Initial Changes in β-Adrenergic Receptor Function during Development of Rapid Ventricular Pacing-Induced Heart Failure

Abstract

Current knowledge of the pathogenesis of myocardial failure is derived mainly from studies of chronic or end-stage failing hearts. However, the mechanisms responsible for early changes in contractile function prior to the onset of severe congestive heart failure and the accompanying complications such as fibrosis might be more important, especially for creating therapeutic strategies to reverse the process of heart failure. The canine model of rapid pacing-induced heart failure is ideal for these studies because there is a progressive impairment in cardiac function, with initial cardiac dysfunction prior to development of a large dilated heart and severe congestive heart failure [1–6]. Since this occurs in the absence of significant hypertrophy or fibrosis, it makes the interpretation of data less complicated. This model of pacing-induced failure is also characterized by decreased responsiveness to β-adrenergic receptor stimulation, as seen with chronic human heart failure [7–8]. Furthermore, this action can be observed early in the cardiac dysfunction stage. Therefore, the goal of this chapter is to review data from our laboratory concerning the early changes in the β-adrenergic-receptor-G-protein-adenylyl-cyclase signal transduction system induced by rapid ventricular pacing prior to the onset of heart failure [1–3].