Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis

Objectives: Chronic pressure overload cardiac hypertrophy produces ventricu lar dysfunction. There is evidence that clenbuterol, a beta (2)-adrenocepto r agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure ove rload by means of pulmonary artery banding. Methods: Right ventricular pressure-volume loops were obtained in open-ches t sheep before and after 6 1/2 weeks of pulmonary artery banding by using m icromanometer conductance catheters. Animals were randomly assigned to trea tment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. Results: Acute pulmonary artery banding increased the right ventricular sys tolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 /- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean standard deviation]). Six weeks of treatment produced no significant differ ences in the body weight, heart weight, heart/body weight ratio, right vent ricular wall thickness, heart rate, and stroke volume between the groups. H owever, the slope of the end-systolic pressure-volume relation and the slop e of the first derivative of the fight ventricular developed pressure/end-d iastolic volume relation were significantly increased when compared with ba seline values in clenbuterol-treated animals but not in saline-treated anim als. Conclusion: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. T his has important implications for the use of pharmacologic agents in modul ating cardiac adaptation.