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Antianginal and haemodynamic effects of alpha 1-adrenoceptor blockade
Insights
Alpha 1-adrenoceptor blockade with indoramin improved exercise tolerance and reduced angina symptoms in patients with chronic stable angina. This demonstrates indoramin
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic stable angina reduces exercise tolerance.
- Beta-blockers and nitrates are standard treatments.
Purpose of the Study:
- To evaluate the effect of alpha 1-adrenoceptor blockade with indoramin on exercise tolerance in patients with chronic stable angina.
- To investigate the antianginal mechanism of indoramin.
Main Methods:
- Double-blind crossover study in 15 patients with chronic stable angina.
- Oral indoramin (25 mg TID) or placebo, with continued beta-blockers and nitrates.
- Intravenous indoramin (0.2 mg/kg) in 11 patients to assess hemodynamic effects during pacing.
Main Results:
- Oral indoramin increased exercise duration by 17% and oxygen consumption by 21%.
- ST segment depression during exercise was significantly attenuated.
- Intravenous indoramin prolonged pacing time to angina by 37% without affecting resting heart rate.
Conclusions:
- Alpha 1-adrenoceptor blockade with indoramin enhances exercise capacity and reduces angina in chronic stable angina patients.
- Indoramin demonstrates potential as an antianginal agent, possibly through improved hemodynamics.
Abstract:
We studied the effects of alpha 1-adrenoceptor blockade with indoramin on exercise tolerance in 15 patients with chronic stable angina using a double-blind crossover protocol. Thirteen patients had been receiving beta-adrenoceptor blocking drugs and nitrates. The therapy of these patients was continued unchanged throughout the study. Indoramin, in a dose of 25 mg three times daily, prolonged exercise duration by 17% (p less than 0.01) and increased oxygen consumption during exercise by 21% (p less than 0.01), while the maximal double product was unchanged. This increase in exercise capacity was associated with significant attenuation in ST segment depression during exercise. To investigate the mechanism of this antianginal effect, we studied the effects of indoramin (0.2 mg/kg i.v.) on coronary and systemic haemodynamics in a further 11 male patients with chronic stable angina who were receiving beta-adrenoceptor blocking drugs. Measurements were obtained during sinus rhythm and during atrial pacing from 100 beats/min, incremented by 20 beats/min at intervals of 3 min until the onset of angina. Indoramin had no effect on resting heart rate (64 +/- 2 vs. 67 +/- 2 beats/min), but did prolong pacing time to angina (7.4 +/- 0.7 vs. 5.4 +/- 0.5 min; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)