EXPERIMENTAL STUDY
differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation
Shintaro Nemoto, MD, PhD*,
Masayoshi Hamawaki, MD*,
Gilberto De Freitas, BS, BA* and
Blase A. Carabello, MD, FACC* ,*
* Department of Medicine, Division of Cardiology, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina, USA
the Ralph H. Johnson Department of Veterans Affairs, Charleston, South Carolina, USA
Manuscript received December 12, 2001;
revised manuscript received March 19, 2002,
accepted April 5, 2002.
* Reprint requests and correspondence: Dr. Blase A. Carabello, Chief, Medical Service (111), Houston Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, Texas 77030, USA.
blaseanthony.carabello{at}med.va.gov
OBJECTIVES: The goal of this study was to determine the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor blockers in experimental chronic mitral regurgitation (MR), gaining knowledge using methods difficult to apply in humans.
BACKGROUND: Both ACE inhibitors and beta-blockers are cornerstones in the treatment of human congestive heart failure. However, the roles of these treatments for chronic MR is unclear.
METHODS: Mitral regurgitation was created in 11 closed-chest dogs. Three months after the creation, the ACE inhibitor lisinopril 20 mg was given orally daily. After three months of lisinopril therapy, the beta-blocker atenolol was added to lisinopril for another three months. Atenolol was begun at a dose of 12.5 mg daily and increased gradually to 100 mg daily. Hemodynamics and left ventricular (LV) function were assessed throughout the study.
RESULTS: Regurgitant fraction was consistently >50% over the course of this study. Pulmonary capillary wedge pressure and LV end-diastolic pressure were significantly increased after three months of MR and decreased during both lisinopril and the combined therapy in which it was not different from baseline. Left ventricular contractility measured by the end-systolic stiffness constant was depressed from 3.66 ± 0.20 to 2.65 ± 0.12 (p < 0.05) at three months of MR and rose insignificantly after lisinopril treatment (2.99 ± 0.17). When atenolol was added, it rose significantly and returned to normal (3.50 ± 0.22, p < 0.05).
CONCLUSIONS: Although lisinopril significantly reduced preload, its effect on LV contractility was insignificant in experimental MR. Conversely, atenolol, when added to lisinopril, achieved maximum hemodynamic benefit and also restored LV contractility.
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Abbreviations and Acronyms
| | ACE | | angiotensin-converting enzyme | | ANOVA | | analysis of variance | | BW | | body weight | | EDP | | end-diastolic pressure | | EDS | | end-diastolic stress | | ESS | | end-systolic stress | | MR | | mitral regurgitation | | LV | | left ventricle/ventricular | | PCWP | | pulmonary capillary wedge pressure | | RF | | regurgitant fraction |
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