PreClinical Insight: CV Physiology

Cardiac output increases or decreases in response to changes in heart rate or stroke volume. So how would venous return alter Stroke Volume?

In the late 19th century, Otto Frank found using isolated frog hearts that the strength of ventricular contraction was increased when the ventricle was stretched prior to contraction. This observation was extended by the elegant studies of Ernest Starling and colleagues in the early 20th century who found that increasing venous return to the heart, which increased the filling pressure of the ventricle, led to increased stroke volume.

This cardiac response to changes in venous return and ventricular filling pressure is intrinsic to the heart and does not depend on extrinsic neurohumoral mechanisms.

In honor of these two early pioneers, the ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return is called the Frank-Starling mechanism.

The red dashed curve represents a "normal" ventricular Frank-Starling curve. Increasing afterload or decreasing inotropy shifts the curve down and to the right. Decreasing afterload and increasing inotropy shifts the curve up and to the left. To summarize, changes in venous return cause the ventricle to move up or down along a single Frank-Starling curve; however, the slope of that curve is defined by the existing conditions of afterload and inotropy.

When venous return is increased, there is increased filling of the ventricle along its passive pressure curve leading to an increase in end-diastolic volume. If the ventricle now contracts at this increased preload, and the afterload and inotropy are held constant, the ventricle empties to the same end-systolic volume, thereby increasing its stroke volume.

The normal ventricle, therefore, is capable of increasing its stroke volume to match physiological increases in venous return. This is not, however, the case for ventricles that are in failure.