Skip to main content
SpringerLink
Log in

Normothermic ischemic cardiac arrest in the isolated working rabbit heart: Effects of dl-nebivolol and atenolol

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

The effect of pretreatment with selective β1-adrenoceptor blockers (dl-nebivolol or atenolol) on myocardial mechanical activity, mitochondrial function, morphology, and calcium cytochemistry was studied during normothermic ischemic arrest and reperfusion of isolated working rabbit hearts. The hearts subjected to 25 min of ischemia followed by 30 min of post-ischemic reperfusion showed typical signs of severe myocardial ischemic damage. The ultrastructural changes showed a good relation with the changes in mechanical activity and mitochondrial function. To determine whether these changes could be prevented or reduced by β1-adrenoceptor blockade, dl-nebivolol or atenolol (0.62 mg/liter) was added to the perfusate 30 min before the induction of ischemia. The results showed that dl-nebivolol exerted a protective effect on recovery of mechanical activity, on mitochondrial function during reperfusion as well as on the ultrastructure as examined at the end of the reperfusion period. On the other hand, atenolol failed to protect the myocardium against ischemia-reperfusion damage in the isolated working rabbit heart.

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. Bhajana V, Alto LE, Dhalla NS (1980) The effects of β-adrenergic receptor blockers on heart mitochondrial metabolism. Gen Pharmacol 11:271–274

    Google Scholar 

  2. Borgers M, Liu GS, Xhonneux R, Thoné F, Van Overloop P (1987) Changes in ultrastructure and calcium distribution in the isolated working rabbit heart after ischemia. Am J Pathol 126:92–102

    Google Scholar 

  3. Borgers M, Thoné F, Verheyen A, Ter Keurs HEDJ (1984) Localization of calcium in skeletal and cardiac muscle. Histochem J 16:295–309

    Google Scholar 

  4. Brachfield N (1976) Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. Am J Cardiol 37:528–532

    Google Scholar 

  5. Bush LR, Li YP, Shlafer M, Jolly SR, Lucchesi BR (1981) Protective effects of diltiazem during myocardial ischemia in isolated cat heart. J Pharmacol Exp Ther 218:653–661

    Google Scholar 

  6. Dhalla NS, Lee SL (1976) Comparison of the action of acebutolol, propranolol and practolol on calcium transport by heart microsomes and mitochondria. Br J Pharmacol 57:215–221

    Google Scholar 

  7. Dhalla NS, Lee SL, Anand MB, Chauhan MS (1977) Effects of acebutolol, practolol and propranolol on the rat heart sarcolemma. Biochem Pharmacol 26:2055–2060

    Google Scholar 

  8. Dhalla NS, Pangia V, Singal PK, Makino N, Dixon IMC, Eyolfson DA (1988) Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury. J Mol Cell Cardiol 20 (suppl 11):3–13

    Google Scholar 

  9. Edoute Y, Graney D, Sanan D, Kotze JCN, Lochner A (1982) Normothermic ischemic cardiac arrest of isolated working rat heart: effects of reserpine and propranolol on functional, metabolic and morphological recovery. Cardiovasc Res 16:428–438

    Google Scholar 

  10. Hearse DJ, Garlick PB, Humphrey SM (1977) Ischemic contracture of the myocardium: mechanisms and prevention. Am J Cardiol 39:987–993

    Google Scholar 

  11. Jennings RB, Ganote CE (1976) Mitochondrial structure and function in acute myocardial ischemic injury. Circ Res (suppl I) 38 (5):80–91

    Google Scholar 

  12. Jennings RB, Reimer KA (1981) Lethal myocardial ischemic injury. Am J Pathol 102:241–255

    Google Scholar 

  13. Jennings RB, Reimer KA, Steenbergen C (1986) Myocardial ischemia revised. The osmolar load, membrane damage and reperfusion. J Mol Cell Cardiol 18:769–780

    Google Scholar 

  14. Kirkels JH, Ruigrok TJC, Van Echteld CJA, Meijler F (1988) Protective effect of pretreatment with the calcium antagonist anipamil on the ischemic-reperfused rat myocardium: a phosphorus-31 nuclear magnetic resonance study. J Am Cell Cardiol 11:1087–1093

    Google Scholar 

  15. Kloner RA, Fishbein MC, Braunwald E, Maroko PR (1978) Effect of propranolol on mitochondrial morphology during acute myocardial ischemia. Am J Cardiol 41:880–886

    Google Scholar 

  16. Liu GS, Borgers M, Xhonneux R, Van Overloop P, Thoné F, Wouters L, Leijssen L (1986) Evaluation of protective effects of lidoflazine and mioflazine in cardiac ischemia. Drug Dev Res 8:407–416

    Google Scholar 

  17. Lu HR, Vandeplassche G, Wouters L, Borgers M (1989) β-blockade in the ischemic reperfused working rabbit heart: dissociation of β-adrenergic blocking and protective effects. Arch Int Pharmacodyn Ther 301:165–181

    Google Scholar 

  18. Lu HR, Vandeplassche G, Wouters L, Flameng W, Borgers M (1989) Effects of β-adrenergic antagonists on mitochondrial and cardiodynamic function in ischemic reperfused myocardium of the isolated working rabbit heart. Eur J Pharmacol (1990 in press)

  19. Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Coveel JW, Braunwald W (1971) Factors influencing infarct size following experimental coronary occlusions. Circulation 43:67–82

    Google Scholar 

  20. Nakamura K, Ichihara K, Abiko Y (1989) Effect of propranolol on accumulation of NEFA in the ischemic perfused rat heart. Eur J Pharmacol 160:61–69

    Google Scholar 

  21. Nayler WG, Ferrari R, Williams A (1980) Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol 46:242–248

    Google Scholar 

  22. Nayler WG, Panagiotopoulos S, Elz JS, Oaly MJ (1988) Calcium-mediated damage during postischemic reperfusion. J Mol Cell Cardiol (suppl 1):41–54

  23. Nayler WG, Stone J, Carson V (1969) The effects of β-adrenergic antagonists on cardiac contractions, myofibrillar ATPase activity, high energy phosphate stores and lipid facilitated transport of calcium ions. J Pharmacol Exp Ther 165:225–233

    Google Scholar 

  24. Neely JR, Liebermeister H, Battersby EJ, Morgan HE (1967) Effects of pressure development on oxygen consumption by the isolated rat heart. Am J Physiol 212:804–816

    Google Scholar 

  25. Ochi S, Ogawa Y, Imai H, Nakazawa M, Imai S (1988) Effects of β-blockers on the fall of pH in the early phase of ischemia in the isolated perfused rat heart: a nuclear magnetic resonance study. J Cardiovasc Pharmacol 11:326–331

    Google Scholar 

  26. Piper HM, Sezer O, Schleyer M, Schwartz P, Hütter JF, Spieckermann PG (1985) Development of ischemia-induced damage in defined mitochondrial subpopulations. J Mol Cell Cardiol 17:885–896

    Google Scholar 

  27. Reimer KA, Rasmussen MM, Jennings RB (1973) Reduction by propranolol of myocardial necrosis following temporary coronary artery occlusion in dogs. Circ Res 33:353–363

    Google Scholar 

  28. Van de Water A, Janssens W, Van Nueten J, Xhonneux R, De Cree J, Verhaegen H, Reneman RS, Janssen PAJ (1988) Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent and selective beta1-adrenergic antagonist. J Cardiovasc Pharmacol 11:552–562

    Google Scholar 

  29. Von Korff RCO (1965) Metabolic characteristics of isolated rabbit heart mitochondria. J Biol Chem 240:1351–1358

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Pharmacology, Janssen Research Foundation, 2340, Beerse, Belgium

    G. Vandeplassche, H. R. Lu, L. Wouters & M. Borgers

  2. The Department of Cardiovascular Surgery, Catholic University of Leuven, Belgium

    W. Flameng

Authors
  1. G. Vandeplassche
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. R. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Wouters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Flameng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Borgers
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vandeplassche, G., Lu, H.R., Wouters, L. et al. Normothermic ischemic cardiac arrest in the isolated working rabbit heart: Effects of dl-nebivolol and atenolol. Basic Res Cardiol 86, 21–31 (1991). https://doi.org/10.1007/BF02193868

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02193868

Key words

Search

Navigation