Cardiac accumulation of citrate during brief myocardial ischaemia 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 ischaemia glycolysis is the main source of cardiac ATP. The aim of the present study was to determine if myocardial ischaemia and reperfusion alter cardiac tissue levels of citrate. Open-chest, anaesthetized pigs were subjected to 10 min of regional myocardial ischaemia by occlusion of the left anterior descending coronary artery, with and without reperfusion, and to 10 min of global ischaemia by circulatory arrest. Citrate, amino acids, glucose and NH3 were measured in biopsies. Ischaemia, whether regional or global, caused a 60-70% increase in tissue levels of citrate. During 1 min of reperfusion following regional ischaemia the level of citrate increased 460%, to approximately 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 this amino acid during ischaemia. The level of aspartate decreased 50% indicating 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 significantly 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 metabolism of myocardial glutamate.
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
B
B
Hassel
A
A
Ilebekk
T
T
Tønnessen
D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D019343:Citric Acid / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013552:Swine
D000596:Amino Acids; D019343:Citric Acid; D000641:Ammonia; D005947:Glucose