Re-visiting the Frank-Starling nexus

Well over a century ago, Otto Frank, working at Carl Ludwig's Institute of Physiology in Munich, studying the isolated, blood-perfused, frog heart preparation, demonstrated that there are two distinct pressure volume relations in the heart: one for isovolumic twitches and a second (located inferiorly) for after loaded twitches. Whereas Starling, working at UCL two decades later, referenced Frank's publication (to the extent of re-printing its seminal Figure), he appeared not to have tested Frank's finding. Hence, he remained silent with respect to Franks' contention that cardiac pressure-volume relations are contraction-mode-dependent. Instead, he concluded that "The energy of contraction, however measured, is a function of the length of the muscle fibre" - a conclusion that has become known (at least in the English-speaking world) as 'Starling's Law of the Heart'. This provides us with at least three conundra: (i) why did Starling present only one pressure-volume relation whereas Frank had previously found two, (ii) why, then, do we speak of The Frank-Starling relation, and (iii) how did Frank become largely forgotten for twelve decades among English speakers? This review will attempt to address and comment on these conundra. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).