[Model for the continuous determination of cell metabolism].

Using the isolated heart of guinea pigs according to the method of Langendorff a new model to study the metabolism of the myocardium is described. In one modification the heart is perfused by continuous flow of Ringer-Locke-solution, and the effluent is discarded. In the other modification the effluent is used for recirculation after saturation with oxygen. The advantage of this method is the possibility to measure oxygen consumption and production of acid metabolites by using pH-electrodes in the perfusion medium before and behind the heart. For measurement, the blood micro system and the acid-base analyzer is used. Many drugs and several unknown compounds have been examined for their influence on heart metabolism and could be classified as either stimulatory, inhibitory or ineffective. It is possible to study dose-response curves of these compounds to compare various compounds and to examine the cumulative or duration effects of combinations. The site of action of a compound and thus the mode of action can be examined as was demonstrated for alpha- and beta-blockers. Perfusion of the heart with glucose-free solution permits measurement of the effect of various energy sources for intensity and duration of effect. The well-known capacity of the heart to use lipids as an energy source could be demonstrated. When a pharmacologically active compound is added to the perfusion medium, glucose consumption, production of lactic acid and of other metabolites can be determined. The results obtained in the isolated heart were confirmed by corresponding tests in the intact animal. The model is highly sensitive to several classes of drugs. In some instances amounts of less than 1 mug can be determined.