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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Jan;79(2):655–659. doi: 10.1073/pnas.79.2.655

Derangements in myocardial purine and pyrimidine nucleotide metabolism in patients with coronary artery disease and left ventricular hypertrophy.

J L Swain, R L Sabina, R B Peyton, R N Jones, A S Wechsler, E W Holmes
PMCID: PMC345805  PMID: 6210911

Abstract

Studies in animal models of myocardial ischemia and left ventricular hypertrophy have demonstrated a number of derangements in purine and pyrimidine nucleotide content of myocardium that are postulated to play a role in the pathogenesis of muscle dysfunction in these disorders. The present study examined myocardium of patients with coronary artery disease, left ventricular hypertrophy, or neither of these two abnormalities, to determine whether derangements in purine and pyrimidine nucleotide metabolism occur in humans. In patients with coronary artery disease, endocardial content of ATP, GTP, UTP, CTP, and creatine phosphate was reduced and ranged between 60% and 86% of the amount found in the epicardium. In patients without coronary artery disease or ventricular hypertrophy, endocardial content of these nucleotides was equal to or greater than that of epicardium. Endocardial and epicardial content of inosine was increased in patients with coronary artery disease, and after vein bypass grafting inosine content fell to the levels observed in myocardium of patients with normal coronary arteries. In patients with left ventricular hypertrophy, endocardial content of ATP, GTP, UTP, CTP, and creatine phosphate was also reduced and ranged between 64% and 88% of the epicardial content. In contrast to results obtained in patients without left ventricular hypertrophy, epicardial content of GTP, UTP, and CTP was increased by 131%, 123%, and 132% in hypertrophied myocardium. Thus the changes noted in myocardial nucleotide content in patients are similar to those noted in animal models of occlusive coronary disease and ventricular hypertrophy. These results suggest that the pathophysiological abnormalities in nucleotide metabolism noted in animal models also occur in human myocardium.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison T. B., Ramey C. A., Holsinger J. W., Jr Transmural gradients of left ventricular tissue metabolites after circumflex artery ligation in dogs. J Mol Cell Cardiol. 1977 Oct;9(10):837–852. doi: 10.1016/s0022-2828(77)80060-6. [DOI] [PubMed] [Google Scholar]
  2. Attarian D. E., Jones R. N., Currie W. D., Hill R. C., Sink J. D., Olsen C. O., Chitwood W. R., Jr, Wechsler A. S. Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. I. Myocardial blood flow and metabolism. J Thorac Cardiovasc Surg. 1981 Mar;81(3):382–388. [PubMed] [Google Scholar]
  3. Cunningham J. N., Jr, Adams P. X., Knopp E. A., Baumann F. G., Snively S. L., Gross R. I., Nathan I. M., Spencer F. C. Preservation of ATP, ultrastructure, and ventricular function after aortic cross-clamping and reperfusion. Clinical use of blood potassium cardioplegia. J Thorac Cardiovasc Surg. 1979 Nov;78(5):708–720. [PubMed] [Google Scholar]
  4. DeBoer L. W., Ingwall J. S., Kloner R. A., Braunwald E. Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5471–5475. doi: 10.1073/pnas.77.9.5471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Griggs D. M., Jr, Tchokoev V. V., Chen C. C. Transmural differences in ventricular tissue substrate levels due to coronary constriction. Am J Physiol. 1972 Mar;222(3):705–709. doi: 10.1152/ajplegacy.1972.222.3.705. [DOI] [PubMed] [Google Scholar]
  6. Jennings R. B., Hawkins H. K., Lowe J. E., Hill M. L., Klotman S., Reimer K. A. Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. Am J Pathol. 1978 Jul;92(1):187–214. [PMC free article] [PubMed] [Google Scholar]
  7. Koide T., Rabinowitz M. Biochemical correlates of cardiac hypertrophy. II. Increased rate of RNA synthesis in experimental cardiac hypertrophy in the rat. Circ Res. 1969 Jan;24(1):9–18. doi: 10.1161/01.res.24.1.9. [DOI] [PubMed] [Google Scholar]
  8. Kugler G. Myocardial release of lactate, inosine and hypoxanthine during atrial pacing and exercise-induced angina. Circulation. 1979 Jan;59(1):43–49. doi: 10.1161/01.cir.59.1.43. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Neely J. R., Rovetto M. J., Whitmer J. T., Morgan H. E. Effects of ischemia on function and metabolism of the isolated working rat heart. Am J Physiol. 1973 Sep;225(3):651–658. doi: 10.1152/ajplegacy.1973.225.3.651. [DOI] [PubMed] [Google Scholar]
  11. Reibel D. K., Rovetto M. J. Myocardial adenosine salvage rates and restoration of ATP content following ischemia. Am J Physiol. 1979 Aug;237(2):H247–H252. doi: 10.1152/ajpheart.1979.237.2.H247. [DOI] [PubMed] [Google Scholar]
  12. Sabina R. L., Swain J. L., Patten B. M., Ashizawa T., O'Brien W. E., Holmes E. W. Disruption of the purine nucleotide cycle. A potential explanation for muscle dysfunction in myoadenylate deaminase deficiency. J Clin Invest. 1980 Dec;66(6):1419–1423. doi: 10.1172/JCI109995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Vary T. C., Angelakos E. T., Schaffer S. W. Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart. Circ Res. 1979 Aug;45(2):218–225. doi: 10.1161/01.res.45.2.218. [DOI] [PubMed] [Google Scholar]
  14. Vial C., Font B., Goldschmidt D., Pearlman A. S., DeLaye J. Regional myocardial energetics during brief periods of coronary occlusion and reperfusion: Comparison with S-T segment changes. Cardiovasc Res. 1978 Aug;12(8):470–476. doi: 10.1093/cvr/12.8.470. [DOI] [PubMed] [Google Scholar]

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