P. Y. W. Sin

Respiratory sinus arrhythmia in conscious humans during spontaneous respiration.

Respiratory sinus arrhythmia (RSA) is the beat-to-beat fluctuation in heart rate at the frequency of the respiratory cycle. While it is common to study RSA under conditions of controlled breathing, where respiratory frequency, and sometimes tidal volume and inspiratory:expiratory ratio are controlled, the effect of controlled breathing on RSA is not clear. While not all studies exploring the effects of controlled breathing on RSA magnitude are consistent, some of the best-designed studies addressing this question did find a significant effect. In addition to respiratory timing influencing heartbeats, there is evidence that cardiac timing also influences respiratory timing, termed cardioventilatory coupling. Thus, the timing interactions between the cardiac and respiratory systems are complex, and bi-directional. Controlled breathing eliminates one aspect of this relationship, and studies designed to understand cardiorespiratory physiology conducted under these conditions need to be interpreted with an understanding that they may not represent normal physiology.

Respiratory modulation of cardiovagal baroreflex sensitivity

Emerging evidence has suggested that with minimal prerequisite training, slow deep breathing around 0.10 Hz can acutely enhance cardiovagal baroreflex sensitivity (BRS) in humans. Such reports have led to the speculation that behavioral interventions designed to reduce breathing frequency may serve a therapeutic role in ameliorating depressed baroreflex function in conditions such as chronic heart failure, essential hypertension, and obstructive airway disease. This study sought to test the hypothesis that slow controlled breathing acutely enhances cardiovagal baroreflex function in young healthy volunteers. Distinct from earlier studies, however, baroreflex function was examined (n = 30) using the classical pharmacological modified Oxford method, which enabled the assessment of cardiovagal BRS through experimentally driven baroreceptor stimulation across a wide range of blood pressures. For a comparison against existing evidence, spontaneous cardiovagal BRS was also assessed using the alpha-index and sequence method. Compared with fast breathing (0.25 Hz), slow breathing (0.10 Hz) was associated with an increase in the alpha-index (8.1 +/- 14 ms/mmHg, P < 0.01) and spontaneous up-sequence BRS (10 +/- 11 ms/mmHg, P < 0.01). In contrast, BRS derived from spontaneous down sequences and the modified Oxford method were unaltered by slow breathing. The lack of change in BRS derived from the modified Oxford method challenges the concept that slow breathing acutely augments arterial baroreflex function in otherwise healthy humans. Our results also provide further evidence that spontaneous BRS may not reflect the BRS determined by experimentally driven baroreceptor stimulation.

Influence of breathing frequency on the pattern of respiratory sinus arrhythmia and blood pressure: old questions revisited

Respiratory sinus arrhythmia (RSA) is classically described as a vagally mediated increase and decrease in heart rate concurrent with inspiration and expiration, respectively. However, although breathing frequency is known to alter this temporal relationship, the precise nature of this phase dependency and its relationship to blood pressure remains unclear. In 16 subjects we systematically examined the temporal relationships between respiration, RSA, and blood pressure by graphically portraying cardiac interval (R-R) and systolic blood pressure (SBP) variations as a function of the respiratory cycle (pattern analysis), during incremental stepwise paced breathing. The principal findings were 1) the time interval between R-R maximum and expiration onset remained the same ( approximately 2.5-3.0 s) irrespective of breathing frequency (P = 0.10), whereas R-R minimum progressively shifted from expiratory onset into midinspiration with slower breathing (P < 0.0001); 2) there is a clear qualitative distinction between pre- versus postinspiratory cardiac acceleration during slow (0.10 Hz) but not fast (0.20 Hz) breathing; 3) the time interval from inspiration onset to SBP minimum (P = 0.16) and from expiration onset to SBP maximum (P = 0.26) remained unchanged across breathing frequencies; 4) SBP maximum and R-R maximum maintained an unchanged temporal alignment of approximately 1.1 s irrespective of breathing frequency (P = 0.84), whereas the alignment between SBP minimum and R-R minimum was inconstant (P > 0.0001); and 5) beta(1)-adrenergic blockade did not influence the respiration-RSA relationships or distinct RSA patterns observed during slow breathing, suggesting that temporal dependencies associated with alterations in breathing frequency are unrelated to cardiac sympathetic modulation. Collectively, these results illustrate nonlinear respiration-RSA-blood pressure relationships that may yield new insights to the fundamental mechanism of RSA in humans.

Human sinus arrhythmia: inconsistencies of a teleological hypothesis

Respiratory sinus arrhythmia (RSA) may serve an inherent function in optimizing pulmonary gas exchange efficiency via clustering and scattering of heart beats during the inspiratory and expiratory phases of the respiratory cycle. This study sought to determine whether physiological levels of RSA, enhanced by slow paced breathing, caused more heart beats to cluster in inspiration. In 12 human subjects, we analyzed the histogram distribution of heart beats throughout the respiratory cycle during paced breathing at 12, 9, and 6 breaths/min (br/min). The inspiratory period-to-respiratory period ratio was fixed at approximately 0.5. RSA and its relationship with respiration was characterized in the phase domain by average cubic-spline interpolation of electrocardiographic R wave-to-R wave interval fluctuations throughout all respiratory cycles. Although 6 br/min breathing was associated with a significant increase in RSA amplitude (P < 0.01), we observed no significant increase in the proportion of heart beats in inspiration (P = 0.34). Contrary to assumptions in the literature, we observed no significant clustering of heart beats even with high levels of RSA enhanced by slow breathing. The results of this study do not support the hypothesis that RSA optimizes pulmonary gas exchange efficiency via clustering of heart beats in inspiration.

Interactions between heart rate variability and pulmonary gas exchange efficiency in humans

The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed‐rate cardiac pacemakers and 10 healthy control subjects, we recorded R–R intervals, respiratory flow, end‐tidal gas tension and the ventilatory equivalents for carbon dioxide   and oxygen   during ‘fast’ (0.25 Hz) and ‘slow’ paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, end‐tidal CO2,  and   were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5‐fold RSA amplitude increase in control subjects (39 ± 21 versus 97 ± 45 ms, P < 0.001), comparable   (main effect for breathing frequency, F(1,19) = 76.54, P < 0.001) and   reductions (main effect for breathing frequency, F(1,19) = 23.90, P < 0.001) were observed for both cohorts during slow breathing. In addition, the degree of   (r=−0.36, P= 0.32) and   reductions (r=−0.29, P= 0.43) from fast to slow breathing were not correlated to the degree of associated RSA amplitude enhancements in control subjects. These findings suggest that the association between RSA amplitude and pulmonary gas exchange efficiency during variable‐frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.

Relationship between cardioventilatory coupling and pulmonary gas exchange

Cardioventilatory coupling (CVC) is a temporal alignment between the heartbeat and inspiratory activity caused by pulsatile baroreceptor afferent activity. However, although first described over a century ago, the functional significance of CVC has yet to be established. One hypothesis is that baroreceptor triggering of inspiration positions heartbeats into phases of the respiratory cycle that may optimize pulmonary gas exchange efficiency. To test this hypothesis, we recruited ten patients with permanently implanted fixed‐rate cardiac pacemakers and instructed them to pace breathe at heart rate‐to‐respiratory rate (HR/f) ratios of 3·8, 4·0 and 4·2. This breathing protocol enabled us to simulate heartbeat distributions similar to those seen in the presence (4·0) and complete absence (3·8, 4·2) of CVC. Results showed that heart rate, mean arterial pressure, end‐tidal carbon dioxide and tidal volume remained unchanged across the three conditions (P>0·05). Pulmonary gas exchange efficiency, as determined by the ventilatory equivalents of carbon dioxide ( V·E/V·CO2 ) and oxygen ( V·E/V·O2 ) did not differ significantly by HR/f ratio (P = 0·29 and P = 0·70, respectively). These data suggest that CVC does not play a significant role in optimizing pulmonary gas exchange efficiency in humans.