Author:
Pat Betty,Killingsworth Cheryl,Denney Thomas,Zheng Junying,Powell Pamela,Tillson Michael,Dillon A. Ray,Dell'Italia Louis J.
Abstract
The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that β1-adrenergic receptor blockade (β1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. β1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by β1-RB. However, β1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171 ± 5 μm, P < 0.05) compared with normal (156 ± 3 μm) and MR (165 ± 4 μm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73 ± 0.31 vs. 5.02 ± 0.26%, P < 0.05) and normalized with β1-RB (4.73 ± 0.48%). In addition, stimulation with the β-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% ( P < 0.05) in β1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, β1-RB improved LV cardiomyocyte function and β-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
33 articles.
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