Metabolic effects of adenosine in the isolated perfused rat heart

The effects of adenosine on myocardial substrate utilization were assessed in isolated Langendorff-perfused rat hearts. In unpaced hearts perfused at constant flow with insulin, adenosine inhibited oxidation of both glucose and palmitate with similar dose-dependency, without significant effects on effluent lactate+pyruvate. Significant effects of adenosine were observed at 0.1 microM adenosine. In a second series of paced hearts, perfusion pressure was kept constant during adenosine infusion by increasing the flow rate from 10 to 16.3 +/- 0.6 ml/min. Under these conditions, oxidation of both substrates was increased to a similar extent. Lactate+pyruvate output and total glycolytic flux were also increased. At zero or low insulin concentrations, the increases in substrate oxidation were similar to those seen at high insulin, but increases in lactate and pyruvate output and total glycolytic flux were abolished. It is concluded that adenosine does not preferentially increase glucose oxidation in this model.