DE MOTU CORDIS : CELLULAR PHYSICS AND CHEMISTRY

SUMMARY William Harvey regarded himself as an anatomist although he provided the first physiological analysis of the circulation. In this he used the physical concepts which Galileo taught while Harvey was at Padova, as well as the experimental method and inductive‐deductive sequence of logic which the New Philosophy recommended as an approach to understanding. His hypothesis was supported shortly after his death by Malpighi's discovery of the capillaries in 1661. The circulation of the blood was expounded in medical schools in physical terms. It was not until late in the eighteenth century that quantitative chemistry began, and at that time the first suggestion that the heart might require energy for its pumping action was made by Felice Fontana of Bologna. During the nineteenth century physical analysis of heart action in terms of pressures, velocities, sound and electrical activity went forward. The metabolic background was, however, slow to develop, and only in the nineteen‐thirties was it clear that oxygen and lactate were the energy sources of heart action. In the last ten years some attempt at synthesis of the physical and the chemical background of heart action has been made. Single cells studied chemically and physically yield a picture of the heart as a whole. Using intracellular electrodes and metabolic blocking agents it is found that the duration of the refractory period is lessened in the absence of oxygen or in the presence of agents decoupling oxidative phosphorylation. The rest pause before any particular action potential of the cell determines the length of that action potential and therefore of the refractory period. High energy phosphate is probably necessary for the maintenance of refractoriness. Agents (dinitrophenol, digitalis glycosides, sodium azide or hypoxia) which reduce the duration of the action potential also slow the heart, when innervation of the heart has been interrupted. It is possible that the initiation of heart beat is an active process of ion transfer employing the same energy sources as those producing the refractory period. The physical manifestations of heart action studied by Harvey thus meet the chemical sources of energy at the cellular level where analysis of the motion of the heart must ultimately take place.