Rediscovery of Otto Frank's contribution to science

Abstract

In the late 19th century, German physiologist Otto Frank (1865-1944) embarked on a near life-long research program of laying down the mathematical, methodological, and theoretical foundations in order to understand and define the performance of the heart and circulatory system in all their complexity. The existence of the "Frank-Starling law" testifies to this. Two of his seminal publications have been translated into English previously, introducing Frank's research on the dynamics of the heart and the arterial pulse to a wider audience. It is likely that there are a host of other comparable achievements and publications of Frank that are still unknown to the international scientific (cardiological and physiological) community. However, their influence can still be felt and seen in modern cardiology and cardio-physiology, such as in the development of modern interactive simulating and teaching programs. We have translated and commented on ten of these papers, which can be read in parallel with the German originals. These publications show a wealth of theoretical assumptions and projections regarding the importance of the sarcomere, the development of models of contraction, thermo-dynamical considerations for muscular activity, differences between cardiac and skeletal muscles, problems related to methodology and measurement, and the first pressure-volume diagram (published 120 years ago). These topics were envisioned by Frank long before they became a focus of subsequent modern research. Nowadays, frequent measurements of pressure-volume relationships are made in research using the pressure-volume conductance catheter technique. In commenting Frank's scientific topics, we try to show how interconnected his thinking was, and thus how it enabled him to cover such a wide range of subjects.

Solving a century-old conundrum underlying cardiac force-length relations

“…As the initial muscle length is reduced below optimal, the workloop ESSLR instantiates progressively closer to the isometric relation (remark 2). We note that remarks 1 and 2 are also valid for studies of whole hearts (31), papillary muscles (14,15,17), and myocytes (23), as recently presented diagrammatically (32). What has not been previously realized, however, is that the curvatures of this family of end-systolic curves for each preparation are essentially the same when normalized (Fig.…”

“…The first presentation of the cardiac end-systolic pressure-volume relation dates back over a century when, in 1899, Otto Frank (10) published a schematic diagram of his findings from studying the frog ventricle (for an English translation, see Refs. 10a,32,and 43). In his diagram, the pressure-volume relation arising from isovolumic contractions was located above that of afterloaded ejecting contractions, thereby explicitly showing the dependency of the cardiac end-systolic relation on the mode of contraction.…”

TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts

“…There is a particular length between sarcomeres at which the tension in muscle fibers is greatest, leading to the greatest contraction force. The Franck Starling phenomenon is the observation that ventricular output increases as preload (end-diastolic pressure) increases [50, 51].…”

Ejection Fraction and Espvr: A Study in the Mechanics of Left Ventricular Contraction

“…The calculation of the parameters V oL and E mL of the linear model of the ESPVR in a non-invasive way for reliable clinical applications is also a topic of high priority [5,70]. Finally the reader may wish to compare the present study with Otto Frank's original work on the pressure-volume relation in the left venbtricle as presented in a recent study [71].…”