Abstract 763: Increased Ventricular Function in vivo is Associated with Increased Myocyte Contractility in α-Dystrobrevin Knockout Mice
Spatial confinement of nitric oxide (NO) with its effecter proteins plays an important role in regulating ventricular function. Previous studies have documented an increase in myocyte contractility in nNOS-deficient mice. The α-dystrobrevin in the dystrophin-glycoprotein complex anchors the sarcolemma-associated nNOS. In this study, we examined the impact of the ablation of sarcolemmal nNOS alone on ventricular function by characterizing the α-dystrobrevin knockout mice (adbn−/−).
Methods: Tagged short-axis MR images of two months old adbn−/− mice (n=5) and age matched controls (n=7) were acquired. Maximum shortening was calculated from the 2D strain tensor using finite element analysis. Ventricular myocytes were isolated from adbn−/− mice (n=6) and age matched controls (n=6) using enzymatic digestion. The contraction of 15 electrically stimulated myocytes (0.5 Hz) was recorded for each heart. Myocyte contractility was quantified by maximum fractional shortening from changes in cell length during contraction.
Results: MRI studies demonstrated that in vivo myocardial contractility was significantly increased in adbn−/− mice. The magnitude of maximum shortening (principal strain) was increased throughout the whole left ventricle (Figure A⇓). Myocyte contractility also increased significantly from 8.5±1.4% in wild-type to 10.1±2.0% in adbn−/−mice (p<0.01, Figure B⇓).
Conclusion: MRI observed increase of in vivo myocardial contraction in adbn−/− mice is associated with an increase in myocytes contractility due to the absence of sarcolemmal nNOS, suggesting the sarcolemma-associated nNOS as a key player in regulating ventricular contractility.