British journal of clinical pharmacology
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Br J Clin Pharmacol · Jun 1982
Clinical Trial Controlled Clinical TrialEffects of combined alpha- and beta-blockade by labetalol in patients with coronary artery disease.
1 The effect of labetalol 100 mg orally twice daily on exercise tolerance has been compared with placebo in 19 normotensive subjects with angiographic evidence of coronary artery disease. 2 Labetalol, at the same work load as during placebo exercise, significantly reduced systolic and diastolic blood pressures, as well as heart rate and rate-pressure product. 3 Similarly, ST segment depression was reduced by labetalol from 2.0 +/- 0.4 to 1.36 +/- 0.6 mm (P less than 0.001), thus enabling an increase in exercise tolerance from a control value of 83.7 +/- 18 to 95.3 +/- 19 W (P less than 0.005). 4 In seven other patients, also with coronary artery disease, the haemodynamic effects of a single 0.6 mg/kg intravenous dose of the drug was evaluated during exercise. 5 Compared with conditions during control exercise, labetalol induced a significant reduction in rate-pressure product from 17228 +/- 2375 to 13445 +/- 2404 mmHg/min (P less than 0.005) and in peripheral vascular resistance from 612.0 +/- 61.2 to 512.7 +/- 36.2 dyn cm-5 m-2 (P less than 0.0025). These events were not accompanied by any change in cardiac index and in dP/dT left ventricular end-diastolic pressure (LVEDP) ratio. 6 These data suggest that labetalol may induce reduction in myocardial oxygen consumption, thereby increasing exercise tolerance in patients with coronary artery disease, without impairment of left ventricular performance.
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1 Observed and possible roles for the use of labetalol in anaesthesia are reviewed. 2 When used together with halothane inhalation anaesthesia, satisfactory conditions are achieved for safe hypotensive anaesthesia: (a) Labetalol and halothane have additive hypotensive effects. (b) The usual dose of labetalol is 25 mg intravenously together with 1% halothane. (c) The duration of hypotension can be controlled in the presence of halothane; withdrawal leads to rapid recovery of pre-surgery blood pressure. (d) High doses of halothane (3%) with labetalol predispose to the myocardial depressant effects of halothane and undesirable reductions in myocardial performance. 3 As it is now seen to be important to reduce the blood pressure before anaesthesia and surgery in hypertensive patients, then labetalol is likely to be satisfactory either by the intravenous route for immediate reduction or for less urgent reduction of raised arterial pressure by the oral route. 4 It is known that anaesthesia (for example, laryngoscopy) and surgery provoke hypertensive responses which are particularly undesirable in the patient with pre-existent myocardial ischaemia. In such cases it is likely that previous treatment with labetalol will satisfactorily modify unwanted hypertensive and cardiovascular responses.