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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/H2321    most recent 00746.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pat, B. Articles by Dell'Italia, L. J. Search for Related Content PubMed PubMed Citation Articles by Pat, B. Articles by Dell'Italia, L. J.

Dissociation between cardiomyocyte function and remodeling with β-adrenergic receptor blockade in isolated canine mitral regurgitation

¹Center for Heart Failure Research, Department of Medicine, University of Alabama at Birmingham, and ²Birmingham Department of Veteran Affairs, Birmingham; and ³Department of Electrical Engineering and ⁴College of Veterinary Medicine, Auburn University, Auburn, Alabama

Submitted 17 July 2008 ; accepted in final form 6 October 2008

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.

heart failure; volume overload