Skip to main content
SpringerLink
Log in

N-2-mercaptopropionylglycine, a Scavanger of Reactive Oxygen Species, does not Modify the Early Antiarrhythmic Effect of Ischaemic Preconditioning in Anaesthetised Dogs

  • Basic Pharmacology
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Summary

Objective: The possible involvement of reactive oxygen species (ROS) in the protective effects of ischaemic preconditioning (PC) against arrhythmias was examined in anaesthetised dogs using the ROS scavenger N-2-mercaptopropionylglycine (MPG).

Methods: PC was induced in 20 chloralose-urethane anaesthetised dogs by two 5 min occlusions of the left anterior descending (LAD) coronary artery 20 min prior to the prolonged (25 min) ischaemia/reperfusion (I/R) insult. In 10 of these dogs MPG was infused locally into a small side branch of the LAD in a dose of 0.15 mg kg−1 min−1, starting 10 min prior to and continuing throughout the entire PC procedure. In another four dogs subjected to preconditioning in the absence and then 2h later in the presence of MPG free radical formation was evaluated by the chemiluminescence method. Eleven dogs, infused with saline and subjected to a 25 min I/R insult, served as controls. A further 9 dogs, which were not preconditioned, were given MPG over a period of 60 min prior to occlusion.

Results: Preconditioning markedly reduced the number of ventricular premature beats (VPBs; 86 ± 34 v. 377 ± 78; P < 0.05), the episodes of ventricular tachycardia (VT; 2.0 ± 0.7 v. 13.6 ± 4.5; P < 0.05) and the incidences of both VT (60% v. 91%) and ventricular fibrillation (0% v. 82%; P < 0.05) during the prolonged occlusion. Survival (from the combined ischaemia and reperfusion insult) was significantly increased (40% v. 0%; P < 0.05) by PC. MPG did not modify the protective effects of PC, although free radical (mostly superoxide) formation that occurred following PC was abrogated in the presence of MPG. Thus, the number of VPBs (111 ± 39), VT episodes (1.2 ± 0.9) and the incidences of VT (20%) and VF (0%) during occlusion were similar to the PC dogs. MPG itself did not significantly modify arrhythmia severity in non-PC dogs.

Conclusions: We conclude that in our canine model of ischaemia/reperfusion the generation of ROS does not play a trigger role in the early PC-induced antiarrhythmic protection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sun J-Z, Tang X-L, Park S-W, et al. Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious dogs. J Clin Invest 1996;97:562–576.

    Article  PubMed  CAS  Google Scholar 

  2. Kaeffer N, Richard V, Thuillez C. Delayed coronary endothelial protection 24 hours after preconditioning. Role of free radicals. Circulation 1997;96:2311–2316.

    PubMed  CAS  Google Scholar 

  3. Yamashita N, Hoshida S, Taniguchi N, et al. A “Second Window of Protection” occurs 24~h after ischemic preconditioning in the rat heart. J Mol Cell Cardiol1998;30:1181–1189.

    PubMed  CAS  Google Scholar 

  4. Tang X-L, Takano H, Rizvi A, et al. Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits. Am J Physiol, 2002;282:H281–H291.

    CAS  PubMed  Google Scholar 

  5. Yamashita N, Hoshida S, Otsu K, et al. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med1999;189:1699– 1706.

    PubMed  CAS  Google Scholar 

  6. Pain T, Yang X-M, Critz SD, et al. Opening of mitochondrial K ATP channels triggers the preconditioned state by generating free radicals. Circ Res 2000;87:460–466.

    PubMed  CAS  Google Scholar 

  7. Cohen MV, Yang X-M, Liu GS, et al. Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial K ATP channels. Circ Res 2001; 89:273–278.

    PubMed  CAS  Google Scholar 

  8. Hoshida S, Yamashita N, Otsu K, Hori M. The importance of manganese superoxide dismutase in delayed preconditioning: Involvement of reactive oxygen species and cytokines. Cardiovasc Res 2002;55:495–505.

    PubMed  CAS  Google Scholar 

  9. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation1986;74:1124–1136.

    PubMed  CAS  Google Scholar 

  10. Tanaka M, Fujiwara H, Yamasaki K, Sasayama S. Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischaemic preconditioning in the rabbit. Cardiovasc Res 1994;28:980–986.

    PubMed  CAS  Google Scholar 

  11. Iwamoto T, Miura T, Adachi T, et al. Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit. Circulation 1991;83:1015–1022.

    PubMed  CAS  Google Scholar 

  12. Richard V, Tron C, Thuillez C. Ischaemic preconditioning is not mediated by oxygen derived free radicals in rats. Cardiovasc Res1993;27:2016–2021.

    PubMed  CAS  Google Scholar 

  13. Shirato C, Miura T, Ooiwa H, et al. Tetrazolium artifactually indicates superoxide dismutase-induced salvage in reperfused rabbit heart. J Mol Cell Cardiol 1989;21:1187– 1193.

    PubMed  CAS  Google Scholar 

  14. Baines CP, Goto M., Downey JM. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol 1997;29:207–216.

    PubMed  CAS  Google Scholar 

  15. Liem DA, van den Doel MA, de Zeeuw S, et al. Role of adenosine in ischemic preconditioning in rats depends critically on the duration of the stimulus and involves both A(1) and A(3) receptors. Cardiovasc Res 2001;51:701–708.

    PubMed  CAS  Google Scholar 

  16. Liem DA, te Lintel Hekkert M, Mannintveld OC, et al. Myocardium tolerant to an adenosine-dependent ischemic preconditioning stimulus can still be protected by stimuli that employ alternative signaling pathways. Am J Physiol Heart Circ Physiol 2004 in press.

  17. Komori S, Fukimaki S, Ijili H, et al. Inhibitory effect of ischaemic preconditioning on ischemic arrhythmias using a rat coronary artery ligation model. Jpn J Electrocardiol 1990;10:774–782.

    Google Scholar 

  18. Végh Á, Szekeres L, Parratt JR. Protective effects of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products. Cardiovasc Res1990;24:1020–1023.

    PubMed  Google Scholar 

  19. Végh Á, Komori S, Szekeres L, Parratt JR. Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. Cardiovasc Res 1992;26:487–495.

    PubMed  Google Scholar 

  20. Shiki K, Hearse DJ. Preconditioning of ischemic myocardium: Reperfusion-induced arrhythmias. Am J Physiol 1987;253:H1470–1476.

    PubMed  CAS  Google Scholar 

  21. Altuğ S, Demiryürek AT, Kane KA, Kanzik I. Evidence for the involvement of peroxinitrite in ischaemic preconditioning in rat isolated hearts. Br J Pharmacol 2000;130:125–131.

    PubMed  Google Scholar 

  22. Mitsos SE, Fantone JC, Gallagher KP, et al. Canine myocardial reperfusion injury: Protection by a free radical scavenger, N-2-mercaptopropionyl glicine. J Cardiovasc Pharmacol 1986;8:978–988.

    PubMed  CAS  Google Scholar 

  23. Cai M, Ogawa R. Effects of free radical scavengers, methylprednisolone, and ulinastatin on acute xanthine and xanthine oxidase-induced lung injury in rats. Circ Shock 1994;43:1–78.

    Google Scholar 

  24. Woodward B, Zakaria M. Effect of some free radical scavangers on reperfusion-induced arrhythmias. J Mol Cell Cardiol 1985;17:485–494.

    PubMed  CAS  Google Scholar 

  25. Bernier M, Hearse DJ, Manning S. Reperfusion-induced arrhythmias and oxygen derived free radicals: Studies with ‘anti-free radical‘ interventions and a free radical generating system in the isolated perfused hearts. Circ Res1986;58:331–340.

    PubMed  CAS  Google Scholar 

  26. Wainwright CL, Parratt JR. Failure of allopurinol and a spin trapping agent N-t-butyl-α -phenyl nitrone to modify significantly ischaemia and reperfusion-induced arrhythmias. Br J Pharmacol 1987;91:49–59.

    PubMed  Google Scholar 

  27. Walker MJA, Curtis MJ, Hearse DJ, et al. The Lambeth Conventions: Guidelines for the study of arrhythmias in ischaemia, infarction, and reperfusion. Cardiovasc Res 1988; 22:447–455.

    PubMed  CAS  Google Scholar 

  28. Kaszala K, Végh Á, Papp JG, Parratt JR. Time course of the protection against ischaemia and reperfusion-induced ventricular arrhythmias resulting from brief periods of cardiac pacing. J Mol Cell Cardiol 1996;28:2085–2095.

    PubMed  CAS  Google Scholar 

  29. Gyllenhammar H. Lucigenin chemiluminescence in the assessement of neutrophil superoxide production. J Immun Methods 1987;97:209–213.

    CAS  Google Scholar 

  30. Guarnieri C, Georgountzos A, Caldarera I, et al. Polyamines stimulate superoxide production in human neutrophils acivated by N-Met-Leu-Phe but not by phorbol myristate acetate. Biochem Biophys Acta 1987;930:135–139.

    PubMed  CAS  Google Scholar 

  31. Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Circ Res 1989;65:607–622.

    PubMed  CAS  Google Scholar 

  32. Connaughton M, Lawson CS, Hearse DJ. Ischaemic preconditioning and arrhythmias induced by ischaemia and reperfusion. In: Marber MS, Yellon DM, eds. Ischaemia, Preconditioning and Adaptation. Oxford: Bios Scientific Publisher, 1996;59–84.

    Google Scholar 

  33. Parratt JR, Végh Á, Kaszala K, Papp JGY. Suppression of life-threatening ventricular arrhythmias by brief periods of ischaemia and by cardiac pacing with particular reference to delayed myocardial protection. In: Marber MS, Yellon DM, Eds. Ischaemia, Preconditioning and Adaptation. Oxford: Bios Scientific Publisher, 1996;85–111.

    Google Scholar 

  34. Maroko PR, Kjekshus JK, Sobel BE, et al. Factors influencing infarct size following experimental coronary artery occlusions. Circulation 1971;43:67–74.

    PubMed  CAS  Google Scholar 

  35. Wit AL, Janse MJ. The Ventricular Arrhythmias of Ischemia and Infarction. Electrophysiological Mechanisms. Mount Kisco, NY: Futura Publishing Company, 1993.

    Google Scholar 

  36. Meesmann W. Early arrhythmias and primary ventricular fibrillation after myocardial ischaemia in relation to preexisting coronary collaterals. In: Parratt JR, ed. Early Arrhythmias Resulting from Myocardial Ischaemia. New York: Oxford University Press, 1982;93–112.

    Google Scholar 

  37. Babai L, Szigeti Zs, Parratt JR, Végh Á. Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: Possible involvement of nitric oxide. Clin Sci 2002;102:435–445.

    PubMed  CAS  Google Scholar 

  38. Végh Á, Papp JGy, Parratt JR. Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors. Br J Pharmacol 1994;113:1167–1172.

    PubMed  Google Scholar 

  39. Végh Á, Szekeres L, Parratt JR. Preconditioning of the ischaemic myocardium; involvement of the L-arginine—nitric oxide pathway. Br J Pharmacol1992;107:648–652.

    PubMed  Google Scholar 

  40. Yellon DM, Downey JM. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol Rev2003;83:113–1151.

    Google Scholar 

  41. Végh Á, Szekeres L, Parratt JR. Transient ischaemia induced by rapid cardiac pacing results in myocardial preconditioning. Cardiovasc Res 1991;25:1051–1053.

    Article  PubMed  Google Scholar 

  42. Herzberg RM, Rubio R, Berne RM. Coronary occlusion and embolisation effect on blood flow in adjacent arteries. Am J Physiol 1966;210:169–175.

    PubMed  CAS  Google Scholar 

  43. Khouri EM, Gregg DE, Lowensohn HS. Flow in the major branches of the left coronary artery during experimental coronary insufficiency in the unanaesthetised dog. Circ Res 1968;23:99–109.

    PubMed  CAS  Google Scholar 

  44. Feigl EO. Coronary physiology. Physiol Rev1983;63:1–205.

    PubMed  CAS  Google Scholar 

  45. Végh Á, Szekeres L, Parratt JR. Inhibition of nitric oxide production in anaesthetised dogs fails to modify work-induced increase in coronary blood flow. J Physiol (Lond.) 1992;452:16P.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, H-6701, Hungary

    Hajnal Ágnes, László Nagy, James R. Parratt, Julius Papp & Ágnes Végh Ph.D., D.Sc. (Prof. Dr.)

  2. Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Faculty of Medicine, University of Szeged, Dóm tér 12, P.O. Box 427, H-6701, Hungary

    Ágnes Végh Ph.D., D.Sc. (Prof. Dr.)

Authors
  1. Hajnal Ágnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. László Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James R. Parratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julius Papp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ágnes Végh Ph.D., D.Sc.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ágnes Végh Ph.D., D.Sc..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ágnes, H., Nagy, L., Parratt, J.R. et al. N-2-mercaptopropionylglycine, a Scavanger of Reactive Oxygen Species, does not Modify the Early Antiarrhythmic Effect of Ischaemic Preconditioning in Anaesthetised Dogs. Cardiovasc Drugs Ther 18, 449–459 (2004). https://doi.org/10.1007/s10557-004-6222-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-004-6222-2

Key Words

Search

Navigation