The determinants of cardiac output (CO) are heart rate (HR) and stroke volume (SV).

CO = HR × SV

This relationship can be simplified using the determinants of SV—end-diastolic volume (EDV) and ejection fraction (EF).

CO = HR × EDV × EF

Therefore, the only way cardiac output can increase or decrease is if heart rate, end-diastolic volume, and/or ejection fraction increase(s) or decrease(s).

There are many factors that affect heart rate, end-diastolic volume, and ejection fraction. Hence, these factors change cardiac output. Heart rate may be affected by a variety of drugs and inherent conduction abnormalities. Factors that limit the increase in heart rate, such as β-blockers, atrioventricular block, and sick sinus syndrome, negatively affect the increase in cardiac output.

End-diastolic volume (preload) increases with an increase in intravascular volume and vice versa. Also, conditions such as restrictive cardiomyopathy, pericardial effusion, and constrictive pericarditis that limit ventricular filling decrease diastolic volume and hence cardiac output.

Ejection fraction decreases with decreased preload, increased afterload, and decreased contractility. Ejection fraction increases with increased preload, decreased afterload, increased contractility, and increased heart rate.

Contractility, by affecting ejection fraction, changes cardiac output. Contractility is easy to conceptualize but difficult to measure. Simplistically, ejection fraction would seem to be an excellent measure of contractility. However, because ejection fraction is affected by afterload, preload, heart rate, and contractility, it is not a pure measure of contractility. Contractility can change in response to either positive or negative inotropic agents.

As is apparent from this discussion, truly understanding a basic relationship such as CO = HR × EF × EDV allows one to truly understand cardiovascular physiology and how diseases and different treatment strategies affect cardiac function.

There are several other relationships with which one should be acquainted. These are described in the following sections.

Ohm’s law describes the relationship between pressure, flow, and resistance. Understanding this relationship is essential to understand, for example, the difference between pulmonary hypertension and pulmonary vascular obstructive disease, the effect of left-to-right shunts on pulmonary artery pressure, and the effects of pulmonary artery and systemic vascular resistances on the volume of left-to-right and right-to-left shunts.

It is obvious from this relationship that increased pulmonary artery pressure could result from increased resistance in the pulmonary bed or increased flow into the pulmonary bed or both.

It also is clear from this relationship that flow decreases as resistance increases.

This explains why a drug that decreases systemic vascular resistance (afterload reduction) increases cardiac output (Q).