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International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1990 Oct;71(5):727–739.

Does allopurinol prevent myocardial injury as a result of hypoxia-re-oxygenation in rats?

N Miwa-Nishimura 1, H Kanaide 1, S Abe 1, M Nakamura 1
PMCID: PMC2001971  PMID: 2206993

Abstract

We made use of the xanthine oxidase inhibitor allopurinol and examined changes related to myocardial injury of the rat heart during hypoxia-re-oxygenation. The rat heart was perfused using the Langendorff method. With low-oxygen perfusion for 60 min in a solution saturated with mixed gases of 95% N2 + 5%O2, contractile tension did not develop and tension development was not restored upon re-oxygenation. During hypoxia, the resting tension increased (4.1 g) in the absence of allopurinol. In the allopurinol-administered group (100 microM), contractile tension did not develop during hypoxia; however, the development of tension was restored (18%) upon re-oxygenation. The elevation of resting tension was less (3.2 g) during hypoxia. All events related to the myocardial injury (inhibition of Na+, K(+)-ATPase activities, generation of malondialdehyde, extracellular leakage of creatine kinase) after low-oxygen perfusion for 60 min and re-oxygenating perfusion for 30 min were mild in the allopurinol treated group, compared with findings in the non-administered group. Tissue ATP at 10 min after low-oxygen perfusion was of a significantly high value in the allopurinol treated group (13.2 mumols/g dry weight), compared with findings in the group not given the drug (8.4 mumol/g dry weight). Sixty minutes after low-oxygen perfusion, tissue ATP in the allopurinol group also remained high, compared with the group not given the drug. Although the intensity of the epicardial NADH fluorescence indicated that the extent of inhibition of aerobic energy production during 10 min of low-oxygen perfusion was the same for both groups, lactate was produced in large quantities in the allopurinol treated group, hence energy generation advanced with glycolysis. These observations suggest that allopurinol prevents myocardial injury as a result of hypoxia-re-oxygenation. In the low-oxygen perfusion period, generation of energy is maintained and improved with glycolysis and there is a reduction in the generation of free radicals and an inhibition in lipid peroxidation.

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Selected References

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

  1. Arnold W. L., DeWall R. A., Kezdi P., Zwart H. H. The effect of allopurinol on the degree of early myocardial ischemia. Am Heart J. 1980 May;99(5):614–624. doi: 10.1016/0002-8703(80)90736-x. [DOI] [PubMed] [Google Scholar]
  2. Garlick P. B., Davies M. J., Hearse D. J., Slater T. F. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res. 1987 Nov;61(5):757–760. doi: 10.1161/01.res.61.5.757. [DOI] [PubMed] [Google Scholar]
  3. Guarnieri C., Flamigni F., Caldarera C. M. Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart. J Mol Cell Cardiol. 1980 Aug;12(8):797–808. doi: 10.1016/0022-2828(80)90081-4. [DOI] [PubMed] [Google Scholar]
  4. Harmsen E., de Tombe P. P., de Jong J. W., Achterberg P. W. Enhanced ATP and GTP synthesis from hypoxanthine or inosine after myocardial ischemia. Am J Physiol. 1984 Jan;246(1 Pt 2):H37–H43. doi: 10.1152/ajpheart.1984.246.1.H37. [DOI] [PubMed] [Google Scholar]
  5. Hearse D. J., Manning A. S., Downey J. M., Yellon D. M. Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion? Acta Physiol Scand Suppl. 1986;548:65–78. [PubMed] [Google Scholar]
  6. Hirsch M. S., Wormser G. P., Schooley R. T., Ho D. D., Felsenstein D., Hopkins C. C., Joline C., Duncanson F., Sarngadharan M. G., Saxinger C. Risk of nosocomial infection with human T-cell lymphotropic virus III (HTLV-III). N Engl J Med. 1985 Jan 3;312(1):1–4. doi: 10.1056/NEJM198501033120101. [DOI] [PubMed] [Google Scholar]
  7. Jennings R. B., Reimer K. A. Lethal myocardial ischemic injury. Am J Pathol. 1981 Feb;102(2):241–255. [PMC free article] [PubMed] [Google Scholar]
  8. Kanaide H., Taira Y., Nakamura M. Transmural anoxic wave front and regional dysfunction during early ischemia. Am J Physiol. 1987 Aug;253(2 Pt 2):H240–H247. doi: 10.1152/ajpheart.1987.253.2.H240. [DOI] [PubMed] [Google Scholar]
  9. Kramer J. H., Mak I. T., Weglicki W. B. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation. Circ Res. 1984 Jul;55(1):120–124. doi: 10.1161/01.res.55.1.120. [DOI] [PubMed] [Google Scholar]
  10. Masuda M., Yonenaga K., Shiki K., Morita S., Kohno H., Tokunaga K. Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. Preservation of high-energy phosphates and regional function. J Thorac Cardiovasc Surg. 1986 Aug;92(2):255–263. [PubMed] [Google Scholar]
  11. Meno H., Kanaide H., Okada M., Nakamura M. Total adenine nucleotide stores and sarcoplasmic reticular Ca transport in ischemic rat heart. Am J Physiol. 1984 Sep;247(3 Pt 2):H380–H386. doi: 10.1152/ajpheart.1984.247.3.H380. [DOI] [PubMed] [Google Scholar]
  12. Nayler W. G., Poole-Wilson P. A., Williams A. Hypoxia and calcium. J Mol Cell Cardiol. 1979 Jul;11(7):683–706. doi: 10.1016/0022-2828(79)90381-x. [DOI] [PubMed] [Google Scholar]
  13. Nayler W. G. The role of calcium in the ischemic myocardium. Am J Pathol. 1981 Feb;102(2):262–270. [PMC free article] [PubMed] [Google Scholar]
  14. Peterson D. A., Asinger R. W., Elsperger K. J., Homans D. C., Eaton J. W. Reactive oxygen species may cause myocardial reperfusion injury. Biochem Biophys Res Commun. 1985 Feb 28;127(1):87–93. doi: 10.1016/s0006-291x(85)80129-7. [DOI] [PubMed] [Google Scholar]
  15. Philipson K. D., Nishimoto A. Y. Efflux of Ca2+ from cardiac sarcolemmal vesicles. Influence of external Ca2+ and Na+. J Biol Chem. 1981 Apr 25;256(8):3698–3702. [PubMed] [Google Scholar]
  16. Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta. 1978 Nov 15;90(1):37–43. doi: 10.1016/0009-8981(78)90081-5. [DOI] [PubMed] [Google Scholar]
  17. Zweier J. L., Flaherty J. T., Weisfeldt M. L. Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1404–1407. doi: 10.1073/pnas.84.5.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]

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