Myocardial fuel and energy balance, acute ischemia and diabetes.
When glucose-insulin-potassium (GIK) is infused, glucose supplies most of the energy demands of the heart. Fatty acid becomes the major substrate during fasting, pathologically increased work loads or insulin deficiency. Myocardial purine breakdown reflects myocardial energy status and influences coronary tone. Ischemia accelerates breakdown of ATP to AMP, which is further metabolized to adenosine, which causes vasodilatation and a blunted response to catecholamines. If normal circulation is restored, ADP and AMP are rapidly converted to ATP and purine metabolism is changed from degradation to salvage and de novo synthesis of purines. Ischemia impairs mitochondrial function, causing decreased capacity to oxidize fatty acids once aerobic conditions return. Thus, reperfusion with elevated plasma free fatty acids results in acyl-CoA accumulation in the heart. In diabetic animals, phosphorylation of AMP to ATP is defective in the heart, and AMP degradation is increased. Therefore, careful regulation of the blood sugar with concomitant lowering of plasma free fatty acids in diabetics with ischemic heart disease should improve myocardial salvage by preserving and repleting myocardial ATP. Thus, along with reestablishment of coronary flow and reduction in myocardial oxygen demands, may significantly reduce the morbidity of acute ischemia in diabetics.
McDaniel
H G
HG
Department of Medicine, VA Medical Center, Birmingham, AL 35233.
Jenkins
R L
RL
Digerness
S B
SB
Ong
R L
RL
D000208:Acute Disease; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism*
D000227:Adenine Nucleotides; D005227:Fatty Acids; D005947:Glucose