Display options
Cite
Abd-Elfattah AS, Jessen ME, Lekven J, et al. Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury. Mol Cell Biochem. 1998;180(1):179-91
Abd-Elfattah, A. S., Jessen, M. E., Lekven, J., & Wechsler, A. S. (1998). Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury. Molecular and cellular biochemistry, 180(1), 179-91.
Abd-Elfattah, A S, et al. "Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury." Molecular and cellular biochemistry vol. 180,1 (1998): 179-91.
Abd-Elfattah AS, Jessen ME, Lekven J, Wechsler AS. Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury. Mol Cell Biochem. 1998 Mar;180(1):179-91. PMID: 9546645.
Copy Download .nbib Format: NLM
Share it on

Mol Cell Biochem. 1998 Mar;180(1):179-91.

Differential cardioprotection with selective inhibitors of adenosine metabolism and transport: role of purine release in ischemic and reperfusion injury.

Molecular and cellular biochemistry

A S Abd-Elfattah, M E Jessen, J Lekven, A S Wechsler

Affiliations

  1. Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0532, USA.

PMID: 9546645

Abstract

In a previous report, we have demonstrated that simultaneous inhibition of nucleoside transport and adenosine deaminase accumulates endogenous adenosine and protects the myocardium against stunning. The differential cardioprotective effects of erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA), a potent inhibitor of adenosine deamination but not transport, and p-nitrobenzylthioinosine (NBMPR), a selective blocker of adenosine and inosine transport, are not known. Thirty-seven anaesthetized adult dogs were instrumented to monitor left ventricular performance using sonomicrometery. Dogs were randomly assigned into four groups. The control group (n = 8) received only the vehicle solution. Treated groups received saline containing 100 microM EHNA (EHNA-group, n = 7), 25 microM NBMPR (NBMPR-group, n = 7), or a combination of 100 microM EHNA and 25 microM NBMPR (EHNA/NBMPR-group, n = 10). Hearts were subjected to 30 min of normothermic global ischaemia and 60 min of reperfusion while on bypass. Adenine nucleotides, nucleosides, oxypurines and NAD+ were determined in extracts of transmural myocardial biopsies using HPLC. TTC staining revealed the absence of necrosis in this model. Drug administration did not affect myocardial ATP metabolism and cardiac function in the normal myocardium. Ischemia caused about 50% ATP depletion and accumulation of nucleosides. The ratio between adenosine/inosine at the end of ischemia was 1:10, 1:1, 1:1 and 10:1 in the control, EHNA-, NBMPR- and EHNA/NBMPR-group, respectively. Upon reperfusion, both nucleosides washed out from the myocardium in the control and EHNA-group while retained in the myocardium in the NBMPR and EHNA/NBMPR groups. Ventricular dysfunction 'stunning' persisted in the control group (52%) and in the EHNA-treated group (32%) after 30 min of reperfusion. Significant improvement of function was observed in the EHNA group only after 60 min of reperfusion. LV function recovered in the NBMPR- and EHNA/NBMPR-treated groups during reperfusion. ATP recovery occurred only when animals were pretreated with the combination of EHNA/NBMPR and remained depressed in the control group and EHNA and NBMPR-treated groups. At post mortem, TTC staining revealed the absence of myocardial necrosis. Superior myocardial protection was observed with inhibition of nucleoside transport by NBMPR alone or in combination with inhibition of adenosine deaminase by EHNA. Selective blockade of nucleoside transport by NBMPR is more cardioprotective than inhibition of adenosine deaminase alone in attenuating myocardial stunning. It is not known why EHNA partially inhibit adenosine deaminase, in vivo.

References

  1. J Thorac Cardiovasc Surg. 1994 Aug;108(2):269-78 - PubMed
  2. J Pharmacol Exp Ther. 1986 Feb;236(2):494-9 - PubMed
  3. Am Heart J. 1990 Oct;120(4):808-18 - PubMed
  4. J Mol Cell Cardiol. 1985 Feb;17(2):145-52 - PubMed
  5. Am J Physiol. 1987 Sep;253(3 Pt 2):H709-11 - PubMed
  6. J Thorac Cardiovasc Surg. 1980 Oct;80(4):506-16 - PubMed
  7. Cardiovasc Res. 1984 Sep;18(9):528-37 - PubMed
  8. Circulation. 1994 Apr;89(4):1792-801 - PubMed
  9. Am J Physiol. 1987 Feb;252(2 Pt 2):H368-73 - PubMed
  10. Eur Heart J. 1988 Dec;9 Suppl N:34-9 - PubMed
  11. J Med Chem. 1994 Oct 28;37(22):3844-9 - PubMed
  12. J Thorac Cardiovasc Surg. 1995 Aug;110(2):328-39 - PubMed
  13. Circ Res. 1981 Oct;49(4):892-900 - PubMed
  14. Am J Cardiol. 1979 Nov;44(6):1115-21 - PubMed
  15. J Biol Chem. 1988 Jan 25;263(3):1353-7 - PubMed
  16. J Card Surg. 1994 May;9(3 Suppl):387-96 - PubMed
  17. J Cardiovasc Pharmacol. 1987 Aug;10(2):213-21 - PubMed
  18. Circulation. 1987 Jun;75(6):1295-309 - PubMed
  19. J Mol Cell Cardiol. 1989 Jul;21(7):691-5 - PubMed
  20. Acta Physiol Scand Suppl. 1986;548:39-46 - PubMed
  21. Circulation. 1993 Nov;88(5 Pt 2):II336-43 - PubMed
  22. Circulation. 1990 Nov;82(5 Suppl):IV341-50 - PubMed
  23. Biochem Pharmacol. 1982 Feb 15;31(4):535-9 - PubMed
  24. Ann N Y Acad Sci. 1988;522:433-53 - PubMed
  25. Circulation. 1988 Nov;78(5 Pt 2):III224-35 - PubMed
  26. Circulation. 1993 Nov;88(5 Pt 1):2359-69 - PubMed
  27. J Pharmacol Exp Ther. 1994 Jan;268(1):90-6 - PubMed
  28. J Card Surg. 1993 Mar;8(2 Suppl):257-61 - PubMed
  29. Am J Cardiol. 1977 Jun;39(7):986-93 - PubMed
  30. J Mol Cell Cardiol. 1988 May;20(5):443-56 - PubMed
  31. J Thorac Cardiovasc Surg. 1990 Sep;100(3):445-54 - PubMed
  32. Circulation. 1991 Jul;84(1):350-6 - PubMed
  33. Cardiovasc Res. 1987 May;21(5):328-36 - PubMed
  34. Am J Physiol. 1992 Nov;263(5 Pt 2):H1460-5 - PubMed
  35. Am J Cardiol. 1979 Jan;43(1):52-8 - PubMed
  36. Basic Res Cardiol. 1993 Nov-Dec;88(6):576-93 - PubMed
  37. Cardiovasc Res. 1993 Apr;27(4):669-73 - PubMed
  38. J Thorac Cardiovasc Surg. 1985 Oct;90(4):549-56 - PubMed
  39. Basic Res Cardiol. 1987 Sep-Oct;82(5):486-92 - PubMed
  40. Cardiovasc Res. 1985 Nov;19(11):686-92 - PubMed
  41. Circulation. 1985 May;71(5):994-1009 - PubMed
  42. Circulation. 1989 Nov;80(5):1400-11 - PubMed
  43. J Biol Chem. 1951 Nov;193(1):265-75 - PubMed
  44. Circulation. 1981 Oct;64(4):796-807 - PubMed
  45. Circulation. 1991 May;83(5):1499-509 - PubMed
  46. Am J Physiol. 1992 Aug;263(2 Pt 2):H552-8 - PubMed
  47. Am J Physiol. 1989 Dec;257(6 Pt 2):H1952-7 - PubMed
  48. J Cardiovasc Pharmacol. 1989 Jun;13(6):895-901 - PubMed
  49. Cardiovasc Res. 1988 Sep;22(9):674-8 - PubMed
  50. Am J Physiol. 1990 Jun;258(6 Pt 2):H1642-9 - PubMed

Substances

MeSH terms

Publication Types

Grant support