AJP - Heart and Circulatory Physiology, Vol 242, Issue 5 818-H826, Copyright © 1982 by American Physiological Society
Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog
J. L. Swain, R. L. Sabina, P. A. McHale, J. C. Greenfield Jr and E. W. Holmes
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.
