Effect of short-term fasting on [123I] iodohexadecenoic acid metabolism in the isolated perfused rat heart. Validation of mathematical model by comparison with experimental measurements

Abstract In order to study metabolic modifications induced by short term fasting and their consequences on the uptake and intracellular fate of fatty acids iodine labelled in omega position, rats undergo a 36h fasting. Hearts are perfused in a Langendorff system with a glucose (11 mM) perfusion medium; [123I] hexadecenoic acid (IHA) is injected as a bolus. A comparison between time-activity curves p.i. demonstrates a much faster activity decrease for the hearts fasted animals. The intracellular analysis shows that short fasting did not significantly increase the myocardial uptake of fatty acids, but decreased the storage and increased the degradation of the fatty acids taken up. Mathematical analysis of the myocardial time-activity curves obtained by external detection provided results comparable to those of intracellular analysis. The coefficients of correlation between the values of the aqueous phases, organic phases and free fatty acids measured by intracellular analysis and calculated with the compart-mental model are consistently higher than 0.97. Consequently, this experimental model combined with mathematical analysis of the time-course of myocardial radioactivity after 123IHA administration appears to be very promising method for studying the effects of drugs or variations of energy substrate availability on myocardial fatty-acid metabolism.