The repeated sit-to-stand maneuver is a superior method for cardiac baroreflex assessment: a comparison with the modified Oxford method and Valsalva maneuver.

Baroreflex assessment has diagnostic and prognostic utility in the clinical and research environments, and there is a need for a reliable, simple, noninvasive method of assessment. The repeated sit-to-stand method induces oscillatory changes in blood pressure (BP) at a desired frequency and is suitable for assessing dynamic baroreflex sensitivity (BRS). However, little is known about the reliability of this method and its ability to discern fundamental properties of the baroreflex. In this study we sought to: 1) evaluate the reliability of the sit-to-stand method for assessing BRS and compare its performance against two established methods (Oxford method and Valsalva maneuver), and 2) examine whether the frequency of the sit-to-stand method influences hysteresis. Sixteen healthy participants underwent three trials of each method. For the sit-to-stand method, which was performed at 0.1 and 0.05 Hz, BRS was quantified as an integrated response (BRSINT) and in response to falling and rising BP (BRSDOWN and BRSUP, respectively). Test retest reliability was assessed using the intraclass correlation coefficient (ICC). Irrespective of frequency, the ICC for BRSINT during the sit-to-stand method was ≥0.88. The ICC for a rising BP evoked by phenylephrine (PEGAIN) in the Oxford method was 0.78 and ≤0.5 for the remaining measures. During the sit-to-stand method, hysteresis was apparent in all participants at 0.1 Hz but was absent at 0.05 Hz. These findings indicate the sit-to-stand method is a statistically reliable BRS assessment tool and suitable for the examination of baroreflex hysteresis. Using this approach we showed that baroreflex hysteresis is a frequency-dependent phenomenon.

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.

Cardioventilatory coupling and inter-breath variability in children referred for polysomnography.

Measures of respiratory variability including cardioventilatory coupling (CVC), were examined in 8 Down syndrome (DS), 4 Prader Willi syndrome (PWS) and 42 non-syndromic children (median age 7 years) referred for diagnostic polysomnography. Inspiratory onsets (I) and corresponding ECG R waves were determined, I-I, R-R and R-I intervals derived, and ventilatory frequency (f), standard deviation of f (SDf), coefficient of variation of f (CVf), median I-I and kurtosis and skewness I-I calculated. Proportional Shannon Entropy of the RI(-1) interval (SHα) was measured to quantitate CVC. SHα varied with age (p=0.02), oxygen saturation (p<0.05) and PWS diagnosis (p=0.001) in Stage 4 but not REM sleep. SDf and CVf varied with sleep state (p<0.00001) as did kurtosis I-I (p<0.0001) and skewness I-I (p=0.004). Ventilatory frequency decreased with age in REM sleep (p=0.03) and increased in obese children in REM (p=0.02) and Stage 4 sleep (p=0.004). Sleep state influences respiratory variability in children and CVC may confer a physiological advantage in children with PWS.

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.

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.

Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious humans during spontaneous respiration.

Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. However, recent studies showed that, under stress, RSA dissociates from vagal tone, indicating that separate mechanisms might regulate phasic and tonic vagal activity. This dissociation has been linked to the hypothesis that RSA improves pulmonary gas exchange through preferential distribution of heartbeats in inspiration. We examined the effects of hypercapnia and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat distribution throughout the respiratory cycle in 12 volunteers. We found that hypercapnia, but not hypoxemia, was associated with significant increases in heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase remained statistically significant after adjustment for respiratory rate, tidal volume, and HR. Moreover, the RSA amplitude increase was associated with a paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean amplitude ratio derived from spectral analysis, which is consistent with RSA-vagal dissociation. Although hypercapnia was associated with a significant increase in the percentage of heartbeats during inspiration, this association was largely secondary to increases in the inspiratory period-to-respiratory period ratio, rather than RSA amplitude. Additional model analyses of RSA were consistent with the experimental data. Heartbeat distribution did not change during hypoxemia. These results support the concept of RSA-vagal dissociation during hypercapnia; however, the putative role of RSA in optimizing pulmonary perfusion matching requires further experimental validation.

Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy, and sinoaortic denervation in the anesthetized rat.

Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and inspiratory activity, is a major determinant of breath-to-breath variation in observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this to adjustments of respiratory timing by baroreceptor afferent impulses to the central respiratory pattern generator. A mathematical model of this hypothesis indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time is dependent on the heart rate (HR), the rate of the intrinsic respiratory oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent impulse. Failure to account for HR and f(i) may explain the inconsistent results from previous attempts to identify the neural pathways involved in CVC. Cognizant of these interactions, we factored in the HR-to-f(i) ratio in our examination of the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing 29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the assumption of a relatively constant f(i), CVC could be examined across a range of HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o) ratio, and breath-to-breath respiratory period variability and demonstrated the loss of these relations after baroreceptor elimination. Sham experiments (n = 8) showed that these changes were not due to surgical stress. Our data support the notion that inspiratory timing can be influenced by cardiac afferent activity. We conclude that the putative cardiovascular input arises from the arterial baroreceptors and that the vagus nerve is not critical for CVC.

Knowledge of and attitudes towards resuscitation in New Zealand high-school students.

BACKGROUND: Introducing cardiopulmonary resuscitation (CPR) training in the high-school curriculum has been widely recommended as a long-term strategy to educate the wider community. Although CPR has been included in the New Zealand school curriculum, it is listed as an optional subject only. AIM: To assess the attitude towards and knowledge of CPR in 16-17-year-old high-school students in New Zealand. METHODS: Questionnaires were administered to 494 students aged 16-17 years across six high schools in Wellington, New Zealand. Both knowledge and attitude were evaluated in the questionnaire. RESULTS: Students showed poor theoretical knowledge, with a mean (SD) score of 5.61 (2.61) out of a maximum score of 18. Although there was no difference between male and female students, those who had received previous first-aid training (70%) showed greater knowledge (6.04 (2.56)) than their untrained counterparts (4.91 (2.24); p = 0.001). Those students with a positive attitude towards CPR and first-aid training (63%) acquired a higher knowledge score (6.12 (2.4)) than those with a negative attitude (17%; 4.65 (2.5); p = 0.001). Students with negative associations were also less likely to want to learn more about CPR and first aid (11%) when compared with those with positive associations (92%), and indicated less willingness to perform CPR on a stranger (negative v positive, 47% v 70%). CONCLUSIONS: These findings suggest that although most high-school students are willing and motivated to learn CPR, a smaller percentage of students had a negative attitude towards CPR that would act as a barrier to future learning or performance of resuscitation. Introducing CPR training to high schools is still recommended; however, this study shows the need to associate this training with positive references in an attempt to assist those for whom negative attitude may present as a barrier to learning and retaining CPR knowledge.

The sound of silence is music to the heart.

The underlying tempo of different types of music may have an effect on heart rate and blood pressure.

Quantal breathing frequency variation in halothane anaesthetised neonatal rats.

We examined the changes in cardioventilatory synchronisation and breathing frequency variability that occur during early postnatal development in anaesthetised rats. Five-minute periods of heart rate and inspiratory timing data were recorded from 26 halothane anaesthetised, spontaneously breathing rats aged 2-14 days. The presence of cardioventilatory synchronisation was determined by examining the timing relationship between inspiratory onset and the preceding ECG R waves. We observed synchronisation at all ages, and the degree of synchronisation present (measured as the Shannon entropy of the interval between inspiration and the immediately preceding R wave) did not correlate with age. Frequent apnoeas were observed in the respiratory frequency time series. The duration of these apnoeas was close to either one or two times the duration of the immediately preceding breath. We suggest that these "dropped breaths" may be the consequence of a resetting of the respiratory oscillator just prior to initiation of the breath, or a gating process beneath the oscillator that intermittently blocks the mechanical initiation of breaths. Dropped breaths were seen commonly in rats up to 11 days of age, but rarely in 11-14-day old rats, and were not associated with the presence or absence of cardioventilatory synchronisation.

Effect of automatic external defibrillator audio prompts on cardiopulmonary resuscitation performance.

OBJECTIVES: To determine the effectiveness of the cardiopulmonary resuscitation (CPR) audio prompts in an automatic external defibrillator in 24 lay subjects, before and after CPR training. METHODS: Untrained subjects were asked to perform CPR on a manikin with and without the assistance of audio prompts. All subjects were then trained in CPR, and retested them eight weeks later. RESULTS: Untrained subjects who performed CPR first without audio prompts performed poorly, with only (mean (SD)) 24.5% (32%) of compressions at the correct site and depth, a mean compression rate of 52 (31) per minute, and with 15% (32%) of ventilatory attempts adequate. Repeat performance by this group with audio prompts resulted in significant improvements in compression rate (91(12), p = 0.0002, paired t test), and percentage of correct ventilations (47% (40%), p = 0.01 paired t test), but not in the percentage correct compressions (23% (29%)). Those who performed CPR first with audio prompts performed significantly better in compression rate (87 (19), p = 003, unpaired t test), and the percentage of correct ventilations (51 (34), p = 0.003 unpaired t test), but not in the percentage of correct compressions (18 (27)) than those without audio prompts. After training, CPR performance was significantly better than before training, but there was no difference in performance with or without audio prompts, although 73% of subjects commented that they felt more comfortable performing CPR with audio prompts. CONCLUSIONS: For untrained subjects, the quality of CPR may be improved by using this device, while for trained subjects the willingness to perform CPR may be increased.

Fractal characteristics of breath to breath timing in sleeping infants.

We examined interbreath interval (IBI) time series of 19 term infants during active and quiet sleep for fractal properties using Fano factor analysis. For each time series we calculated the fractal exponent (alpha), comparing alpha for the original time series with two forms of surrogate data, a temporally independent surrogate set and an autoregressive surrogate set. alpha values were normally distributed between 0.79 and -0.22, and did not differ with sleep state. The fractal characteristics of the original time series were not retained in the temporally independent surrogate time series indicating that the distribution of intervals alone was not fractal, but were retained using autoregressive surrogates with an order of 10, suggesting that the fractal properties of the IBI time series were related to correlations between successive breaths. These observations suggest that some of the respiratory variability that occurs during sleep in infants, which in the past has been regarded as stochastic noise, may be the product of deterministic processes.

Inspiratory coupling to cardiac activity and to somatic afferent nerve stimulation in the anaesthetised rat.

We examined the ability of somatic afferent nerve stimulation to entrain inspiratory onset in the anaesthetized spontaneously breathing rat, and compared features of this stimulus-ventilatory coupling to entrainment of inspiratory onset by cardiac activity. In 14 rats prior to stimulation, we commonly observed a constant temporal alignment between ECG R waves and inspiratory onset (cardioventilatory coupling). Stimulation of a hamstring nerve at rates close to the heart rate also caused coupling (a constant stimulus to inspiratory onset interval), although this was highly dependent upon frequency of stimulation, with small changes in frequency causing a loss of coupling. In experiments where stimuli were given at constant intervals after ECG R waves, we observed no augmentation of coupling. Our results indicate that both cardiac and somatic afferent nerve activity is able to entrain inspiratory onset. We have suggested that coupling causes respiratory frequency to increase, and it is possible that this is a general mechanism whereby non-respiratory afferents act as stimulants or pacemakers to respiratory rhythm. The role of non-respiratory activity in initiating inspiration needs to be more fully recognised and studied.

Cardioventilatory coupling in resting human subjects.

In 48 conscious resting subjects we examined the temporal coupling of heart beat timing and the onset of inspiration (cardioventilatory coupling), and the relationship between coupling and spectral indices of autonomic function. Using the proportional Shannon entropy (SH(alpha)) of the RI(-1) interval (interval between inspiration and the preceding ECG R wave) as a measure of coupling we detected statistically significant coupling in 32 of the 48 subjects. This was confirmed by visual inspection of time series plots of RI intervals, in which coupling was evident as horizontal banding. Coupling resulted in a significant preference for whole number heart rate/respiratory frequency ratios. The strongest coupling was associated with low ventilatory frequency and high heart rate variability in the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency ranges, but was not related to blood pressure variability, or to a spectral measure of baroreflex sensitivity (alpha-index, low frequency range). There was no difference in coupling strength between males and females. We have previously described cardioventilatory coupling in spontaneously breathing anaesthetised subjects. The current study extends those observations by demonstrating that the qualitative features of coupling seen during anaesthesia are also observed in the conscious state. We conclude that the role of coupling in normal physiological respiratory control needs to be more widely explored.

Quantal ventilatory variability during spontaneous breathing anaesthesia.

BACKGROUND: Cardioventilatory coupling is the triggering of inspiratory onset by preceding cardiac activity. We have observed two forms of coupling with a bimodal ('quantal') variation of respiratory period. METHODS: We investigated the variables of inspiratory duration (TI), expiratory duration (TE), and tidal volume (VT) where respiratory period variation was bimodal. In 25 anaesthetized spontaneously breathing subjects we took 11 samples of recording where the variation of respiratory period was quantal. RESULTS: In eight of these epochs the variation in respiratory period was associated with fluctuations in the number of heart beats per breath (entrainment ratio) with a constant time interval between inspiration and the immediately preceding heart beat (coupling interval), which we define as pattern II coupling. During pattern II coupling, the quantal variations in respiratory period were entirely caused by variation in TE, with no associated changes in either TI or VT. The other three epochs with quantal variations in respiratory period were observed in pattern III coupling, where an alternating fluctuation in both entrainment ratio and coupling interval occurs. During pattern III coupling, quantal fluctuations were observed in TE, TI, and VT. IMPLICATIONS: Cross correlation analysis suggested that when pattern III was present, TI was dependent upon the preceding TE, which differs markedly from traditional views on the interaction between inspiratory and expiratory duration. VT was linearly related to TI, and so could also be determined by the preceding TE during this type of coupling.

Comparison of ease of use of three automated external defibrillators by untrained lay people.

The use of automated external defibrillators (AED) by lay people has the potential to markedly increase survival from community cardiac arrest. Wider public use of AEDs requires units that can be operated safely and effectively by people with minimal or no training. This study compares the use of three AEDs by untrained lay people regarding ease-of-use, safety, pad positioning and time to defibrillation. 24 subjects with no prior exposure to the use of AEDs were asked to perform simulated defibrillation on a manikin using three defibrillators: Zoll AEDPlus, Medtronic Physio-Control LifePak CR Plus and Philips/Laerdal HeartStart OnSite Defibrillator. Subjects' performance were videotaped and reviewed for time to defibrillate, pad positioning and safety. Subjects were asked to rate the three units in terms of ease-of-use. Average times to first shock were 74.8 s for the Physio-Control, 83.0 s for the Laerdal and 153.4 s for the Zoll defibrillator. Pad positioning was scored as correct in 23/24 Laerdal trials, 19/24 Physio-Control trials and 14/24 Zoll trials. 23 out of the 24 subjects rated the Zoll most difficult to use. All subjects safely stayed clear of the unit when required. The majority of subjects safely and effectively delivered defibrillating shocks without any prior training and within quite acceptable times. Untrained subjects find the Physio-Control and Laerdal Defibrillator easier to use than the Zoll device. Features of AED design that improved ease of use are discussed.

Comparison of heart rate variability in supine, and left and right lateral positions.

In order to determine whether differences exist in cardiac autonomic tone between different body positions that may be used in unconscious subjects, we examined beat-to-beat heart rate variability (HRV) in volunteers lying supine, and in left lateral and right lateral positions. We studied 24 subjects, aged 20-35 years in each of the three positions on one study day, and 6 subjects in each of the three positions on each of six different study days. In both groups of subjects we observed no difference in heart rate, respiratory frequency, total power (0.02-0.45 Hz) of HRV or the proportion of power in the high (0.15-0.45 Hz), low (0.08-0.15 Hz) or very low (0.02-0.08 Hz) frequency bands among the three positions. These results suggest that there are no cardiac autonomic tone advantages to be gained by placing a person in the recovery position on one side compared with the other.

Patterns of external chest compression.

We studied the performance of external chest compression by 20 fourth year medical students on 2 study days, separated by 5-7 weeks, 4-8 months after they had been initially trained in cardiopulmonary resuscitation (CPR). Our hypotheses were (1) that a given individual would perform external chest compressions in the same manner each time CPR was performed and (2) that the pattern of performance of chest compressions would be determined, in part, by the anthropometric characteristics of the rescuer. A Laerdal Skillmeter Resusci-Anne CPR manikin chest compression transducer was interfaced with an analogue-to-digital conversion board in a Macintosh LC III computer. Each subject on each study day performed four cycles of 15 compressions and two ventilations twice, once on a table (which raised the surface of the manikin sternum to 95 cm) and once on the floor. For each individual, on each attempt, we calculated the depth and rate of compressions, duty cycle, peak compression velocity, time to peak compression velocity and time to peak compression depth. In addition, we calculated the regression slope of compression depth versus compression number for each cycle of 15 chest compressions and over four cycles of compressions. Statistically significant correlations were observed between the first and second study days in each of the variables of chest compression measured, indicating that the performance of chest compressions was constant over time for a given individual. We observed that the depth of compression, duty cycle, time to peak compression, time to peak velocity and regression slope of depth of compressions versus compression number were significantly related to the height and weight of the rescuer.

Inspiratory timing during anaesthesia: a model of cardioventilatory coupling.

We describe a simple model of cardioventilatory coupling in which a hypothetical inspiratory pacemaker is stimulated by a signal related to cardiac action. At suitable values for the control variables (cardiac signal magnitude, heart rate, inspiratory pacemaker rate and inspiratory rate variability), the model was found to: (1) replicate all clinically described patterns of coupling; (2) predict variations in these described patterns and new patterns which were subsequently found in clinical time series; (3) simulate variations in clinically observed breathing frequency variations associated with each coupling pattern; (4) simulate the clinically observed distribution of coupling patterns between heart rate and breathing frequency; (5) explain the invariability of coupling below a critical heart rate/breathing frequency ratio; and (6) simulate the changes in breathing frequency and transitions between coupling patterns from the heart rate time series of human subjects. Although cardioventilatory coupling causes complex breathing rate irregularities during anaesthesia, these are readily explained by three variables, heart rate, intrinsic breathing frequency, and the strength of their interaction. This simple model, along with clinical observations of cardioventilatory coupling may provide a useful non-invasive method to study the respiratory central pattern generator.