Heart rate and QT interval in subjects adapted to beta-blockade: bradycardia and hypotension as uncorrelated adaptations.

Subjects in whom it was found that after a month's treatment with beta-blockers there was a fall of not less than 10 mmHg in systolic blood pressure persisting 54 h after cessation of treatment were considered to have "adapted". Significant falls of blood pressure and heart rate were observed, and were still present after two further weeks of treatment with placebo, but these adaptations were not correlated with each other. Fourteen hypertensive patients and five normotensive subjects received oral propranolol 80 mg, or metoprolol 100 mg, twice daily for 5 days. They were studied before treatment, and 54 h after the last dose. Drug administration was continued for a further 26 days, and the subjects were again examined 54 h after cessation of treatment. Blood was withdrawn at the times of study and contained negligible amounts of drug in the plasma. Records were made of blood pressure and ECG at rest and after exercise, the post-exercise QT being measured at a heart rate of exactly 100 beats per minute, obviating the need for any correction of QT. QT intervals were significantly prolonged, both at rest and on exercise. Responses to intravenous propranolol 10 mg or metoprolol 20 mg were also measured during the study periods, and no hypersensitivity to the drugs was found at rest or after exercise.