, all healthy individuals have a large preload reserve, which becomes useful during physical activity. In the supine position, however, preload reserve is small. This is because venous return increases so much in the supine position, that the ventricle is already stretched and operates at or close to its reserve.
Afterload is the force that the myocardium generates during systole. Afterload can also be described in terms of wall tension, which means that the force is adjusted for surface area. Afterload depends on the thickness of the myocardium. Individuals with high blood pressure (high afterload) often develop a compensatory hypertrophy, which may normalize afterload per surface area.
Wall tension is the force applied to the wall of the ventricle. The force should be adjusted for the ventricular surface area, resulting in wall tension per surface area (σ):
σ = (p·r)/2·t
p = transmural pressure; r = ventricular radius; t = wall thickness.
Transmural pressure (p) is the pressure in the left ventricle. It can be approximated; this is done by approximating p to systolic pressure (measured as conventional blood pressure).