Alteration of humoral and peripheral vascular responses during graded exercise in heart failure

We hypothesized that performance of exercise during heart failure (HF) woul d lead to hypoperfusion of active skeletal muscles, causing sympathoactivat ion at lower workloads and alteration of the normal hemodynamic and hormona l responses. We measured cardiac output, mean aortic and right atrial press ures, hindlimb and renal blood flow (RBF), arterial plasma norepinephrine ( NE), plasma renin activity (PRA), and plasma arginine vasopressin (AVP) in seven dogs during graded treadmill exercises and at rest. In control experi ments, sympathetic activation at the higher workloads resulted in increased cardiac performance that matched the increased muscle vascular conductance . There were also increases in NE, PRA, and AVP. Renal vascular conductance decreased during exercise, such that RBF remained at resting levels. After control experiments, HF was induced by rapid ventricular pacing, and the e xercise protocols were repeated. At rest in HF, cardiac performance was sig nificantly depressed and caused lower mean arterial pressure, despite incre ased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoco nstriction and by elevated NE, PRA, and AVP levels, but it did not increase at the mildest workload. Beyond mild exercise, sympathoactivation increase d, accompanied by progressive renal vasaconstriction, a fall in RBF, and ve ry large increases of NE, PRA, and AVP. As exercise intensity increased, pe ripheral vasoconstriction increased, causing arterial pressure to rise to n ear normal levels, despite depressed cardiac output. However, combined with redirection of RBF, this did not correct the perfusion deficit to the hind limbs. We conclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, with heavie r workloads, sympathoactivation begins at lower workloads and becomes progr essively exaggerated at higher workloads, thus altering distribution of blo od flow.