Comparison of spontaneous vs. metronome-guided breathing on assessment of vagal modulation using RR variability

R-R interval variability (RR variability) is increasingly being used as an index of autonomic activity. High-frequency (HF) power reflects vagal modulation of the sinus node. Since vagal modulation occurs at the respiratory frequency, some investigators have suggested that HF power cannot be interpreted unless the breathing rate is controlled. We hypothesized that HF power during spontaneous breathing would not differ significantly from HF power during metronome-guided breathing. We measured HF power during spontaneous breathing in 20 healthy subjects and 19 patients with heart disease. Each subject's spontaneous breathing rate was determined, and the calculation of HF power was repeated with a metronome set to his or her average spontaneous breathing rate. There was no significant difference between the logarithm of HF power measured during spontaneous and metronome-guided breathing [4.88 +/- 0.29 vs. 5.29 +/- 0.30 ln(ms(2)), P = 0.32] in the group as a whole and when patients and healthy subjects were examined separately. We did observe a small (9.9%) decrease in HF power with increasing metronome-guided breathing rates (from 9 to 20 breaths/min). These data indicate that HF power during spontaneous and metronome-guided breathing differs at most by very small amounts. This variability is several logarithmic units less than the wide discrepancies observed between healthy subjects and cardiac patients with a heterogeneous group of cardiovascular disorders. In addition, HF power is relatively constant across the range of typical breathing rates. These data indicate that there is no need to control breathing rate to interpret HF power when RR variability (and specifically HF power) is used to identify high-risk cardiac patients.     

Cardiac responses to first ever submergence in double-crested cormorant chicks (Phalacrocorax auritus)

Heart rates were recorded from double-crested cormorant chicks during their first ever and subsequent voluntary head submergences and dives, as well as during longer dives made after the chicks were accustomed to diving. Despite variation between chicks, the cardiac response to first ever and subsequent voluntary submergence (head submergences and dives) was similar to the response observed in adult cormorants. Upon submersion the heart rate fell rapidly when pre-submersion heart rate was high (325-350 beats min-1). The heart rate established within the first second of voluntary submergence was between 230 and 285 beats min-1, well above resting heart rate (143 beats min-1). The same initial cardiac response occurred during longer dives performed after the chicks were accustomed to diving. In these dives the heart rate remained at the level established on submersion, unlike the response observed in shallow diving adult cormorants in which the heart rate declined throughout the dive. The heart rate was also monitored in a separate group of chicks in which the first exposure to water was during whole body forced submergence. Again, the observed response was similar to the adult response, although the cardiac response of chicks to forced submergence was more extreme than to voluntary submergence. Our results do not support the hypothesis that learning (by conditioning or habituation) is involved in the cardiac adjustments to voluntary submergence. It is suggested that the initial cardiac adjustments are reflex in nature and this reflex is fully developed by the first submergence event. Although the nature of this reflex pathway is obscure, cessation of breathing before submersion and the close linkage between breathing and heart rate might provide a plausible mechanism.     

Study of cardiac, respiratory, and motor activities in rat fetuses

Development of the cardiac, respiratory, and motor activities in rat fetuses with preserved placental circulation was studied at the 16th, 18th, and 20th gestation days. The presence of three main movement types has been found: complexes of generalized activity, local movements, and jerks. In development of respiratory function, there is observed a gradual transition from individual inspirations to series of breathing movements and then to formation of periodic breathing episodes. At the studied period, the heart rate has been found to increase. The existence of the slow-wave modulations of the heart rate with a period of 2040 s has been revealed. Analysis of interrelations between the respiratory and motor systems has shown that in the 16-day fetuses, each breathing movement is accompanied by extensor jerk. By the 20th days of embryonic development (E20), uncoupling of the respiratory and motor activities occurs. Comparison of the activity observed in the cardiac and somatomotor systems has shown that at E16, the cardiac rhythm fluctuations do not depend on the motor excitation jerks. In the 18-day fetuses, brief slowing down (decelerations) of the cardiac rhythm appeared during the motor activity jerks, whereas at E20, on the contrary, an increase of frequency (accelerations) of the cardiac rhythm occurred.     

Cardiac responses to first ever submergence in double-crested cormorant chicks (Phalacrocorax auritus)

Heart rates were recorded from double-crested cormorant chicks during their first ever and subsequent voluntary head submergences and dives, as well as during longer dives made after the chicks were accustomed to diving. Despite variation between chicks, the cardiac response to first ever and subsequent voluntary submergence (head submergences and dives) was similar to the response observed in adult cormorants. Upon submersion the heart rate fell rapidly when pre-submersion heart rate was high (325–350 beats min⁻¹). The heart rate established within the first second of voluntary submergence was between 230 and 285 beats min⁻¹, well above resting heart rate (143 beats min⁻¹). The same initial cardiac response occurred during longer dives performed after the chicks were accustomed to diving. In these dives the heart rate remained at the level established on submersion, unlike the response observed in shallow diving adult cormorants in which the heart rate declined throughout the dive. The heart rate was also monitored in a separate group of chicks in which the first exposure to water was during whole body forced submergence. Again, the observed response was similar to the adult response, although the cardiac response of chicks to forced submergence was more extreme than to voluntary submergence. Our results do not support the hypothesis that learning (by conditioning or habituation) is involved in the cardiac adjustments to voluntary submergence. It is suggested that the initial cardiac adjustments are reflex in nature and this reflex is fully developed by the first submergence event. Although the nature of this reflex pathway is obscure, cessation of breathing before submersion and the close linkage between breathing and heart rate might provide a plausible mechanism.     

Cardio-respiratory adaptation to physical exercise and hypoxia after a high-altitude expedition.

Seven young, male subjects were tested before and immediately after 6 weeks high-mountain expedition. Cardio-respiratory measurements were performed at rest and during standard physical excercise (10 min, 100 W) when breathing atmospheric air or hypoxic mixture (14% O2 in N2). After the expedition an increased V o2 max (16% an average) and diminished heart rate response to submaximal exercise were found. This was observed during air and hypoxic mixture breathing. There was significant increase in stroke volume and cardiac output during the exercise. No significant differences in ventilatory parameters were found nor at rest or during exercise under condition of breathing atmospheric air or hypoxic mixture. No changes in erythrocyte count or haemoglobin concentration in the blood were found. The physiological changes which developed during high-mountain expedition were more dependent on physical that hypoxic training.     

Respiratory influences on non-linear dynamics of heart rate variability in humans

 The goal of our study was to determine whether evidence for chaos in heart rate variability (HRV) can be observed when the respiratory input to the autonomic controller of heart rate is forced by the deterministic pattern associated with periodic breathing. We simultaneously recorded, in supine healthy volunteers, RR intervals and breathing volumes for 20 to 30 min (1024 data point series) during three protocols: rest (control), fixed breathing (15 breath/min) and voluntary periodic breathing (3 breaths with 2 s inspiration and 2 s expiration followed by an 8 s breath hold). On both the RR interval and breathing volume series we applied the non-linear prediction method (Sugihara and May algorithm) to the original time series and to distribution-conserved isospectral surrogate data. Our results showed that, in contrast to the control test, during both fixed and voluntary periodic breathing the variability of breathing volumes was clearly deterministic non-chaotic. During all the three protocols, the RR-interval series’ non-linear predictability was consistent with one of a chaotic series. However, at rest, no clear difference was observed between the RR-interval series and their surrogates, which means that no clear chaos was observed. During fixed breathing a difference appeared, and this difference seemed clearer during voluntary periodic breathing. We concluded that HRV dynamics were chaotic when respiration was forced with a deterministic non-chaotic pattern and that normal spontaneous respiratory influences might mask the normally chaotic pattern in HRV. Received: 7 August 1995 / Accepted in revised form: 20 March 1997     

Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

Heart rate variability in subjects with different respiratory rates

The variability of the cardiac rhythm was studied in males with different initial respiratory rates. At rest and during voluntarily controlled breathing, subjects with medium respiratory rates were found to have a less variable heart rate than their counterparts with low or high respiratory rates.     

Interactions of respiration and the bradycardia of submersion in harbor seals.

Six harbor seals with percutaneous tracheostomies were artificially ventilated while immersed. Changes in the oxygen content of the inspired gas and in the minute-volume altered the magnitude of the bradycardia observed after the animal had been submerged for 30 s. The average heart rate in five seals changed from 16.7 (S.D. = 4.4) beats per minute during artificial ventilation with N2, to 58.7 (S.D. = 10.4) beats per minute while breathing air, but this cardiac chronotropic effect of oxygen was blocked by addition of 7% CO2 to the inspired gas. Ventilatory minute-volumes above approximately 3 litres/min caused cardiac acceleration in a manner related to ventilation; below this, changes in heart rate were inconsistent. While being artificially ventilated with air, the average heart rate in five seals changed from 16.5 beats per minute to 73.4 beats per minute as ventilation was increased from 0 to greater than 8 litres/min. These experiments demonstrate that O2, CO2, and ventilatory minute-volume have significant effects upon the heart rate of seals under water and suggest the presence of chemoreceptor-mediated effects on heart rate during submersion.     

Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control

Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants'' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology.     

Operation Everest II: preservation of cardiac function at extreme altitude

Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.     

Nocturnal periodic breathing at altitudes of 6,300 and 8,050 m

Nocturnal periodic breathing was studied in eight well-acclimatized subjects living at an altitude of 6,300 m [barometric pressure (PB) 350-352 Torr] for 3-5 wk and in four subjects during one night at 8,050 m altitude (PB 281-285 Torr). The measurements at 6,300 m included tidal volume by inductance plethysmography, arterial O2 saturation by ear oximetry (calibrated by arterial blood samples), electrocardiogram (ECG), and electrooculogram. At 8,050 m, periodic breathing was inferred from the cyclical variation in heart rate obtained from a night-long ECG record. All subjects at 6,300 m altitude showed well-marked periodic breathing with apneic periods. Cycle length averaged 20.5 s with 7.9 s apnea. Minimal arterial O2 saturation averaged 63.4% corresponding to a PO2 of approximately 33 Torr, i.e., approximately 6 Torr lower than the normal value at rest during daytime. This was probably the most severe hypoxemia of the 24-h period. At 8,050 m altitude, the cycle length averaged 15.4 s, much longer than predicted by a theoretical model. Cyclical variations in heart rate caused by periodic breathing occurred in all subjects, but abnormal cardiac rhythms such as ventricular premature contractions were uncommon. The severe arterial hypoxemia caused by periodic breathing may be an important determinant of tolerance to these great altitudes.     

Cardiac rhythm effects of .125-Hz paced breathing through a resistive load: Implications for paced breathing therapy and the polyvagal theory

This study examined the psychophysiological effects of slow-paced breathing while subjects breathed through external respiratory resistive loads. Twenty-four normal volunteers completed four 5-min trials of paced breathing (.125 Hz) through an inspiratory resistive wire mesh screen (0 to 25 cm H₂O/L/s). Each trial was followed by a 5-min rest trial. There was evidence for hyperventilation and/or fatigue during paced breathing. Also, respiratory sinus arrhythmia (RSA) was elevated in the first minute of paced breathing, and then declined toward baseline. Heart period decreased during paced breathing trials, and fell significantly below baseline during rest periods. These data suggest decreased vagus nerve activity and/or sympathetic activation, following an initial increase in parasympathetic activity during paced breathing. They are not consistent with the use of .125-Hz paced breathing as a relaxation technique, particularly during respiratory resistive stress. Finally, although RSA and average heart period changed synchronouslywithin paced breathing and rest conditions, they diverged incomparisons between pacing and rest. This dissociation suggests that different mechanisms mediate these two cardiac parameters. These data are consistent with Porges' theory that vagal influences on tonic heart rate are mediated by the combined effect of vagal projections from both the nucleus ambiguus and the dorsal motor nucleus, while RSA is mediated only through the nucleus ambiguus alone.     

Guidelines for paediatric life support. Paediatric Life Support Working Party of the European Resuscitation Council.

The paediatric life support working party of the European Resuscitation Council was set up in 1992 with the aim of producing guidelines for basic and advanced paediatric resuscitation that would be acceptable throughout Europe. The commonest cause of cardiac arrest in children is problems with the airway. The resulting difficulties in breathing and the associated hypoxia rapidly cause a severe bradycardia or asystole. In contrast, adults have primary cardiac events resulting in ventricular fibrillation. This important difference in the pathogenesis of paediatric and adult cardiac arrest is reflected in these European Resuscitation Council guidelines, which complement those already published for adults.     

Acute alterations in stroke volume during exercise at 3,100 m altitude.

Following 3 weeks exposure to an altitude of 3,100 m, the cardiac output response to upright submaximal exercise was examined in 3 healthy subjects breathing ambient air and breathing 60% oxygen. The procedure allowed acute alteration of the 2 conditions within a single testing period of 30 min, 60% oxygen breathing either preceding or following breathing ambient air. Cardiac output was also measured in two of the subjects during maximal exercise under these two conditions. Administration of the high oxygen inspirate during exercise had little effect on the level of cardiac output but resulted in an immediate bradycardia and a dramatic increase of approximately 16% in stroke volume. Stroke volumes during maximal exercise were also increased by approximately 10% by the administration of high oxygen. It is suggested that the condition of decreases exercise stroke volume which develops with chronic exposure to altitude may be largely the result of diminished myocardial contractility stemming from a condition of myocardial hypoxia.     

Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal CO2 and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in CO2 and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/min with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal CO2 and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 +/- 5.0% (P < 0.0001) and 24.4 +/- 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal CO2 and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders.     

Distribution of Daily Breathing Rates For Use in California's Air Toxics Hot Spots Program Risk Assessments

Data were combined from a study measuring breathing rates at various activities and two activity pattern studies to generate breathing rate distributions for children and adults. The children and adult breathing rate distributions were combined using a Monte Carlo technique to generate a breathing rate distribution for a lifetime spanning ages 0 to 70. The children's breathing rate distribution has a mean, standard deviation, median and 95^th percentile of 452, 67.7, 441, and 581 L/kg-day, respectively. The adult breathing rate distribution has a mean, standard deviation, median and 95^th percentile of 232, 64.6, 209, and 381 L/kg-day, respectively. The simulated 70-year distribution has a mean, standard deviation, median and 95^th percentile of 271, 57.9, 253, and 393 L/kg-day, respectively. The adult breathing rate distribution is based on 24-hour recall activity data that would not necessarily capture average activity patterns and therefore breathing rates. We utilized the human energy expenditure literature to validate the breathing rate distribution. We conclude that the breathing rate distribution is reasonable for chronic long-term risk assessment in California's Air Toxics Hot Spots program.     

Cardiac output and O2 consumption during inspiratory threshold loaded breathing

In this study, noninvasive measurements of cardiac output and O2 consumption were performed to estimate the blood flow to and efficiency of the respiratory muscles that are used in elevated inspiratory work loads. Five subjects were studied for 4.5 min at a respiratory rate of 18 breaths/min and a duty cycle of 0.5. Studies were performed at rest without added respiratory loads and at elevated inspiratory work loads with the use of an inspiratory valve that permitted flow only when a threshold pressure was maintained. Cardiac output and O2 consumption were calculated using a rebreathing technique. Respiratory muscle blood flow and O2 consumption were estimated as the difference between resting and loaded breathing. Work of breathing was calculated by integrating the product of mouth pressure and volume. Increases in cardiac output and O2 consumption in response of 4.5 min loaded breathing averaged 1.84 l/min and 108 ml/min, respectively. No increases were seen in response to 20-s loaded breathing. In a separate series of experiments on four subjects, though, cardiac output increased for the first 2 min then leveled off. These results indicate that the increase in cardiac output was a metabolic effect of the increased work load and was not caused primarily by the influence of the highly negative intrathoracic pressure on venous return. Efficiency of the respiratory muscles during inspiratory threshold loading averaged 5.9%, which was similar to measurements of efficiency of respiratory muscles using whole-body O2 consumption that have been reported previously in humans and in dogs.     

Voluntary and Involuntary Control of Breathing with Imposed Ventilation Parameters

To clarify the mechanisms of interaction between voluntary and involuntary control of respiratory movements in a waking human, respiratory patterns were studied during self-controlled artificial ventilation used in place of natural breathing. Seven subjects controlled both the duration of artificial inhalations and the flow rate of air at excess pressure, continuously adjusting their actions to obtain the sensation of comfortable breathing. At rest, pulmonary ventilation was higher during self-controlled artificial breathing than during natural breathing. This trend was also noted during exercise. A correlation was observed between the velocity of the movement that started air flow and the artificial ventilation volume (r = 0.91). During self-controlled artificial breathing, the subjects sometimes took natural breaths. Natural inhalations did not influence the beginning or end of an artificial inhalation. Information received from respiratory receptors was assumed to play a certain role in the self-control of artificial breathing.