S Pietri1, M Bernard, P J Cozzone. 1. Centre de Résonance Magnétique Biologique et Médicale, URA CNRS 1186, Faculté de Médecine de la Timone, France.
Abstract
STUDY OBJECTIVE: The aim was to show differences between the effects of various dietary long chain fatty acids (palmitic, oleic, linoleic, alpha and gamma linolenic acids) perfused in isolated rat hearts subjected to a sequence of high flow anoxia and subsequent reoxygenation. DESIGN: Isolated working rat hearts perfused with selected exogenous fatty acids were allowed an initial 30 min equilibration period followed by 60 min of high flow anoxia and 40 min of reoxygenation. Ventricular function and tissue contents of phosphorylated metabolites were monitored concomitantly using standard procedures and 31P magnetic resonance spectroscopy respectively. EXPERIMENTAL MATERIAL: Hearts were removed from male Wistar rats weighing 350-400 g. Results from eight hearts were pooled for each of the five fatty acids perfused. MEASUREMENTS AND MAIN RESULTS: High coronary flow maintained during anoxia led to an increased extracellular washout of lactate and only to mild intracellular acidosis, limiting myocardial damage by metabolites of anaerobic glycolysis. Under these conditions, marked differences between the classes of perfused fatty acids were observed. Hearts which received oleic acid showed the most depressed ventricular function and a greater depletion in high energy phosphates content. These deleterious effects were completely reversed by the separate administration of two fatty acid metabolism blocking agents, nicotinic acid and oxfenicine. Cardioprotection was enhanced by perfusion of polyunsaturated fatty acids (linoleic acid, alpha and gamma linolenic acids). Hearts perfused either with glucose or with palmitic acid behaved similarly and showed an intermediate functional and metabolic postanoxic recovery. CONCLUSION: This study documents the relation between the chemical structure of exogenous fatty acids used in heart perfusion and their ability to improve or impair postanoxic myocardial recovery. The cardioprotective effect of polyunsaturated fatty acids was documented by simultaneous evaluation of mechanical performance and metabolic response.
STUDY OBJECTIVE: The aim was to show differences between the effects of various dietary long chain fatty acids (palmitic, oleic, linoleic, alpha and gamma linolenic acids) perfused in isolated rat hearts subjected to a sequence of high flow anoxia and subsequent reoxygenation. DESIGN: Isolated working rat hearts perfused with selected exogenous fatty acids were allowed an initial 30 min equilibration period followed by 60 min of high flow anoxia and 40 min of reoxygenation. Ventricular function and tissue contents of phosphorylated metabolites were monitored concomitantly using standard procedures and 31P magnetic resonance spectroscopy respectively. EXPERIMENTAL MATERIAL: Hearts were removed from male Wistar rats weighing 350-400 g. Results from eight hearts were pooled for each of the five fatty acids perfused. MEASUREMENTS AND MAIN RESULTS: High coronary flow maintained during anoxia led to an increased extracellular washout of lactate and only to mild intracellular acidosis, limiting myocardial damage by metabolites of anaerobic glycolysis. Under these conditions, marked differences between the classes of perfused fatty acids were observed. Hearts which received oleic acid showed the most depressed ventricular function and a greater depletion in high energy phosphates content. These deleterious effects were completely reversed by the separate administration of two fatty acid metabolism blocking agents, nicotinic acid and oxfenicine. Cardioprotection was enhanced by perfusion of polyunsaturated fatty acids (linoleic acid, alpha and gamma linolenic acids). Hearts perfused either with glucose or with palmitic acid behaved similarly and showed an intermediate functional and metabolic postanoxic recovery. CONCLUSION: This study documents the relation between the chemical structure of exogenous fatty acids used in heart perfusion and their ability to improve or impair postanoxic myocardial recovery. The cardioprotective effect of polyunsaturated fatty acids was documented by simultaneous evaluation of mechanical performance and metabolic response.