AN EXPERIMENTAL-MODEL OF HYPOXIA ON ISOLATED RAT-HEART IN RECIRCULATING SYSTEM - STUDY OF FATTY-ACID METABOLISM WITH AN IODINATED FATTY-ACID

An experimental model of hypoxia was developed on isolated rat heart t o study the effects of hypoxia on cardiac performance and metabolism. Fatty acid (FA) metabolism was explored by external detection with a l abelled FA, iodohexadecenoic acid (IHA). Hearts, after 30 min preperfu sion in an open system, were transferred in a recirculating system for 40 min and perfused with oleate, glucose, lactate, pyruvate and IHA, either in normoxia (pO(2)=660 mmHg) or in hypoxia (pO(2)=220 mmHg). Af ter 40 min hypoxic recirculation, oxygen uptake and dynamic parameters , except the heart rate, decreased respectively by 56% and 44%, and re mained constant throughout the perfusion. Glucose utilization increase d 2 fold, endogenous glycogen fell by 50% and lactate + pyruvate produ ction increased 3 fold, showing a stimulation of glycolysis. Oleate up take decreased by 28%, while triglycerides content remained higher. Th e ATP/ADP ratio decreased by 24%. Conversely to oleate, IHA uptake was not significantly modified, but its intracellular fate showed a highe r radioactivity in all lipid fraction : polar lipids, diglycerides, fr ee FAs and triglycerides. beta oxidation of IHA, evidenced by iodide p roduction, decreased by 39%. The external detection of cardiac radioac tivity allowed us to obtain time-activity curves that were analyzed wi th a 4-compartment mathematical model. The data evidenced an esterific ation ratio significantly higher in hypoxia. The metabolism of IHA as estimated by the intracellular analysis or, in a non-invasive way, by external detection, was similar to the metabolism of oleate. Thus, lip id metabolism, in hypoxia, can be explored by external detection with IHA.