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Three randomized, placebo-controlled, crossover experimental designs were used to define a suitable interdose interval and to study the adequacy of once-daily administration for applications in preventive trials on manifest or latent ischemic patients. Suppression of exercise tachycardia was used as the major effect variable. All measurements were made at different intervals after the last dose when the healthy subjects had been treated for at least 1 wk. Reductions of exercise tachycardia were found 24 hr after the last dose for atenolol, metoprolol, penbutolol, pindolol, propranolol, sotalol, and timolol. Penbutolol and propranolol induced equal reduction of exercise tachycardia at the end of the dose interval regardless of whether the total daily dose was given once daily or divided in 2 daily doses. Atenolol and sotalol, both with long half-lifes (t1/2s), were not superior to other beta blockers. Neither were slow-release preparations of metoprolol and propranolol markedly more effective 24 hr after the preparation than after ordinary tablets. Plasma concentration-time patterns after slow-release preparations may be important in patients with adverse experiences during peak plasma levels after conventional tablets.

The effects of methyldopa and alprenolol were compared in I5 patients with previously untreated essential hypertension. The patients were randonly allocated to start treatment with one of the drugs. All

Based on sampling from official census lists a sample of middle-aged women was obtained in five different age strata; 38, 46, 50, 54 and 60 years. Based on date of birth a sub-set was sampled for maximal exercise testing. The participation rate was 81% and 194 women underwent the test. In sixteen women the test was interrupted due to poor cooperation or clinical contra-indications against continued loading. 54% of the women considered the maximal load to be at least very straining according to a standardized scale for perceived exertion. The average maximal load decreased from 113 to 98 W with advancing age. In the highest age group only 16% exceeded 130 W compared to 43% in the youngest group. Maximum heart rate decreased with age but maximum respiratory frequency and perceived exertion did not. Systolic blood pressure 2 min after maximal work increased with age. Minnesota Code items 4:1-3 and 5:1-3 were demonstrated in 30% of the women, mainly in the older age strata. Other ECG-abnormalities were uncommon. Despite the widely differing incidence of myocardial infarction these ischaemic ECG-abnormalities were as common in women as in a comparative sample of men. This observation questions the traditional interpretation of the exercise induced ECG response in women.