The role of diastolic ventricular interaction in abnormal cardiac baroreflex function in chronic heart failure

Baroreflex abnormalities have been well documented in both patients with chronic heart failure and experimental animal models of heart failure. These abnormalities are associated with increased mortality and probably contribute to neurohumoral activation. While it is likely that several mechanisms contribute to reduced baroreflex sensitivity, it has been difficult to explain why baroreflex control mechanisms during acute volume unloading in patients with severe chronic heart failure should be directionally opposite to those in normal subjects. Volume unloading normally causes a reduction in baroreceptor activity, and hence an increase in sympathetic outflow; however, patients with chronic heart failure develop attenuated increases or paradoxical reductions in forearm vascular resistance, muscle sympathetic nerve activity, and noradrenaline spillover. It has been suggested that this probably represents paradoxical activation of left ventricular (LV) mechanoreceptors, but why LV receptors should behave in such a fashion has not been determined. In the setting of diastolic ventricular interaction, the filling of the left ventricle is constrained by the surrounding pericardium and right ventricle. In these patients, the reduction in right ventricular (RV) volume that normally occurs during acute volume unloading allows for an increase in LV end-diastolic volume (as opposed to the reduction in LV volume that normally occurs). We have demonstrated this to be important in some patients with chronic heart failure, and observed that baroreflex control of forearm vascular resistance was markedly impaired in these patients. We propose that the increase in LV volume that occurred during volume unloading would increase LV mechanoreceptor activity, and could therefore explain the paradoxical reductions in sympathetic outflow. As discussed, this has important therapeutic implications.