Summary
THE clinical, pharmacodynamic and haemodynamic effects of combined alpha and beta-blockade induced by the intravenous infusion of labetalol were evaluated in 32 patients with uncomplicated acute myocardial infarction admitted to a coronary care unit. Labetalol infusion induced linear dose-related falls in systemic blood pressure, and a quadratic reduction in cardiac output; heart rate and left heart filling pressure were unchanged. There was a linear reduction in calculated systemic vascular resistance. The pharmacodynamic activity of the drug was closely correlated with the plasma concentration; differences in patient sensitivity resulted in the absence of any simple relationship between pharmacodynamic activity and cumulative intravenous dosage.
These studies demonstrate that balanced alpha and beta-blockade with labetalol in patients immediately following infarction favourably affects some of the major determinants of myocardial oxygen consumption without producing undue depression of left ventricular performance. They also demonstrate the haemodynamic safety of labetalol; however individual patient dose-titration against blood pressure is mandatory if continuous intravenous infusion of the drug is contemplated.
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Bay, G., Lund, Larsen, P., Lorentsen, E., Silvertsen E. 1967. Haemodynamic effect of propranolol in acute myocardial infarction. Br. Med. J. i, 141.
Biomedical Computer Program — ‘P’ Series. Eds.: W. J. Dixon, M. B. Brown, 1979. Berkely, University of California Press, pp. 540–88.
Chiariello, M., Brevetti, G., De Rosa, G.et al. 1980. Protective effects of simultaneous alpha-and beta-adrenergic receptor blockade on myocardial cell necrosis after coronary arterial occlusion in rats. Am. J. Cardiol. 46, 249.
Corr, P. B., Clarke, G. and Pogwizd, S. 1981. Influences of labetalol, a combined alpha-and beta-adrenergic receptor blocking agent in ischaemic and reperfused myocardium. Circulation 64 (4), 97.
Dietmar, H., Glogar, R., Kloner, R. A. 1981. Reduction of myocardial ischaemia by balanced alpha-and beta-blockade with labetalol. Am. J. Cardiol. (Abst.) 47, 430.
Gold, H. K., Leinbach, R. C., Maroko, P. R. 1976. Propranolol induced reduction of signs of ischaemic injury during acute myocardial infarction. Am. J. Cardiol. 38, 689.
Hjalmarson, A., Elmfeldt, D., Herlitz, J.et al. 1981. Effect on mortality of metoprolol in acute myocardial infarction. Lancet ii, 823.
Jewitt, D. E., Burgess, P. A., Shillingford, J. P. 1970. The circulatory effects of practolol in patients with acute myocardial infarction. Cardiovasc. Res. 4, 188.
Libby, P., Maroko, P. R., Covell, J. W., Malloch, C. I., Ross, J. Jr., Braunwald, E. 1971. The effects of practolol on left ventricular function and infarct size following acute experimental coronary occlusion. Clin. Res. 19, 116.
Majid, P. A., Sharma, B., Taylor, S. H. 1971. Phentolamine for vasodilator treatment of severe heart failure. Lancet ii, 719.
Maroko, P. R., Kjekshus, J. K., Sobel, B. E.et al. 1971. Factors influencing infarct size following experimental coronary artery occlusions. Circulation 43, 67.
Marx, P. G., Reid, D. S. 1979. Labetalol infusion in acute myocardial infarction with systemic hypertension. Br. J. Clin. Pharmacol. 8, 233S.
Mueller, H., Ayres, S. M. 1976. Propranolol in acute myocardial infarction in man; effect on haemodynamics and myocardial oxygenation. Post Grad. Med. J. 52 (Suppl. 4), 141.
Norris, R. M., Samell, N. L., Clarke, E. D., Smith, W. M., Williams, B. 1978. Protective effect of propranolol in threatened myocardial infarction. Lancet ii, 907.
Pelides, L. J., Reid, D. W., Thomas, M., Shillingford, J. P. 1972. Inhibition by beta-blockade of the ST segment elevation after acute myocardial infarction in man. Cardiovasc. Res. 6, 295.
Peter, T., Norris, R. M., Clarke, E. D.et al. 1978. Reduction of enzyme levels by propranolol after acute myocardial infarction. Circulation 57, 1091.
Reid, D. S., Pelides, L. J., Shillingford, J. P., Thomas, M. 1976. Electrocardiographic surface mapping of the heart following myocardial infarction and the influence of beta-blockade. Post Grad. Med. J. 52 (Suppl. 4), 135.
Richards, D. A., Maconochie, J. G., Bland, R. E., Hopkins, R., Woodings, E. P., Martin, L. E. 1977. Relationship between plasma concentrations and pharmacological effects of labetalol. Eur. J. Clin. Pharmacol. 2, 85.
Richards, D. A., Prichard, B. N. C., Dobbs, R. J. 1978. Adrenoceptor blockade of the circulatory responses to intravenous isoproterenol. Clin. Pharmacol. Therapeut. 24, 264.
Sheridan, D. J., Penkoske, P. A., Sobel, B. E., Corr, P. B. 1980. Alpha-adrenergic contributions to dysrhythmias during myocardial ischaemia and reperfusion in the cat. J. Clin. Invest. 65, 161.
Silke, B., Nelson, G. I. C., Ahuja, R. C., Taylor, S. H. 1982. Comparative haemodynamic doseresponse effects of propranolol and labetalol in coronary heart disease. Br. Heart J. 48, 364–71.
Taylor, S. H., Silke, B., Nelson, G. I. C., Okoli, R. C., Ahuja, R. C. 1982. Haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone in patients with coronary heart disease. Br. Med. J. 285, 325.
Taylor, S. H., Silke, B., Ebbutt, A., Sutton, G. C., Prout, B. J. and Burley, D. M. 1982. A long-term prevention study with oxprenolol in coronary heart disease. N. Engl. J. Med. 307, 1293.
Timmis, A. D., Fowler, M. B., Jaggaro, N. S. V., Chamberlain, D. A. 1980. Labetalol infusion for the treatment of hypertension in acute myocardial infarction. Eur. Heart J. 1, 413.
Yusuf, S., Ramsdale, D., Peto, R.et al. 1980. Early intravenous atenolol treatment in suspected acute myocardial infarction. Lancet ii, 273.
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Silke, B., Nelson, G.I.C., Ahuja, R.C. et al. Pharmacokinetic and haemodynamic studies with labetalol in acute myocardial infarction. Ir J Med Sci 152, 179–186 (1983). https://doi.org/10.1007/BF02954714
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DOI: https://doi.org/10.1007/BF02954714