Heart failure alters the strength and mechanisms of the muscle metaboreflex

Abstract

Heart failure alters the strength and mechanisms of the muscle metaboreflex. Am. J. Physiol. Heart Circ. Physiol. 278: H818-H828, 2000.-We hypothesized that excessive sympathoactivation observed during strenuous exercise in subjects with heart failure (HF) may result from tonic activation of the muscle metaboreflex (MMR) via hypoperfusion of active skeletal muscle. We studied MMR responses in dogs during treadmill exercise by graded reduction of terminal aortic blood flow (TAQ) before and after induction of HF by rapid ventricular pacing. At a low workload, in both control and HF experiments, large decreases in TAQ were required to elicit the MMR pressor response. During control experiments, this pressor response resulted from increased cardiac output (CO), whereas in HF CO did not increase; thus the pressor response was solely due to peripheral vasoconstriction. In HF, MMR activation also induced higher plasma levels of vasopressin, norepinephrine (NE), and renin. At a higher workload, in control experiments any reduction of TAQ elicited MMR pressor responses. In HF, before any vascular occlusion, TAQ was already below MMR control threshold levels and reductions in TAQ again did not result in higher CO; thus SAP increased via peripheral vasoconstriction. NE rose markedly, indicating intense sympathetic activation. We conclude that in HF, the MMR is likely tonically active at moderate workloads and contributes to the tonic sympathoactivation. dynamic exercise; hormones; dogs; Frank-Starling; rapid ventricular pacing WHEN OXYGEN DELIVERY to active skeletal muscle is insufficient for the ongoing metabolic demands, metabolites accumulate and stimulate afferents within the active skeletal muscle that elicit a powerful pressor response known as the muscle metaboreflex. Activation of the muscle metaboreflex during exercise elicits increases in heart rate, cardiac output, systemic arterial pressure, ventricular performance, central blood volume mobilization, and vasoconstriction in the renal and nonischemic active skeletal muscle vasculatures (9,11,12,14,16,17,22,23,25,33). In addition, metaboreflex activation can also increase the circulating levels of vasoactive hormones (13,18). These marked cardiovascular responses are buffered by arterial (23) and cardiopulmonary (4) baroreflexes. Studies from our laboratory and from others (11, 12, 16-18, 22, 23, 33) have shown that in dogs during mild exercise a clear threshold exists for metaboreflex activation, i.e., initial reductions in blood flow to active skeletal muscle (i.e., hindlimbs) do not elicit any metaboreflex responses. Only when oxygen delivery is reduced below a threshold level do substantial metaboreflex pressor responses occur (25). In contrast, during moderate workloads no clear threshold exists, indicating that the metaboreflex may be tonically active or that the prevailing level of blood flow approximates the threshold for the reflex, and any reduction in perfusion to the active skeletal muscle will engage the muscle metaboreflex (20,22,33).The cardiovas...

Prostaglandins do not contribute to the nitric oxide-mediated compensatory vasodilation in hypoperfused exercising muscle

“…This suggests that humans rely on local vasodilator mechanisms, and not a reflex increase in pressure, to restore blood flow to hypoperfused contracting muscle. In contrast, there is overwhelming evidence that suggests a pressor response is essential in the restoration of blood flow to underperfused hindlimbs of exercising dogs (12,22,23,30,35). The discrepant findings between our series of studies in humans and those performed in dogs may simply be related to species differences.…”

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

“…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.…”

“…In addition, in normal dogs, MMR activation causes substantial central blood volume mobilization (35), which maintains ventricular filling pressure that would otherwise decrease due to the rise in CO (43,45). In HF, this central blood volume mobilization still occurs, as evidenced by large increases in central venous pressure (11), but evidently even this increase in filling pressure is ineffective in raising CO during MMR activation. Prabhu and Freeman (38) reported that alteration of lengthdependent activation is a fundamental defect in the development and progression in HF.…”

“…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).…”