THERAPY AND PREVENTION PHARMACOLOGY Long-term effects of xamoterol

The purpose of the study was to examine whether the prolonged administration of the 3,-adrenoceptor partial agonist xamoterol could improve left ventricular diastolic function and affect the global remodeling process of the left ventricle after anterior myocardial infarction. In 22 patients with anterior myocardial infarction and single-vessel disease, left ventricular angiography (+ Millar) was performed under basal conditions 1 to 2 months after the acute myocardial infarction. Eight patients were then treated for 3 months with placebo and 14 were treated with xamoterol (200 mg bid) and a second left ventricular angiographic study was performed. Angiograms were digitized frame by frame to derive the diastolic pressure-volume relationship and to compute wall stress. An index of elastic myocardial stiffness was computed at a constant stress of 30 kdynes/cm2 before and after treatment. To evaluate changes in left ventricular shape, segmental areas in anterior and inferior segments were computed and compared at end-diastole and end-systole. After xamoterol, left ventricular end-diastolic pressure and mean diastolic wall stress decreased (from 24 5 to 15 + 5 mm Hg and from 57 + 32 to 38 + 22 kdynes/cm2, respectively; both p < .01 vs baseline and vs placebo). These changes were accompanied by a downward shift in the diastolic pressure-volume relationship and by a decrease in the index ofmyocardial stiffness from 526 + 270 to 371 + 194 kdynes/cm2 (p < .02). Left ventricular shape was not significantly altered by xamoterol but a significant remodeling of the left ventricular silhouette was evident at end-systole, as indicated by an improvement in the ratio (anterior segmental area/inferior segmental area) from 1.14 to 1.02 (median values; p < .025 vs baseline and vs placebo). It is concluded that impaired diastolic function after myocardial infarction is not entirely caused by fibrotic scar tissue but also by some active alterations in the function of viable myocardial areas that can be improved by therapy with xamoterol. Further studies are needed to determine whether the improvement in diastolic function and the systolic left ventricular remodeling are directly related. Circulation 77, No. 5, 1081-1089, 1988. RECENT STUDIES have shown that global remodeling of the left ventricle occurs immediately after infarction, involving structural changes in both infarcted and noninfarcted segments.1-6 The result of this process is a dilated left ventricle, with some degree of regional hypertrophy in noninfarcted segments and some degree of infarct expansion in the infarcted segment.3 In some instances, ventricular dilatation after myocardial infarction may continue for months,7 From the Cardiac Catheterization and Interventional Cardiology Unit, Division of Cardiology, University of Louvain, Brussels. Supported in part by grants SPPS 83-88/51 from the Belgian Government. Address for correspondence: H. Pouleur, M.D., University of Louvain, School of Medicine, Avenue Hippocrate, 55 Box 5560, B-1200 Brussels, Belgium. Received March 31, 1987; revision accepted Dec. 30, 1987. Vol. 77, No. 5, May 1988 inducing further left ventricular dysfunction and heart failure. According to the model proposed by McKay et al.,3 the trigger for these progressive changes in left ventricular geometry is increased diastolic wall stress. Thus, any intervention that lowers diastolic wall stress might be beneficial during the remodeling process. The intravenous administration of xamoterol (ICI 118,587, Corwin), a new 3,-adrenoceptor partial agonist,8 has been shown to reduce mean diastolic wall stress in patients with a previous myocardial infarction,9 while producing only minimal changes in systolic function or myocardial oxygen uptake. Other studies confirmed that short-term dosing with xamoterol consistently reduced left ventricular filling pressure, not only at rest but also during exercise.'0 Preliminary results indi1081 by gest on A ril 0, 2017 http://ciajournals.org/ D ow nladed from