EFFECT OF TIMOLOL ON CARDIOPULMONARY EXERCISE PERFORMANCE IN MEN AFTER MYOCARDIAL-INFARCTION

The effect of the nonselective beta-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 (VO2), oxygen (O2) 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 VO2 decreased from 25.3 +/- 4.7 to 21.4 +/- 3.5 ml/min/kg (-15%, p < 0.001). O2 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), VO2 decreased from 18.5 +/- 4.3 ml/min/kg by 10% (p < 0.001), O2 pulse increased from 11.5 +/- 2.0 ml/beat by 30% (p < 0.001). The results indicate that timolol significantly reduced peak VO2, heart rate and exercise time at peak exercise. The increased O2 pulse at maximal level of exercise only partially compensated for the reduction in heart rate. At submaximal exercise, VO2 and heart rate were reduced during timolol treatment, and the increase in O2 pulse more completely compensated for the reduced heart rate. The results indicate that the use of beta-blockade for secondary prophylaxis substantially compromises functional capacity at peak and submaximal exercise.