Abstract
In this study, we have investigated the importance of partial agonist activity during myocardial ischemia by comparing the effects of equiblocking doses of Oxprenolol, which possesses partial agonist activity, to propranolol which does not. In the isolated, globally ischemic (low-flow) rat heart, when propranolol or Oxprenolol was added alone during the ischemic period, only propranolol reduced enzyme leakage relative to control. However, when the hearts were perfused (10 min) prior to ischemia with these drugs, both ß blockers caused a significant reduction in enzyme leakage. Under conditions of enhanced sympathetic drive (in the presence of 0.01 |xm isoproterenol), both ß blockers reduced enzyme leakage to differing extents. In hearts with low sympathetic drive (reserpine pretreatment), enzyme leakage was unaffected by propranolol and exacerbated by Oxprenolol. The results of this study suggest that Oxprenolol and propranolol influence ischemic damage to differing extents and that this difference is due to partial agonist activity. Also, the protective action of all ß-blocking compounds depends greatly on the background level of sympathetic drive.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
De Leins, J., Peyrot, M., and Feuvray, D. 1978. Pharmacological reduction of ischaemia-induced enzyme release from isolated rat hearts. J. Mol. Med. 3:111–121.
Dhalla, N. S., Lee, S. L., Anand, M. B., and Chauhan, M. S. 1977. Effects of acebutolol, practolol and propranolol on the rat heart sarcolemma. Biochem. Pharmacol. 26:2055–2060.
Hearse, D. J., Garlick, P. B., Humphrey, S. M., and Shillingford, J. P. 1978. The effect of drugs on enzyme release from the hypoxic myocardium. Eur. J. Cardiol. 7:421–436.
Hearse, D. J., Humphrey, S. M., and Bullock, G. R. 1978. The oxygen paradox and the calcium paradox: Two facets of the same problem? J. Mol. Cel. Cardiol. 10:641–668.
Kloner, R., Fishbein, M., Braunwald, E., and Maroko, P. 1977. Effect of propranolol on mitochondrial morphology during acute myocardial ischemia. Am. J. Cardiol. 55:872–886.
Krebs, H. A., and Henseleit, K. 1932. Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe Seylers Z. Physiol. Chem. 210:33–66.
Manning, A. S., Hearse, D. J., Dennis, S. C, Bullock, G. R., and Coltart, D. J. 1980. Myocardial ischaemia: An isolated, globally perfused rat heart model for metabolic and pharmacological studies. Eur. J. Cardiol. 11:1–21.
Maroko, P. R., Kjekshus, J. K., Sobel, B. E., Watanabe, T., Covell, J. W., Ross, J., and Braunwald, E. 1971. Factors influencing infarct size following experimental coronary artery occlusions. Circulation 43:67–82.
Marshall, R. J., and Parratt, J. R. 1976. Comparative effects of propranolol and practolol in the early stages of experimental canine myocardial infarction. Br. J. Pharmacol. 57:295–303.
Nayler, W., Grau, A., and Yepez, C. 1977. Beta-adrenoceptor antagonists and the release of creatine Phosphokinase from hypoxic heart muscle. Cardiovasc. Res. 11:344–352.
Oliver, J. 1965. A spectrophotometry method for the determination of creatine Phosphokinase and myokinase. Biochem. J. 61:116–122.
Reimer, K., Rasmussen, M., and Jennings, R. 1973. Reduction by propranolol of myocardial necrosis following temporary coronary artery occlusion in dogs. Circ. Res. 33:353–363.
Scott, E., Truog, A., Rogg, H., and Meier, M. 1979. Effect of propranolol during different degrees of hypoxia in the isolated guinea-pig heart. J. Mol. Cell. Cardiol. 11(Suppl. 2):54.
Serano, P. A., Chavez-Lara, B., Bisteni, A., and Sodi-Pallares, D. 1971. Effect of propranolol on catecholamine content of injured cardiac tissue. J. Mol. Cell Cardiol. 2:91–97.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1983 Springer Science+Business Media New York
About this chapter
Cite this chapter
Manning, A.S., Keogh, J.M., Coltart, D.J., Hearse, D.J. (1983). The Effects of β Blockade and Partial Agonist Activity during Myocardial Ischemia. In: Chazov, E., Saks, V., Rona, G. (eds) Advances in Myocardiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4441-5_49
Download citation
DOI: https://doi.org/10.1007/978-1-4757-4441-5_49
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-4443-9
Online ISBN: 978-1-4757-4441-5
eBook Packages: Springer Book Archive