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 myocardial beta-adrenergic receptor (beta-AR) system. In this study, the effects of G protein-coupled receptor kinase 5 (GRK5) overexpression on myocardial performance were directly assessed in the hearts of transgenic mice using an isolated work-performing murine heart preparation and computerized analysis 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-dependent cardiac output, contractility, stroke work, stroke volume, and heart rate were compared between the two groups. RESULTS: Significant decreases in preload-dependent cardiac output and contractility were observed in the mice with GRK5 overexpression when compared with control group mice and occurred in association with significant decreases in stroke work and stroke volume. There was no significant difference in the average heart rate between the two groups. CONCLUSIONS: These data suggest that GRK5 upregulation may be partially responsible for alterations in myocardial function in chronic heart failure.
Chen, EP; Bittner, HB; Akhter, SA; Koch, WJ; Davis, RD
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