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Comparative study of the effects of acebutolol, atenolol, d-propranolol and dl,-propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: A 31P NMR study on the isolated rat heart

  • Ischemia and Reperfusion
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Summary

31-P NMR spectroscopy data recorded for the isolated heart were analyzed, in conjunction with functional and biochemical variables, in order to investigate the effect observed for several different beta-adrenoceptor antagonists on the alterations provoked by global partial ischemia (37°C, 24 minutes, 1% residual coronary flow) and reperfusion in the metabolism of the myocardium. During ischemia: intracellular acidosis, adenosine triphosphate (ATP) degradation, and inorganic phosphate (Pi) accumulation were found to be reduced whether the perfusion fluid contained: acebutolol 2.7×10-5 M, atenolol 10-5 M, d-propranolol 10-5 M, or dl-propranolol 10-5 M. On reperfusion metabolic and functional variables were variously affected by the different drugs, except the Pi level which was, in all series, significantly lower compared with control hearts. The adenylate charge and the glycogen stores were protected in the acebutolol, dl-propranolol, and d-propranolol groups. The ATP level was higher than in controls only in the acebutolol and atenolol groups. The intracellular pH recovered to values non-significantly different from preischemic values in the acebutolol and dl-propranol-treated hearts only. The mechanical performance, expressed as the rate-pressure product, was unaltered by the ischemia-reperfusion sequence in the acebutolol and d-propranolol series, while decreasing significantly in controls and in the atenolol group. In dl-propranolol-treated hearts the mechanical activity, which in normoxic conditions was already halved during the effect of the drug, remained at this same level after ischemia. From these observations, it appears that the nonspecific properties of the drugs, as distinct from beta-blockade, play an important part in attenuating the ischemia-induced alteration in myocardial metabolism. Thus, it can be postulated that (1) the metabolic effects of dl-propranolol probably result largely from the reduction of heart work induced by this drug; (2) the maintenance of energy metabolism associated with the preservation of the myocardial activity, as observed in the case of acebutolol and d-propranolol, is possibly a consequence of the existence of a membrane-stabilizing activity.

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Authors and Affiliations

  1. Laboratoire de Physiologie Cellulaire Cardiaque (URA CNRS 56), Université Joseph Fourier, Grenoble, France

    N. Lavanchy & A. Rossi

  2. Groupe RMBM, Service de Physique, DRF, Centre d'Etudes Nucléaires de Grenoble, Grenoble, France

    J. Martin

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  1. N. Lavanchy
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  2. J. Martin
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  3. A. Rossi
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Lavanchy, N., Martin, J. & Rossi, A. Comparative study of the effects of acebutolol, atenolol, d-propranolol and dl,-propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: A 31P NMR study on the isolated rat heart. Cardiovasc Drug Ther 2, 501–512 (1988). https://doi.org/10.1007/BF00051189

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