Energy sources for contraction of the rat ventricle in phosphate media.

Various substrates were tested for their ability to restore the amplitude of contraction of hypody-namic electrically-stimulated rat ventricle strips suspended in a phosphate-buffered medium. Greatest recovery of the contractile activity was obtained with pyruvate; lactate, /3-hydroxybutyrate and acetate were more effective than succinate and glucose. The finding that glucose, in contrast to pyruvate, was relatively ineffective as an energy source for contraction, when a phosphate-buffered medium was employed, suggests that the defect was due to a rate-limiting step in the conversion of glucose to pyruvate, rather than to an impairment in the functioning of the Krebs cycle. P HOSPHATE-BUFFERED media are commonly employed in the investigation of the positive inotropic action of the cardiac glycosides. However, evidence has recently been presented which indicates that important alterations in cellular function occur when phosphate is substituted for bi-carbonate in physiologic m e d i a. 1 2 5 The present investigation on the energy sources for the rat ventricle preparation was undertaken in order to provide data that may be pertinent to tho elucidation of the sequence of events in isolated ventricle preparations that lead to the hypodynamic state and the reversal of this state by the cardiac glycosides. The data may also be of value in the interpretation of results obtained in other investigations where phosphate-buffered media are employed. METHODS Male albino nits (150 to 200 Gm.) were killed by decapitation. A strip was prepared from the right ventricle according to the technic of Feigen and associates. 4 The contractions were recorded under conditions described previously. 6 The reference phosphate medium contained 0.9 per cent NaCl, 0.042 per cent KC1, 0.036 per cent CaCl ; , and 1 mM sodium phosphate buffer (pH 7.4), and was adjusted to pH 7.4 with 0.1 N sodium hydroxide. The tissue was suspended in 150 cc. of substrate-free medium at 27 C. which was continuously aerated with oxygen. The strip was stimulated at a constant rate of 100 per minute. In the absence of added substrate, the amplitude of contraction gradually increased to a maximum value during the equilibration period and then steadily declined over a period of hours. The initial amplitude refere to the maximum amplitude of contraction attained at the end of the equilibration period. The mean initial amplitude in 81 experiments with the reference phosphate medium was 41 mm. (optical magnification of 65). Substances were added when the amplitude had declined to …