Altered Arterial Baroreflex ‐ Muscle Metaboreflex Interaction in Heart Failure

Previous studies have shown that heart failure (HF) alters the strength and mechanisms of both the muscle metaboreflex and the arterial baroreflex during dynamic exercise. Muscle metaboreflex activation (MMA) in normal individuals increases mean arterial pressure (MAP) virtually solely by an increase in cardiac output (CO) whereas in HF, the mechanisms of this pressor response shift to peripheral vasoconstriction. In contrast, the pressor response evoked by baroreceptor unloading in normal subjects occurs primarily through peripheral vasoconstriction which is blunted in HF. How HF alters the interaction between these two powerful reflexes when activated simultaneously is unknown. We hypothesized that co‐activation of both reflexes in HF would cause a smaller increase in MAP and a larger vasoconstriction of the ischemic hindlimb vasculature, resulting in an attenuated restoration of blood flow to the ischemic muscle than that observed prior to HF. We activated the muscle metaboreflex in chronically instrumented canines during mild exercise (via graded reductions in hindlimb blood flow; HLBF) followed by baroreceptor unloading (via bilateral carotid occlusion; BCO) before and after induction of HF in the same animals. We observed that interaction between the two reflexes in normal animals is intimately dependent on the hemodynamic parameter investigated; MAP, conductance of all vascular beds except hindlimbs, and ventricular function all exhibited additive interaction, CO and renal conductance demonstrated occlusive interaction while HR exhibited facilitative interaction. Furthermore, BCO during MMA caused a preferentially larger vasoconstriction in non‐ischemic vascular beds, thereby redirecting blood flow to the ischemic vascular bed. However, after induction of HF, all cardiovascular responses except ventricular function exhibited occlusive interaction in response to baroreceptor unloading during MMA. The pressor response during co‐activation of reflexes occurred via substantial vasoconstriction of all vascular beds including the ischemic active muscle and there is no significant restoration of blood flow to the ischemic vascular bed. We conclude that larger vasoconstriction of ischemic active skeletal muscle during co‐activation of both reflexes in HF attenuates the restoration of blood flow to ischemic muscle. Support or Funding Information HL‐55473 and HL‐126706