Effect of timolol on cardiopulmonary exercise performance in men after myocardial infarction

Abstract

The effect of the nonselective β blocker timolol on maximal cardiopulmonary exercise performance was evaluated in 28 men with previous myocardial infarction without effort angina (mean age 63 ± 8 years). Patients were randomized to placebo or timolol (10 mg twice daily) for 4 weeks and then crossed over to the alternative therapy in a double-blind manner. At the completion of each treatment period, patients underwent symptom-limited maximal cardiopulmonary exercise on a cycle ergometer. Exercise time, heart rate, oxygen consumption (VO 2), oxygen (O 2) pulse and respiratory exchange ratio were measured at peak exercise and at a submaximal exercise level defined at a respiratory exchange ratio of 1.00. Timolol treatment reduced peak heart rate from 153 ± 11 to 102 ± 14 beats/min (−33%, p <0.001). Exercise time decreased from 680 ± 91 to 633 ± 78 seconds (−7%, p <0.001). Peak VO 2 decreased from 25.3 ± 4.7 to 21.4 ± 3.5 ml/min/kg (−15%, p <0.001). O 2 pulse increased from 12.9 ± 1.9 to 16.7 ± 2.3 ml/beat (+29%, p <0.001). Peak respiratory exchange ratio did not change significantly, indicating comparable effort. At submaximal exercise, defined at a respiratory exchange ratio of 1.00, there was no difference in exercise time between placebo and timolol. Heart rate decreased with timolol compared with placebo, from 126 ± 16 beats/min by 31% (p <0.001), VO 2 decreased from 18.5 ± 4.3 ml/min/kg by 10% (p <0.001), O 2 pulse increased from 11.5 ± 2.0 ml/beat by 30% (p <0.001). The results indicate that timolol significantly reduced peak VO 2, heart rate and exercise time at peak exercise. The increased O 2 pulse at maximal level of exercise only partially compensated for the reduction in heart rate. At submaximal exercise, VO 2 and heart rate were reduced during timolol treatment, and the increase in O 2 pulse more completely compensated for the reduced heart rate. The remits indicate that the use of β blockade for secondary prophylaxis substantially compromises functional capacity at peak and maximal exercise.