Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis.
OBJECTIVE
Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-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 6-1/2 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.


CONCLUSIONS
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.
Hon
J K
JK
Department of Cardiothoracic Surgery, National Heart and Lung Institute at Royal Brompton Hospital, London, United Kingdom. j.hon@ic.ac.uk
Steendijk
P
P
Petrou
M
M
Wong
K
K
Yacoub
M H
MH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000254:growth & development; D006439:Hemodynamics / Q000187:drug effects; D011897:Random Allocation; D012756:Sheep; D013599:Systole; D013997:Time Factors; D017725:Ventricular Pressure / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D002976:Clenbuterol