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

Abstract

We hypothesized that performance of exercise during heart failure (HF) would lead to hypoperfusion of active skeletal muscles, causing sympathoactivation at lower workloads and alteration of the normal hemodynamic and hormonal responses. We measured cardiac output, mean aortic and right atrial pressures, 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 experiments, 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 exercise protocols were repeated. At rest in HF, cardiac performance was significantly depressed and caused lower mean arterial pressure, despite increased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoconstriction and by elevated NE, PRA, and AVP levels, but it did not increase at the mildest workload. Beyond mild exercise, sympathoactivation increased, accompanied by progressive renal vasoconstriction, a fall in RBF, and very large increases of NE, PRA, and AVP. As exercise intensity increased, peripheral vasoconstriction increased, causing arterial pressure to rise to near normal levels, despite depressed cardiac output. However, combined with redirection of RBF, this did not correct the perfusion deficit to the hindlimbs. We conclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, with heavier workloads, sympathoactivation begins at lower workloads and becomes progressively exaggerated at higher workloads, thus altering distribution of blood flow.

Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise

“…So, in summary, alteration of all three mechanisms may contribute to the lack of increase in LV contractile state with MMR activation in HF. Our results are in accordance with previous investigations where it was shown that the muscle metaboreflex is still capable of generating a pressor response during mild to moderate exercise in HF dogs, although the mechanisms of this response are different compared with those observed in normal conditions (11,12). In HF conditions, the pressor response must depend on responses within the peripheral vasculature (vasoconstriction), because the increase in CO is virtually abolished.…”

“…No exercise was performed in that study. Previous studies from our laboratory (11,12) have shown that in pacing-induced HF dogs, when MMR was activated during mild to moderate dynamic exercise, the increase in CO was significantly attenuated and the pressor response was more dependent on responses within the peripheral vasculature that result from increases in sympathetic outflow as well as the secretion of vasoactive hormones. In the present study after the induction of HF, we observed that SV and end-systolic pressure decreased.…”

“…Our group has previously demonstrated in this model that after induction of HF, during moderate exercise any mechanical terminal aortic occlusion elicits important increases in SNA, as evidenced by increases in arterial levels of plasma norepinephrine, marked peripheral vasoconstriction, and exaggerated release of vasopressin and renin (11,12,34). The inability of one animal to perform moderate exercise long enough to observe MMR responses in HF limited the number of observations in this setting to only four animals; however, none of these four animals showed any noticeable change in E max or PRSW in this setting (similar to all 5 during mild exercise); therefore, we are confident that the statistical conclusions reached are valid within the confines of this experimental approach.…”

“…After completion of the control experiments, congestive heart failure was induced via rapid ventricular pacing. This technique has been widely accepted to create chronic model of LV failure and has been utilized by others and us previously (11,12,19,37). Briefly, the right ventricular pacing electrodes were connected to a pacemaker set at 240 beats/min for ϳ30 days, and the experiments were repeated.…”

Spontaneous baroreflex control of heart rate versus cardiac output: altered coupling in heart failure

“…Briefly, the right ventricular pacing electrodes were connected to an external pacemaker set at 240 -250 beats/min for ϳ30 days. After an induction of modest HF (defined as resting tachycardia, reduced CO, SV, and maximum and minimum first derivative of left ventricular pressure) as described in our previous studies (8,9,14,28), the experiments were repeated. The pacemaker was turned off before each experiment, and data collection began after the hemodynamic variables had reached steady state (ϳ30 min).…”