CARDIAC ACCUMULATION OF CITRATE DURING BRIEF MYOCARDIAL-ISCHEMIA AND REPERFUSION IN THE PIG IN-VIVO

Citrate is a key intermediate in energy metabolism and an inhibitor of phosphofructokinase of the glycolytic pathway. During myocardial isch aemia glycolysis is the main source of cardiac ATP. The aim of the pre sent study was to determine if myocardial ischaemia and reperfusion al ter cardiac tissue levels of citrate. Open-chest, anaesthetized pigs w ere subjected to 10 min of regional myocardial ischaemia by occlusion of the left anterior descending coronary artery, with and without repe rfusion, and to 10 min of global ischaemia by circulatory arrest. Citr ate, amino acids, glucose and NH3 were measured in biopsies. Ischaemia , whether regional or global, caused a 60-70% increase in tissue level s of citrate. During 1 min of reperfusion following regional ischaemia the level of citrate increased 460%, to approximate to 600 nmol g(-1) wet weight. The level of glutamate decreased by 20-33% (corresponding to 1300-2200 nmol g(-1) wet weight), indicating net consumption of th is amino acid during ischaemia. The level of aspartate decreased 50% i ndicating conversion of aspartate to oxaloacetate for the synthesis of citrate. Theoretically, the accumulation of myocardial citrate during brief ischaemia and early reperfusion is large enough to significantl y inhibit phosphofructokinase activity and could therefore affect the ability of the myocardium to increase the glycolytic rate in response to ischaemia. This could, however, be partly compensated by the metabo lism of myocardial glutamate.