Myocardial function in hearts with transgenic overexpression of the G protein-coupled receptor kinase 5

Background. Chronic heart failure is associated with impairment of the myoc ardial beta -adrenergic receptor (beta -AR) system. In this study, the effe cts of G protein-coupled receptor kinase 5 (GRK5) overexpression on myocard ial performance were directly assessed in the hearts of transgenic mice usi ng an isolated work-performing murine heart preparation and computerized an alysis of functional data. Methods. A controlled experimental study was performed to evaluate cardiac function in both transgenic mice with a 30-fold overexpression of GRK5 (n = 9, 23 to 29 g) and littermate controls (n = 10, 22 to 29 g). Preload-depen dent cardiac output, contractility, stroke work, stroke volume, and heart r ate were compared between the two groups. Results. Significant decreases in preload-dependent cardiac output and cont ractility were observed in the mice with GRK5 overexpression when compared with control group mice and occurred in association with significant decrea ses in stroke work and stroke volume. There was no significant difference i n the average heart rate between the two groups. Conclusions. These data suggest that GRK5 upregulation may be partially res ponsible for alterations in myocardial function in chronic heart failure. ( C) 2001 by The Society of Thoracic Surgeons.