[Myocardial metabolism abnormalities during ischemia and reperfusion].
Normal cardiac function requires adequate oxygen and substrate (fatty acids, glucose lactate) supply for the energetic requirements of the myocardium. Ischaemia induces abnormalities in the production and excretion of products of myocardial metabolism. During ischaemia, the equilibrium which exists during aerobic respiration between the beta-oxidation of fatty acids and carbohydrates and which generates ATP is disturbed. Pyruvate oxidation and beta-oxidation of fatty acids decrease, and ATP is mainly produced by anaerobic glycolysis. Under these conditions, intracellular glycogen is mobilised, the lactate and protons accumulate in the cardiomyocyte. If reperfusion occurs before irreversible lesions are produced, then functional recovery is possible and is mostly dependant on the type of energetic substrate available. Circulating fatty acids are produced in large quantities after ischaemia: their beta-oxidation, which is then the principal source of ATP, may contribute to the aggravation of contractile dysfunction during reperfusion and accentuate or generate arrhythmias. The decoupling between acceleration of anaerobic glycolysis and the defect of pyruvirate oxidation (inhibition of pyruvirate dehydrogenase) participate in a significant fashion to the accumulation of protons. Rapid correction of intracellular acidosis during reperfusion by activation of the Na+/H+ exchanger, coupled with the accumulation of intracellular Na+ induces a deleterious calcium overload via the Na+/Ca++ exchanger. These different aspects of intracellular metabolism constitute pharmacological targets for the development of future cardio-protective agents.
Service de cardiologie D, hôpital cardiologique et pneumologique Louis-Pradel, 59, boulevard Pinel, 69394 Lyon.
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D000138:Acidosis; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D005227:Fatty Acids; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase