Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog.
Purine and pyrimidine nucleotides are essential energy sources for basic metabolic reactions and play important roles in protein, glycogen, and nucleic acid synthesis, cyclic nucleotide metabolism, and energy transfer reactions. Brief coronary occlusions (12 min) were produced in seven open-chest dogs, and repetitive myocardial samples were taken in order to determine the response of the nucleotide pool to ischemia and reperfusion. During ischemia adenosine 5'-triphosphate (ATP) decreased to 57% of control, and similar decreases occurred in the guanosine 5'-triphosphate (GTP), cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP), and nicotinamide adenine dinucleotide (NAD+) pools. The decrease in nucleotides was accompanied by an increase in nucleosides and bases. After 60 min of reperfusion the content of all nucleotides had increased but was still significantly less than nonischemic values. The content of nucleosides and bases decreased immediately upon reperfusion. In contrast, creatine phosphate (CP) fell to 10% of control during ischemia but rebounded to above control values immediately upon reperfusion. Thus depletion of all nucleotide pools occurs during ischemia, and with reperfusion nucleotide content is restored only slowly. Delayed repletion is not caused by a defect in mitochondrial synthesis of ATP because CP content is restored rapidly. The slow repletion of nucleotides may be secondary to loss of nucleotide precursors during reperfusion and may result in widespread alterations in myocardial metabolism.
D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D006439:Hemodynamics; D007511:Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism*; D010477:Perfusion; D012016:Reference Values; D013997:Time Factors
D009711:Nucleotides