Peripheral vasodilatation determines cardiac output in exercising humans: insight from atrial pacing

Abstract

Key points• During exercise, cardiac output is regulated to match oxygen delivery to the metabolic demand.• This study evaluated the role of heart rate and peripheral vasodilation in the regulation of cardiac output during exercise.• We increased heart rate by atrial pacing in 10 healthy male individuals during three different conditions: at rest, during exercise and during femoral arterial ATP infusion at rest.• Increasing the heart rate by atrial pacing by up to 54 beats min −1 did not increase cardiac output in any of the three given conditions as there was a proportional decrease in stroke volume.• These results indicate that cardiac output is regulated by changes in peripheral vasodilatation, whereas an increase in heart rate is less important.Abstract In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral vasodilatation in the regulation of cardiac output during steady-state exercise, we measured central and peripheral haemodynamics in 10 healthy male subjects, with and without atrial pacing (100-150 beats min −1 ) during: (i) resting conditions, (ii) one-legged knee extensor exercise (24 W) and (iii) femoral arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P < 0.05), whereas cerebral perfusion remained unchanged. During atrial pacing increasing heart rate by up to 54 beats min −1 , cardiac output did not change in any of the three conditions, because of a parallel decrease in stroke volume (P < 0.01). Atrial pacing increased mean arterial pressure (MAP) at rest and during ATP infusion (P < 0.05), whereas MAP remained unchanged during exercise. Atrial pacing lowered central venous pressure (P < 0.05) and pulmonary capillary wedge pressure (P < 0.05) in all conditions, whereas it did not affect pulmonary mean arterial pressure. Atrial pacing lowered the left ventricular contractility index (dP/dt) (P < 0.05) in all conditions and plasma noradrenaline levels at rest (P < 0.05), but not during exercise and ATP infusion. These results demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output. Abbreviations BVC, brain vascular conductance; CVP, central venous pressure; dP/dt max , left ventricular contractility index; HR, heart rate; LBF, leg blood flow; LVC, leg vascular conductance; MAP, mean arterial pressure; MCA, middle cerebral artery; MCA V mean , brain vascular conductance index; PAMP, pulmonary artery mean pressure; PCWP, pulmonary capillary wedge pressure;Q , cardiac output; SV, stroke volume; SVC, systemic vascular conductance; V mean , mean blood velocity;V O 2 , oxygen uptake.

Skeletal Muscle Signaling and the Heart Rate and Blood Pressure Response to Exercise

“…Instead, the lower SV during atrial pacing was related to a reduction in ventricular filling pressure, suggesting that an unaltered venous return was the mechanism by which CO was maintained during the pacing trial. The similar CO and blood pressure levels with and without atrial pacing is in agreement with observations in resting and exercising humans 28 and dogs. 29 Collectively, these observations suggest that CO and O 2 delivery are regulated mainly by peripheral O 2 demand 28,30 and that the regulation can occur independently of the lower sympathetic activation and consequently HR, blood pressure, and ventilatory response to exercise in the trained state.…”

“…The similar CO and blood pressure levels with and without atrial pacing is in agreement with observations in resting and exercising humans 28 and dogs. 29 Collectively, these observations suggest that CO and O 2 delivery are regulated mainly by peripheral O 2 demand 28,30 and that the regulation can occur independently of the lower sympathetic activation and consequently HR, blood pressure, and ventilatory response to exercise in the trained state. The lower HR during exercise in the trained state is paralleled by a higher SV that occurs secondary to the reduced cardiac afterload.…”

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

“…Thus flow was controlled at fixed levels in contrast to the usual hindlimb preparation that permits blood flow to rise in response to contractions. FIGURE 21 shows that at rest, carotid occlusion, a maneuver that stimulates sympathetic outflow to the muscle, caused an increase in pressure in the perfusion circuit consistent with the interpretation that there was vasoconstriction in the hindlimb (375).…”

“…Cerebral blood flow is ϳ0.75 l/min or 15% of resting cardiac output. This absolute value does not change dramatically during exercise or perhaps increases slightly (21,180). Coronary blood flow increases three-to fourfold from 0.15-0.20 to 0.5-0.8 l/min during maximum exercise driven primarily by the increased heart rate (137,236,254,296,351,482).…”

Cardiovascular Adaptations to Exercise Training

“…The increase in stroke volume during exercise at a given absolute workload in the trained state is a result of an increase in blood volume, an augmented left ventricular end-diastolic volume, and cardiac preload (198,236) as well as a lower cardiac afterload (arterial pressure) (132,296). Notably, evidence suggests that cardiac output during exercise is regulated by peripheral oxygen demand (16,156) and that this regulation is independent of training status (296).…”