CO = SV * PR.

The stroke volume of the left ventricle is ultimately determined by the interaction between its preload, the contractile state of the myocardium and the afterload that the ventricle faces. Unfortunately, there is no simple measure of the 'contractile state' and as a result, there is no single equation which describes the relationship between these three parameters.

Preload.
That the 'preload' or stretch on myocardial fibres at the end of diastole had a significant effect on the subsequent force of contraction was recognised by the physiologist Otto Frank at the end of the nineteenth century ¹ (Figure 1).

This fundamental relationship has since been analysed in great detail and the adjustment of preload by blood volume transfusion or depletion remains one of the most important therapeutic manoeuvres in acute cardiovascular medicine.

In practice, such volume adjustments can be made by various means:

1. Circulating blood volume can be increased by the administration of fluid, or reduced by the use of diuretics and / or fluid restriction.

2. Venous return can be varied by the adoption of a head-down or head-up posture.

3. Venous capacitance can be altered by the use of vasoconstrictor or vasodilator therapy.

Contractile State.
In its strictest sense, the term 'contractility' refers to the inotropic state of the myocardium - that is, the force and velocity with which the myocardial fibres contract. This can be easily measured in an isolated muscle preparation under specified loading conditions, but is notoriously difficult to measure in the intact human.

In clinical practice, various contraction-phase indices such as velocity of fibre shortening, peak rate of ventricular pressure rise and end-systolic pressure:volume relationship (Figure 2) are used, but they are all affected by loading conditions to a greater or lesser degree.

The 'chronotropic' or 'rate' state of the intact heart should also be incorporated into any clinical definition of 'contractility' - because variations in the pulse rate can have obvious, important effects on the cardiac output and manipulation of pulse rate by the use of positive or negative chronotropes can be an important therapeutic manoeuvre in sick patients.

It is not possible to make any precise measurements of contractility with a PAC, although it is possible to make reasonable inferences about the contractile state by the use of ventricular function curves (Figure 1). This concept has been developed by Barash et al who have described the use of a 'Hemodynamic Tracking System' which defines the relationship between LVSWI and PAOP in patients with normal, slightly depressed and severely depressed ventricular function ².

Adjustment of both the inotropic and chronotropic state of the heart by the use of inotropic drugs is commonly practised in cardiovascular medicine.

Afterload.
In physiological terms, afterload can be defined as 'The sum of all those forces which oppose ventricular muscle shortening during systole' - although in a clinical sense it is probably more useful to consider systemic vascular resistance as the appropriate measure.

In isolated cardiac muscle, there is an inverse relationship between afterload and the initial velocity of shortening of the muscle (Figure 3). This would suggest a potential dependance of cardiac output on afterload. In fact, in the intact human, the output of the normal heart is relatively unaffected by changes in vascular resistance until afterload becomes quite extreme (Figure 4). This is probably because an increase in afterload leads to an almost immediate, secondary increase in preload by a 'damming up' of the blood within the left ventricle. This, in turn, increases end-diastolic volume which enhances contractility through the Frank-Starling mechanism. In contrast, if myocardial function is severely depressed, cardiac output may become crucially afterload-dependent as illustrated in Figure 4.

Thus, 'sick' hearts can be considered to be relatively preload independent but afterload dependent while the reverse is true for 'healthy' hearts. As a result, 'afterload reduction' (reduction of systemic vascular resistance by the use of appropriate vasoactive drugs) is of the greatest benefit in those in whom myocardial function is most depressed.

The role of blood viscosity and, indirectly, haemoglobin concentration in determining SVR is often overlooked. Although haemodilution is not commonly used as a therapeutic manoeuvre for afterload reduction, inadvertent haemodilution is often a concomitant of serious illness. Haematocrit and fibrinogen are the most important determinants of blood viscosity and, in turn, contribute significantly to vascular resistance. These relationships are illustrated graphically in Figure 5. Because blood is a non-Newtonian fluid, there is no simple expression to relate SVR to haematocrit and fibrinogen levels, however, it is easy to demonstrate the completely passive increase in venous return ³ and cardiac output which occur during haemodilution ⁴.

Finally, it should not be forgotten that there is a degree of ventricular interdependence which can determine ventricular performance ⁶. - The position of the interventricular septum (IVS) can alter the compliance of each ventricle under altered loading conditions with secondary effects on contractility. This effect is not usually important, but can become so in conditions such as tension pneumothorax, tamponade, right ventricular infarction etc.

1. Frank O: Zur Dynamik des herzmuskels. Ztschr fur Biol 32:370, 1895

2. Barash PG, Chen Y, Kitahata LM et al The Hemodynamic Tracking System. Anesth. Analg. 59:169 (1980)

3. Guyton AC, Richardson TQ Effect of hematocrit on venous return. Circ Res 9:157-163, 1961

4. LeVeen HH, Ip M, Ahmed N et al Lowering blood viscosity to overcome vascular resistance. Surg Gynecol Obstet 150:139-149, 1980

5. Eckmann DM, Bowers S, Stecker M, Cheung AT Hematocrit, volume expander, temperature, and shear rate effects on blood viscosity. Anesth Analg 2000 Sep;91(3):539-45

6. Taylor RR, Covell JW, Sonnenblick EH et al: Dependence of ventricular distensibility effect on filling of the opposite ventricle. Am J Physiol 218:711, 1967

Last edited on: 14/11/2000