Heart Failure Switches RV Inotropic Responses from Negative to Positive

Abstract

Right ventricular (RV) failure is a common but poorly understood disease. It is assumed that an understanding of RV failure can be extrapolated from studies of the left ventricle (LV). Hypothesis: RV failure is similar physiologically to LV failure. Methods: Using intact RV and LV trabeculae from nonfailing and failing mouse hearts, we measured inotropic (force) responses to alpha-1 adrenergic receptor (α1-AR) stimulation, and assessed myofilament function using skinned trabeculae. Results: Figure shows typical force records from electrically paced trabeculae after α1-AR stimulation (arrows). For nonfailing RV trabeculae, force decreased 27±3%, mean±SEM, n=9. In marked contrast, for failing RV trabeculae, force increased 49±6%, n=21. This switch in inotropic response was paralleled by a switch in the myofilament response to α1-ARs from decreased Ca2+ sensitivity (nonfailing) to increased Ca2+ sensitivity (failing). For LV trabeculae, inotropic and myofilament responses to α1-ARs were not different in nonfailing versus failing hearts. Conclusions: In failing RV, the inotropic response to α1-ARs is switched from negative to positive due to a switch in the myofilament response to α1-ARs from decreased to increased Ca2+ sensitivity. Reject study hypothesis, because RV failure is different physiologically from LV failure.View Large Image | View Hi-Res Image | Download PowerPoint Slide