The Frank -Starling Relationship: Cellular and Molecular Mechanisms

Abstract

It is probably not an exaggeration to suggest that the modern era of cardiovascular research began with the classical studies of Otto Frank and Ernest Starling on the relationship between end diastolic volume and systolic function in the isolated heart (Frank, 1895; Patterson and Starling, 1914). From the standpoint of integrative physiology, their work provided a mechanism for linking cardiac output to peripheral vascular perturbations (blood volume, venous compliance, skeletal muscle activity, etc.) which can alter central venous pressure and, hence, the degree of stretch of the myocardial muscle fibers. Their findings, still valid, are central to our understanding of the events that take place in such situations as exercise, hemorrhage, and congestive heart failure. For the muscle physiologist, their work provided the challenge of explaining cardiac function in terms of the basic cellular and molecular mechanisms which control force generation and shortening in striated muscle fibers. This effort has continued to the present day. Building on recent advances in the areas of muscle ultrastructure, contractile protein function, and Ca²⁺ regulation, it is now possible to formulate a generally plausible mechanism which accounts, at least in large part, for the linkage between ventricular filling pressure and systolic performance. The intracellular signaling pathways which mediate this process remain to be clarified.

“The law of the heart is thus the same as the law of muscular tissue generally, that the energy of contraction, however measured, is a function of the length of the muscle fibre”. Starling, E.H., The Linacre Lecture on the Law of the Heart, 1918, Longmans, Green and Co., London.