Metabolism of the isolated frog's heart: written for the Gunning Victoria Jubilee Prize in Materia Medica, 1932

When the task of writing this essay was undertaken, it was hoped that it would be possible to conclude it by presenting a complete picture of the chemical processes which occur during contraction and relaxation processes in the isolated frog's heart, analogous to what is already known concerning skeletal muscle. However, this has proved to be, as yet, impossible, and we must confine ourselves to giving the various conclusions at which we have, so far, been able to arrive.Our preliminary work suggested that the metabolic processes occurring during contraction of the isolated frog's heart were very different from those occurring in the case of skeletal muscle. Later work, however, shows that the two processes are probably essentially very similar. These experiments are concerned with the source of the energy necessary for the contraction relaxation process. All work on this subject in the case of skeletal muscle points to carbohydrate being by far the chief source of energy. In the case of the isolated heart, however, under completely aerobic conditions, carbohydrate metabolism forms normally,at the most, only 25 per cent. of the total metabolism, and when the heart is fed with glucose and insulin 45 per cent. The latter figure is probably too high, because glucose, when added to the isolated heart, poisons the heart, and this high carbohydrate consumption may be partly due to post mortem lactic acid production.Of the remaining metabolism none is due to oxidation of fat, and 36 per cent. is due to oxidation of proteins with consequent production of nitrogenous end products. This figure is probably slightly too low owing to the loss of ammonia to the atmosphere. The remaining 20 per cent. of the total metabolism is still unaccounted for, and in order to balance the oxygen consumption with the metabolic changes it is necessary to assume the production during perfusion of reducing and fermentable substances amounting to about 20 per cent. of the initial content. This assumption is also necessary to account for the fact that the carbohydrate content of the heart and perfusion fluid together only falls to the level of the control values after an oxygen consumption of about 6 c.c. per gm. of heart, a quantity which is used by a heart after about 4 hours' perfusion with normal ringer's fluid.These figures only hold when the heart is receiving a thoroughly adequate supply of oxygen. Any tendency to anaerobiosis increases the loss of carbohydrate with formation of lactic acid, and simultaneously decreases the nitrogenous metabolism. This may account for the great difference between the source of energy for contraction -relaxation processes in cardiac and skeletal muscle. The former is essentially an aerobic organ, and the isolated heart in these experiments was thoroughly oxygenated. The latter, on the other hand, is never so fully oxygenated, and consequently its normal metabolism cannot be expected to be the same as that of the isolated heart.Under anaerobic conditions the only important source of energy is the conversion of carbohydrate to lactic acid. Unlike skeletal muscle, heart tissue is unable to neutralise any considerable quantity of lactic acid. As small a concentration as 0.15 per cent. of lactic acid rapidly stops the heart. Consequently the heart is unable to function anaerobical: unless it is able to excrete rapidly the lactic acid it produces. The excretion of lactic acid depends on the reaction of the perfusion fluid. With neutral Ringer's fluid lactic acid is excreted extremely slowly and sufficiently, accumulates inside the heart to kill it in less than one hour. At the same time the mechanical efficiency falls almost immediately practically to zero. When the perfusion fluid is alkaline Ringer's solution (buffered at pH 8.5), excretion of lactic acid occurs freely and the heart is able to survive for several hours. The limiting factor in this case is the supply of available carbohydrate.When glucose is added to alkaline perfusion fluid the heart is able to use this supply, conserving, and even adding to, its own store, and to continue working for many hours, producing large quantities of lactic acid.Therefore the effect of oxygen lack upon the isolated heart depends primarily upon the reaction of the perfusion fluid and secondly upon the availability of carbohydrate. The availability of the heart's store of carbohydrate appears to vary. Under aerobic conditions, the total carbohydrate content of the heart may be reduced after 24 hours to between 0.3 and 0.4 per cent. Under anaerobic conditions, with alkaline Ringer's fluid and in the absence of added glucose, the total carbohydrate content of perfused hearts does not fall below 0.77 per cent. It appears, therefore, that 0.3 to 0.4 per cent. cannot be used at all, and about 0.8 per cent. cannot be used under anaerobic conditions. This suggests that part of the carbohydrate store of the heart is only made available when protein is being metabolised simultaneously.We have therefore practically a complete picture of the metabolic processes which supply energy to the isolated frog's heart.Of the chemical processes which are more intimately connected with the contraction mechanism, little is yet known, with the exception of changes in the phosphorus compounds. However, results obtained so far suggest that these processes are somewhat similar to the corresponding processes in skeletal muscle. In some respects, for example in,the thorough oxygenation possible, heart tissue forms an ideal system for the further study of the chemical processes taking part in the contraction of muscle. We therefore look forward to the immediate future confident that results of at least as great interest as those already published, will be forthcoming