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J Thorac Cardiovasc Surg 2001;122:767-774
© 2001 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

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

From the Department of Cardiothoracic Surgery,^a National Heart and Lung Institute at Royal Brompton Hospital, London, United Kingdom, and the Department of Cardiology,^b Leiden University Medical Center, Leiden, The Netherlands.

This study was supported by the British Heart Foundation project grant PG/98079.

Received for publication July 26, 2000. Revisions requested Nov 15, 2000; revisions received Dec 11, 2000. Accepted for publication Jan 17, 2001. Address for reprints: Professor Sir Magdi Yacoub, Department of Cardiothoracic Surgery, Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom (E-mail: j.hon{at}ic.ac.uk).

Objectives: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a ß₂-adrenoceptor 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 overload by means of pulmonary artery banding.
Methods: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment 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 systolic 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 differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals.
Conclusion: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.

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