Preload can be defined as the initial stretching of the cardiac myocytes prior to contraction and is related to the sarcomere length. Sarcomere length can not be determined in the intact heart so other indices of preload are used such as ventricular end-diastolic volume or pressure. These measures of preload, however, are not ideal because they do not accurately reflect sarcomere length. For example, with an acute increase in ventricular volume there is an increase in sarcomere length. However, in a chronically dilated ventricle the sarcomere length might be normal because of the addition of new sarcomeres in-series. End-diastolic pressure is also a poor index of preload because the actual stretching of sarcomeres, and hence ventricular volume, is determined by the compliance of the ventricle. Therefore, there can be an increase in end-diastolic pressure without an increase in preload due to a reduction in ventricular compliance as occurs in ventricular hypertrophy. Nevertheless, end-diastolic pressure, and particularly end-diastolic volume, are used as clinical indices of preload; however, care must be taken when interpreting the significance of these values.

In the normal heart, right ventricular preload is determined by the volume of blood that fills the ventricle at the end of passive filling and atrial contraction (i.e., the end-diastolic volume). Factors which can enhance ventricular preload include venous blood pressure (determined by venous blood volume and compliance), and the rate of venous return that is influenced by blood volume, gravity, and mechanical activity of muscles and the respiratory system. Ventricular compliance, as described above, determines the end-diastolic volume for any given intraventricular filling pressure. Heart rate, by affecting filling time, has a pronounced inverse effect on preload. For example, increasing heart rate alone will cause a nearly proportionate, reciprocal decrease in stroke volume because of reduced filling time (at increased heart rates the period of diastole is reduced more than systole). Atrial contraction (at resting heart rates) normally has little influence on ventricular preload because most ventricular filling is passive; however, at high heart rates, enhanced atrial contractility (due to sympathetic activation) will play a significant role in ventricular filling and in determining preload. Inflow resistance also affects ventricular preload. For example, in tricuspid valve stenosis the inflow resistance is increased and ventricular preload is reduced. In ventricular systolic dysfunction, when ventricular inotropy is diminished, the ventricular preload increases because of the inability of the ventricle to eject normal volumes of blood. This causes blood to "back up" in the ventricle and proximal venous circulation.

Left ventricular preload is determined by the same factors as the right, except that venous pressure is pulmonary venous pressure instead of central venous pressure.