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 ₁-adrenergic receptor blockade (₁-RB) will attenuate LV remodeling after four months of MR in the dog. ₁-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using magnetic resonance imaging and three-dimensional (3-D) analysis, there was a 70% increase in LV end-diastolic (ED) volume/LV mass ratio, 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 ₁-RB. However, ₁-RB caused a significant increase in LVED length from base to apex compared to untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171 ± 5 µm, P < 0.05) compared to normal (156 ± 3 µm) and MR (165 ± 4 µm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared to normals (3.73 ± 0.31 vs. 5.02 ± 0.26%, P < 0.05) and normalized with ₁-RB (4.73 ± 0.48%). In addition, stimulation with the -adrenergic receptor agonist isoproterenol (25nM) increased cardiomyocyte fractional shortening by 215% (P < 0.05) in ₁-RB dogs compared to normal (56%) and MR (50%) dogs. In summary, ₁-RB improved LV cardiomyocyte function and -adrenergic receptor responsiveness in spite of 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.