Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans

Abstract

The aim of this study was to test our hypothesis that both phasic cardiac vagal activity and tonic pulmonary vagal activity, estimated as respiratory sinus arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to improve the efficiency of pulmonary gas exchange in humans. We examined the effect of blocking vagal nerve activity with atropine on pulmonary gas exchange. Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and respiratory frequency through a respiratory circuit with a respiratory analyser. Arterial partial pressure of O 2 (P aO 2 ) and arterial oxygen saturation (S pO 2 ) were measured, and alveolar-toarterial P O 2 difference (D A−aO 2 ) was calculated. Anatomical dead space (V D,an ), alveolar dead space (V D,alv ) and the ratio of physiological dead space to tidal volume (V D,phys /V T ) were measured. Electrocardiogram was recorded, and the amplitude of R-R interval variability in the high-frequency component (RRIHF) was utilized as an index of RSA magnitude. These parameters of pulmonary function were measured before and after administration of atropine (0.02 mg kg −1 ). Decreased RRIHF (P < 0.01) was accompanied by decreases in P aO 2 and S pO 2 (P < 0.05 and P < 0.01, respectively) and an increase in D A−aO 2 (P < 0.05). Anatomical dead space, V D,alv and V D,phys /V T increased (P < 0.01, P < 0.05 and P < 0.01, respectively) after atropine administration. The blockade of the vagal nerve with atropine resulted in an increase in V D,an and V D,alv and a deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our findings suggest that both phasic cardiac and tonic pulmonary vagal nerve activity contribute to improve the efficiency of pulmonary gas exchange in hypoxic conscious humans. The cardiovascular system mediates the interchange of oxygen and carbon dioxide between the lungs and the tissues (Richter et al. 1991;Coleridge et al. 1997). A high degree of co-ordination between the cardiovascular and respiratory system has been required from the earliest stages of vertebrate evolution (Taylor et al. 1999). The vagal nervous system is involved in the function of both systems and may play a role in co-ordinating their activity. Phasic activity of the cardiac vagal outflow is closely linked to respiration and produces respiratory sinus arrhythmia (RSA), which causes increases in heart rate during inspiration and decreases during expiration. It may improve pulmonary gas exchange by matching pulmonary capillary perfusion to alveolar ventilation during each respiratory cycle (Hayano et al. 1996;Hayano & Yasuma, 2003). Hayano et al. (1996) demonstrated that in vagotomized dogs whose heart rates were controlled with a pacemaker, artificially generated RSA improved the efficiency of gas exchange as a result of decreasing the ratio of physiological dead space to tidal volume (V D,phys /V T ) and the fraction of intrapulmonary shunt. Giardino et al. (2003) also reported that the magnitude of RSA was associated with efficiency of pulmonary gas exch...

Changes in dead space can explain part of the reduction in gas exchange efficiency found, not necessarily linked to respiratory sinus arrhythmia

“…However, our point is that is seems plausible to us that an increase of about 4% in V D,phys (39 ml out a V T of 980 ml) is capable of causing a decrease in P aO2 of about the same fraction, with a validated model of the underlying physiological phenomena supporting this idea. From this point of view, the evidence shown by Ito et al (2006) cannot be interpreted as a rejection of the hypothesis that changes in V D,phys are, at least in part, the mechanism linking changes in RSA and those in gas exchange efficiency.However, further simulations we performed in which we increased only V D,an from baseline to post-atropine values showed that 1 mmHg out of the 1.3 mmHg overall P aO2 decrease (more than 75%) can be related to the increase in V D,an alone. It is well established in the literature that an increase in V D,an following atropine administration (as reported by the authors) is a direct effect of the atropine-induced reduction in tonic activity of the pulmonary vagal nerves (Severinghaus & Stupfel, 1955).…”

“…J. Hayano and colleagues pioneered the research in this area and suggested that RSA-related changes in physiological dead space to tidal volume ratio (V D,phys /V T ) and the fraction of intrapulmonary shunt could be the links between RSA and efficiency of gas exchange, given that in a canine model both parameters increase when RSA is present under negative pressure ventilation produced by diaphragm pacing and under RSA changes induced by direct vagal stimulation (Hayano et al 1996). From this point of view, the paper of Ito et al (2006) is a necessary and valuable effort to investigate to what extent such a suggestion can be extended to humans during spontaneous ventilation and RSA. The results presented by the authors clearly indicate that vagal blockade using atropine results in attenuation of RSA, increase of V D,phys (mainly the anatomical dead space, V D,an ) and deterioration of pulmonary oxygenation.…”

Indirect measures of human vagal withdrawal during head-up tilt with and without a respiratory acidosis

“…However, there is certainly no guarantee of a reciprocal change in R-R interval and the HF component of HRV given that the frequency domain components of HRV provide a measure of the strength of oscillation, irrespective of whether the heart rate is high or low. For example, HF cardiac variability may be abolished with administration of atropine while mean heart rate remains unchanged [30]. Equally, HF cardiac variability will increase markedly with a respiratory acidosis with minimal [25] or no change [23] in R-R interval.…”

“…However, Cooke et al [14] reported a decrease in HRV at respiratory frequency with head-up tilt, consistent with the findings of the present study. It has been suggested that phasic cardiac vagal activity (defined by the magnitude of respiratory sinus arrhythmia) contributed to the efficiency (12) 788 (164) 79 (44) 776 (170) 61 (38) 79 (14) Reported values are mean (SD) for 14 subjects of pulmonary gas exchange in humans, whereby the matching of pulmonary perfusion to ventilation decreases intrapulmonary shunt and alveolar dead space [30,37,38]. When atropine abolished the HF component of HRV in healthy, seated humans at rest [30], small but significant decreases in Pa O 2 and arterial oxygen saturation were recorded.…”

“…It has been suggested that phasic cardiac vagal activity (defined by the magnitude of respiratory sinus arrhythmia) contributed to the efficiency (12) 788 (164) 79 (44) 776 (170) 61 (38) 79 (14) Reported values are mean (SD) for 14 subjects of pulmonary gas exchange in humans, whereby the matching of pulmonary perfusion to ventilation decreases intrapulmonary shunt and alveolar dead space [30,37,38]. When atropine abolished the HF component of HRV in healthy, seated humans at rest [30], small but significant decreases in Pa O 2 and arterial oxygen saturation were recorded. However, lowering PET CO 2 with HUT may improve gas exchange efficiency independent of changes in respiratory sinus arrhythmia if the ventilation-perfusion matching is improved in an upright healthy lung [39].…”