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 ch ronic heart failure and experimental animal models of heart failure. These abnormalities are associated with increased mortality and probably contribu te to neurohumoral activation. While it is likely that several mechanisms c ontribute to reduced baroreflex sensitivity, it has been difficult to expla in why baroreflex control mechanisms during acute volume unloading in patie nts with severe chronic heart failure should be directionally opposite to t hose in normal subjects. Volume unloading normally causes a reduction in ba roreceptor activity, and hence an increase in sympathetic outflow; however, patients with chronic heart failure develop attenuated increases or parado xical reductions in forearm vascular resistance, muscle sympathetic nerve a ctivity, and noradrenaline spillover. It has been suggested that this proba bly represents paradoxical activation of left ventricular (LV) mechanorecep tors, but why LV receptors should behave in such a fashion has not been det ermined. In the setting of diastolic ventricular interaction, the filling of the lef t ventricle is constrained by the surrounding pericardium and right ventric le. 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 normall y occurs). We have demonstrated this to be important in some patients with chronic heart failure, and observed that baroreflex control of forearm vasc ular resistance was markedly impaired in these patients. We propose that th e increase in LV volume that occurred during volume unloading would increas e LV mechanoreceptor activity, and could therefore explain the paradoxical reductions in sympathetic outflow. As discussed, this has important therape utic implications.