Muscle chemoreflex-induced increases in right atrial pressure

Abstract

When oxygen delivery to active muscle is too low for the ongoing rate of metabolism, metabolites accumulate and stimulate sensory nerves within the muscle leading to sympathetic activation (muscle chemoreflex). To date, studies on this reflex have focused primarily on its ability to increase arterial pressure or on the activity of the nerves that mediate this response. Clearly, a rise in cardiac output (CO) constitutes an important adjustment, because it increases the total blood flow available to be distributed among organs competing for flow. However, increments in heart rate and contractility provide limited means of raising CO because of the inverse relationship that exists between CO and right atrial pressure (RAP) in the intact circulation. Our goal was to test whether muscle chemoreflex activation, achieved via graded reductions in hindlimb blood flow by partial vascular occlusion, elicits peripheral vascular adjustments that raise RAP. In four conscious dogs exercising on a treadmill at 3.2 km/h 0% grade, RAP was well maintained during reflex activation despite increases in CO and arterial pressure that are expected to reduce RAP. Thus peripheral vascular adjustments elicited by the reflex successfully defend RAP in a setting where it would otherwise fall. To isolate the effects of the reflex on RAP, CO was maintained constant by ventricular pacing in conjunction with β1-adrenergic blockade with atenolol. When the reflex was activated by reducing hindlimb blood flow from 0.6 to 0.3 l/min, RAP rose from 5.1 ± 0.8 to 7.4 ± 0.4 mmHg ( P < 0.05) despite continued large (40 mmHg) increases in arterial pressure. During heavier exercise (6.4 km/h 10% grade) in five dogs with normal ventricular function, the reflex raised RAP from 5.7 ± 0.9 to 6.6 ± 0.8 mmHg ( P < 0.05) despite increases in CO and arterial pressure. We conclude that the muscle chemoreflex is capable of eliciting substantial increases in RAP.

Muscle metaboreflex control of ventricular contractility during dynamic exercise

“…However, in a subsequent study (26) when HR was held constant, a similar increase in CO occurred due to MMR activation, but this time resulting from an increase in SV. In addition, this increase in SV, with HR maintained constant, was abolished by ␤-receptor blockade (30,35). Furthermore, White et al (43) showed that when HR is increased within a range similar to that observed with MMR activation but only via external pacing rather than increased SNA, little increase in CO occurred because of large decreases in SV.…”

“…As shown by Sheriff et al (35), this can be achieved via peripheral vascular adjustments that effectively defend cardiac filling pressure despite the increases in HR, CO, and MAP that would otherwise decrease it. In addition, the mean LV filling rate also must increase, because the tachycardia decreases the diastolic filling time (4,18).…”

“…Previous studies have shown that in normal dogs exercising at mild and moderate workloads, the increases in MAP elicited by this MMR activation are mainly due to increases in CO. The rise in CO likely results from increases in ventricular performance, HR, and central blood volume mobilization (26,35). In this way the MMR-induced increases in ventricular performance act to sustain or slightly increase stroke volume (SV) despite decreases in ventricular filling time due to the reflex tachycardia (2,26,44).…”

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

“…Komamura et al (20) demonstrated in dogs with pacing-induced HF that the failing ventricle is not able to increase SV in response to acute volume loads. 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.…”

“…In addition, MMR activation causes increases in cardiac output (CO), heart rate (HR), and plasma levels of vasoactive hormones and produces vasoconstriction in the renal and the nonischemic active skeletal muscle vasculature to partially restore arterial O 2 delivery and blood flow to the hypoperfused muscles (25,33,36). The rise in CO likely results from increases in ventricular performance, HR, and central blood volume mobilization (32,42,43). By this means the MMR-induced increases in ventricular performance act to slightly increase or sustain stroke volume (SV) despite decreases in ventricular filling time due to the reflex tachycardia (32,53).…”