Mast Cell Stabilization added to Beta‐Adrenergic Receptor Blockade has beneficial effects on Left Ventricular Function, Remodeling and Isolated Cardiomyocyte function in Canine Mitral Regurgitation

Left ventricular (LV) dilatation in volume overload of isolated mitral regurgitation (MR) is marked by increased adrenergic drive and loss of extracellular matrix (ECM). Because mast cells are increased throughout the course of MR and may promote ECM degradation, we hypothesized that β 1 ‐receptor blockade (β 1 ‐RB) + mast cell stabilization (MCS) attenuates LV remodeling after 4 months of canine MR. β 1 ‐RB +/− MCS did not attenuate the 30% reduction in ECM induced by MR. Three‐dimensional (3‐D) magnetic resonance imaging showed a 75% increase in LV end‐diastolic volume and a 45% increase in LV 3‐D radius/wall thickness (R/T) in MR +/− β 1 ‐RB vs. normals. MCS did not attenuate LV dilatation but improved LV end‐systolic (ES) volume and 3‐D LVES R/T, resulting in improved LV fractional shortening. β 1 ‐RB + MCS prevented cardiomyocyte elongation caused by MR + β 1 ‐RB alone and normalized Ca ++ transients, which were decreased in MR alone. In addition, isoproterenol induced Ca ++ transients were improved with MCS. LV peak + dP/dt max was significantly decreased in MR + β 1 ‐RB and normalized by MCS. β 1 ‐ RB + MCS reversed cardiomyocyte elongation and improved LV chamber function compared to β 1 ‐RB alone without improving ECM loss, suggesting that MCS has a direct effect on cardiomyocyte remodeling and function in isolated MR. Supported by NIH RO1 HL54816 and SCCOR P50HL077100.