Effects of propranolol and timolol on left ventricular volumes during exercise in patients with coronary artery disease

The hemodynamic effects of beta-receptor blocking agents on the ejection fraction of patients with coronary artery disease during exercise have been studied previously using radionuclide techniques. Left ventricular volume measurements and the peak systolic pressure/end-systolic volume (PSP/ESV) index have been shown to be variables of left ventricular function that are less influenced by preload and afterload than is ejection fraction. Left ventricular volumes and PSP/ESV were therefore measured in 18 patients with proven coronary artery disease in the control state and after 2 weeks of daily maintenance therapy with either 240 mg propranolol or 60 mg timolol. Values at rest and during symptom-limited upright exercise were compared using the first pass technique and a multicrystal scintillation camera. Left ventricular volumes were measured by the area-length method. Because there was no difference between the propranolol and timolol groups, the results for both groups were combined. The ejection fraction at rest after beta-receptor blocker treatment was not significantly different from pretreat-ment measurements because of an increase in both enddiastolic and end-systolic volumes (p < 0.01). However, the value for peak systolic pressure/end-systolic volume (PSP/ESV) index at rest was lower after treatment. The exercise ejection fraction was greater after treatment (p < 0.01), owing to an increase in end-diastolic volume and unchanged end-systolic volume. In addition, there was a significant improvement in the directional change in the PSP/ESV ratio between rest and exercise from pretreatment to treatment (-1.1 ± 2.5 to +0.2 ± 1.2, p < 0.02). Despite this evidence for improved left ventricular function with beta-receptor blocker therapy, the left ventricular functional response to exercise as measured by the change in PSP/ESV ratio did not normalize with therapy. Comparisons of regional functional changes during exercise before and after treatment showed improvement or no change in ischemic segments and no change in nonischemic segments. These data suggest that beta-receptor blockers improve global left ventricular function slightly by reversing the ischemic response, but at the same time, blunt the inotropic response of the normal exercising heart muscle to sympathetic stimulation.