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Postconditioning the Isolated Working Rat Heart

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Abstract

Purpose

Despite the attention focussed on postconditioning (postC; brief cycles of reperfusion/ischaemia at the onset of reperfusion, conferring cardioprotection against reperfusion injury), an infarct sparing effect for postC in the isolated working heart model has not been reported. The purpose of this study was to develop a cardioprotective postC protocol in this model.

Methods

Hearts from male Wistar rats (210–350 g) were perfused either retrogradely (Langendorff) or in the working mode. For functional studies 30 or 35 min global ischaemia (GI) and 20 or 25 min GI were applied in the Langendorff and working heart models respectively. Infarct size was measured after 35 min regional ischaemia (RI) in both models. In the latter studies hearts were subdivided into low (36.5°C) and high (37°C) temperature groups (during both ischaemia and initial reperfusion). In all groups hearts were either freely reperfused (nonPostC) or postconditioned (postC) by 6 × 10 s ischaemia/reperfusion cycles.

Results

In both perfusion modes postC only elicited an infarct sparing effect after a slight elevation in temperature to 37°C (Langendorff: L-nonPostC = 47.99 ± 3.31% vs. L-postC = 27.81 ± 2.49%, p < 0.0001; and work = W-nonPostC: 35.81 ± 3.67% vs. W-postC = 17.74 ± 2.72%, p < 0.001). However, only in the Langendorff group could postC conserve post-ischaemic function, while no significant recoveries were seen in the working hearts.

Conclusion

We demonstrated an infarct sparing effect for postC in the working heart model, which unlike the Langendorff model, was not associated with functional preservation. The infarct sparing effect of postC in both models was however extremely sensitive to even slight fluctuations in temperature.

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References

  1. Zhao Z-Q, Corvera JS, Halkos ME, Kerendi F, Wang N-P, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 2003;285:H579–88.

    PubMed  CAS  Google Scholar 

  2. Dow J, Kloner RA. Postconditioning does not reduce myocardial infarct size in an in vivo regional ischemia rodent model. J Cardiovasc Pharmacol Ther 2007;12:153–63. Jun.

    Article  PubMed  Google Scholar 

  3. Kaljusto ML, Mori T, Mohammad Husain Rizvi S, Galagudza M, Frantzen ML, Valen G, et al. Postconditioning in rats and mice. Scand Cardiovasc J 2006;40:334–41. Dec.

    Article  PubMed  Google Scholar 

  4. Vinten-Johansen J, Zhao Z-Q, Zatta AJ, Kin H, Halkos ME, Kerendi F. Postconditioning: a new link in nature’s armor against myocardial ischemia–reperfusion injury. Basic Res Cardiol 2005;100:295–310.

    Article  PubMed  CAS  Google Scholar 

  5. Sasaki H, Shimizu M, Ogawa K, Okazaki F, Taniguchi M, Taniguchi I, et al. Brief ischemia–reperfusion performed after prolonged ischemia (ischemic postconditioning) can terminate reperfusion arrhythmias with no reduction of cardiac function in rats. Int Heart J 2007;48:205–13.

    Article  PubMed  Google Scholar 

  6. Lauzier B, Sicard P, Bouchot O, Delemasure S, Menetrier F, Moreau D, et al. After four hours of cold ischemia and cardioplegic protocol, the heart can still be rescued with postconditioning. Transplantation 2007;84:1474–82.

    Article  PubMed  Google Scholar 

  7. Lochner A, Genade S, Moolman JA. Ischemic preconditioning: infarct size is a more reliable endpoint than functional recovery. Basic Res Cardiol 2003;98:337–46.

    Article  PubMed  CAS  Google Scholar 

  8. Jenkins DP, Pugsley WB, Yellon DM. Ischaemic preconditioning in a model of global ischaemia: infarct size limitation, but no reduction of stunning. J Mol Cell Cardiol 1995;27:1623–32.

    Article  PubMed  CAS  Google Scholar 

  9. Uematsu M, Okada M. Differences in prolonged ischemia length using ischemic preconditioning in the rabbit heart: tolerable limitation time for surgically induced myocardial ischemia during normothermic cardiac operation. J Cardiovasc Surg 2001;42:323–31.

    CAS  Google Scholar 

  10. Penna C, Cappello S, Mancardi D, Raimondo S, Rastaldo R, Gattullo D, et al. Post-conditioning reduces infarct size in the isolated rat heart: role of coronary flow and pressure and the nitric oxide/cGMP pathway. Basic Res Cardiol 2006;101:168–79.

    Article  PubMed  CAS  Google Scholar 

  11. Marais E, Genade S, Salie R, Huisamen B, Maritz S, Moolman JA, et al. The temporal relationship between p38 MAPK and HSP27 activation in ischaemic and pharmacological preconditioning. Basic Res Cardiol 2005;100:35–47.

    Article  PubMed  CAS  Google Scholar 

  12. Schwartz LM, Verbinski SG, Vander Heide RS, Reimer KA. Epicardial temperature is a major predictor of myocardial infarct size in dogs. J Mol Cell Cardiol 1997;29:1577–83.

    Article  PubMed  CAS  Google Scholar 

  13. Cohen MV, Yang X-M, Downey JM. Smaller infarct after preconditioning does not predict extent of early functional improvement of reperfused heart. Am J Physiol Heart Circ Physiol 1999;277:1754–61.

    Google Scholar 

  14. Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K. Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol 2005;289:H1618–26.

    Article  PubMed  CAS  Google Scholar 

  15. Yang X-C, Liu Y, Wang L-F, Cui L, Wang T, Ge Y-G, et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J Invasive Cardiol 2007;19:424–30.

    PubMed  Google Scholar 

  16. Taegtmeyer H, Hems R, Krebs HA. Utilization of energy-providing substrates in the isolated working rat heart. Biochem J 1980;186:701–11.

    PubMed  CAS  Google Scholar 

  17. Damerau W, Ibel J, Thürich T, Assadnazari H, Zimmer G. Generation of free radicals in Langendorff and working hearts during normoxia, hypoxia, and reoxygenation. Basic Res Cardiol 1993;88:141–9.

    PubMed  CAS  Google Scholar 

  18. Couvreur N, Lucats L, Tissier R, Bize A, Berdeaux A, Ghaleh B. Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits. Am J Physiol Heart Circ Physiol 2006;291:H1345–50.

    Article  PubMed  CAS  Google Scholar 

  19. Kin H, Zatta AJ, Lofye MT, Amerson BS, Halkos ME, Kerendi F, et al. Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res 2005;67:124–33.

    Article  PubMed  CAS  Google Scholar 

  20. Kin H, Zhao Z-Q, Sun H-Y, Wang N-P, Corvera JS, Halkos ME, et al. Postconditioning attenuates myocardial ischemia–reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 2004;62:74–85.

    Article  PubMed  CAS  Google Scholar 

  21. Tang X-L, Sato H, Tiwari S, Dawn B, Bi Q, Li Q, Shirk G, Bolli R. Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min. Am J Physiol Heart Circ Physiol 2006;291:H2308–17.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Derick van Vuuren was financially assisted by a scholarship from the National Research Foundation (NRF) of South Africa.

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Correspondence to Amanda Lochner.

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van Vuuren, D., Genis, A., Genade, S. et al. Postconditioning the Isolated Working Rat Heart. Cardiovasc Drugs Ther 22, 391–397 (2008). https://doi.org/10.1007/s10557-008-6119-6

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  • DOI: https://doi.org/10.1007/s10557-008-6119-6

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