Therapy and prevention

Many vasodilators have been tried as antianginal agents, but the reflex increase in sympathetic tone produced by these drugs necessitate their use with caution in patients with angina. In the first part of this study, captopril was given to 14 patients with angina and systolic arterial pressures of greater than 120 mm Hg. Over the short term, captopril decreased arterial blood pressure (from 110 + 18 to 98 18 mm Hg, p < .01) without increasing heart rate (75 + 15 vs 74 ± 15 beats/min), arterial concentrations of epinephrine (0.38 ± 0.28 vs 0.34 ± 0.25 nM) or norepinephrine (2.7 ± 2.1 vs 2.8 ± 2.1 nM), or transmyocardial norepinephrine balance (216 254 vs 146 170 p mol/min). Captopril decreased average myocardial oxygen consumption (9.7 4.1 to 8.2 2.7 ml/min, p < .01). Given over the long term (mean 5.5 months), captopril decreased the severity of angina from NYHA classification 3.0 ± 0.8 to 1.6 0.8. In the second part of this study, captopril was given in a prospective, randomized, double-blind, placebo-controlled study to 21 patients with stable exerciseinduced angina and systolic arterial pressures greater than 120 mm Hg. Captopril increased exercise time (309 ± 137 vs 374 + 142 sec, p < .05) without changing anginal threshold (rate-pressure product 17.0 ± 6.0 vs 17.1 ± 5.6 x 10-3). We conclude that captopril decreases mean arterial pressure without causing a reflex increase in myocardial sympathetic tone. By decreasing myocardial oxygen consumption, captopril may prove to be a useful adjunct to the antianginal drug regimens of patients with systolic arterial pressures greater than 120 mm Hg. Circulation 71, No. 2, 317-325, 1985. MOST VASODILATORS decrease arterial pressure and thus myocardial work, but their antianginal efficacy is limited by reflex tachycardia.' 2 Use of captopril has the advantage that it does not cause reflex tachycardia and in previous work we have shown that the drug decreased myocardial oxygen consumption when given to patients with congestive heart failure and coronary artery disease.3 We have recently shown that captopril decreases myocardial oxygen consumption when given to hypertensive patients with coronary artery disease.4 These effects may be the result of decreased myocardial sympathetic tone.5'-2 If this is true, captopril might prove useful in the treatment of patients with coronary artery disease. To measure myocardial sympathetic activation in vivo in man, it is important to measure arterial concenFrom the University Clinics and the Department of Medicine of the Montreal General Hospital, McGill University, and from the Research Centre of Sacre-Coeur Hospital, Montreal, Quebec. Supported by the Department of Medicine of the Montreal General Hospital, the Medical Research Council of Canada, the Quebec Heart Foundation, and the Sacre-Coeur Hospital Foundation. Address for correspondence: Jean-Lucien Rouleau, M.D., Centre de Recherche, Hopital Sacre-Coeur, 5400 Blvd. Gouin ouest, Montreal, Quebec, Canada H4J 1C5. Received July 31, 1984; revision accepted Nov. 1, 1984. trations of epinephrine and norepinephrine and to measure myocardial norepinephrine balance (arterialcoronary sinus concentration times coronary sinus flow).13 Myocardial norepinephrine balance is the convergence of norepinephrine uptake and release in the heart and has been shown to more closely reflect myocardial sympathetic tone than levels of circulating catecholamines. 11 In this study, arterial and coronary sinus epinephrine and norepinephrine concentrations were measured before and after giving captopril to 14 patients with moderate-to-severe exercise-induced angina. Also, the effects of captopril on exercise-induced angina were assessed in a further 21 patients. Materials and methods Part I hemodynamic protocol. Fourteen patients (six women and eight men) with stable angina who responded poorly to treatment with calcium-entry blockers and with fl-blockers and nitrates were selected for the study. Exclusion criteria included creatinine level of greater than 2 mg/dl, proteinuria of greater than 1 g/day, or presence of any immunologic disease. To avoid induction of hypotension, only patients with systolic arterial pressures greater than 120 mm Hg were enrolled in the study. The patients ranged in age 48 to 79 years and had experienced angina for 4 months to 14 years. Five patients had sigVol. 71, No. 2, February 1985 317