Mathematical modeling of a chemoreceptor mechanism and the breakpoint of breath holding and experimental evaluation of the model

Using mathematical modeling of respiratory rhythm generation and the breakpoint of breath holding, the dependence of gas-exchange dynamics and the duration of voluntary breath holding on chemoreceptor regulation of the respiratory system was studied. With data from experiments on ten volunteers who had performed their maximum breath holding after maximum inspiration and after maximum expiration, it was shown that experimentally obtained values of the duration of breath holding after expiration were approximately 70% of those predicted by the model. This is an estimation of the contribution of chemoreceptor control to breath holding. The results support the concept of the key role of chemoreceptors at the breakpoint of breath holding.     

Assessment of influence of breath holding and hyperventilation on human postural stability with spectral analysis of stabilographic signal

The influence of breath holding and voluntary hyperventilation on the traditional stabilometric parameters and the frequency characteristics of stabilographic signal was studied. We measured the stabilometric parameters on a force platform (“Ritm”, Russia) in the 107 healthy volunteers during quiet breath, voluntary hyperventilation (20 seconds) and maximal inspiratory breath holding (20 seconds). Respiratory frequency, respiratory amplitude and ventilation were estimated with the strain gauge. We found that antero-posterior and medio-lateral sway amplitude and velocity as well as sway surface during breath holding and during quiet breathing were the same, so breath holding didn’t influence the postural stability. However, the spectral parameters in the antero-posterior direction shifted to the high frequency range due to an alteration of the respiratory muscles’ contractions during breath holding versus quiet breath. Voluntary hyperventilation caused a significant increase of all stabilographic indices that implied an impairment of the postural stability. We also found that the spectral indices shifted toward the high-frequency range, and this shift was much greater compared to that during breath holding. Besides, amplitudes of the spectral peaks also increased. Perhaps, such change of the spectral indices was due to distortion of the proprioceptive information because of increased excitability of the nerve fibers during hyperventilation. Maximal inspiratory breath holding caused an activation of the postural control mechanisms. It was manifested as an elevation of the sway oscillations’ frequency with no postural stability changes. Hyperventilation led to the greatest strain of the postural control and to a decrease of the postural stability, which was manifested as an increase of center of pressure oscillations’ amplitude and frequency.     

Spectral analysis of R-R interval variability in inspiratory breath holding in man at rest and during emotional strain

30 young males performed inspiratory breath holdings during expectation of an aversive stimulus and at relative rest. The consecutive R-R intervals of the ECG from breath-hold trial were analysed via spectral analysis of time series. Following parameters were ascertained for each breath holding: mean R-R interval, total R-R interval variability, breath-hold time and relative variability in three spectral bands 3-8 s, 8-12 s and 12-18 s. Neither of these variables was influenced by expectation of an aversive stimulus. The data were subsequently analysed by means of multivariate analysis. Three distinct frequency components were selected according to both histogram data and multivariate analysis. Their modal periods were 5-6 s, 12 s and 16 s respectively. The 8-12 s component of R-R interval variability dominated during breath holdings. The 3-8 s band bore a negative relationship to breath-hold time.     

Deposition of micrometer particles in pulmonary airways during inhalation and breath holding

We investigated how breath holding increases the deposition of micrometer particles in pulmonary airways, compared with the deposition during inhalation period. A subject-specific airway model with up to thirteenth generation airways was constructed from multi-slice CT images. Airflow and particle transport were simulated by using GPU computing. Results indicate that breath holding effectively increases the deposition of 5μm particles for third to sixth generation (G3-G6) airways. After 10s of breath holding, the particle deposition fraction increased more than 5 times for 5μm particles. Due to a small terminal velocity, 1μm particles only showed a 50% increase in the most efficient case. On the other hand, 10μm particles showed almost complete deposition due to high inertia and high terminal velocity, leading to an increase of 2 times for G3-G6 airways. An effective breath holding time for 5μm particle deposition in G3-G6 airways was estimated to be 4-6s, for which the deposition amount reached 75% of the final deposition amount after 10s of breath holding.     

Analysis of diaphragm movement during tidal breathing and during its activation while breath holding using MRI synchronized with spirometry

Using magnetic resonance imaging (MRI) in conjunction with synchronized spirometry we analyzed and compared diaphragm movement during tidal breathing and voluntary movement of the diaphragm while breath holding. Breathing cycles of 16 healthy subjects were examined using a dynamic sequence (77 slices in sagittal plane during 20 s, 1NSA, 240x256, TR4.48, TE2.24, FA90, TSE1, FOV 328). The amplitude of movement of the apex and dorsal costophrenic angle of the diaphragm were measured for two test conditions: tidal breathing and voluntary breath holding. The maximal inferior and superior positions of the diaphragm were subtracted from the corresponding positions during voluntary movements while breath holding. The average amplitude of inferio-superior movement of the diaphragm apex during tidal breathing was 27.3+/-10.2 mm (mean +/- SD), and during voluntary movement while breath holding was 32.5+/-16.2 mm. Movement of the costophrenic angle was 39+/-17.6 mm during tidal breathing and 45.5+/-21.2 mm during voluntary movement while breath holding. The inferior position of the diaphragm was lower in 11 of 16 subjects (68.75 %) and identical in 2 of 16 (12.5 %) subjects during voluntary movement compared to the breath holding. Pearson's correlation coefficient was used to demonstrate that movement of the costophrenic angle and apex of the diaphragm had a linear relationship in both examined situations (r=0.876). A correlation was found between the amplitude of diaphragm movement during tidal breathing and lung volume (r=0.876). The amplitude of movement of the diaphragm with or without breathing showed no correlation to each other (r=0.074). The movement during tidal breathing shows a correlation with the changes in lung volumes. Dynamic MRI demonstrated that individuals are capable of moving their diaphragm voluntarily, but the amplitude of movement differs from person to person. In this study, the movements of the diaphragm apex and the costophrenic angle were synchronous during voluntary movement of the diaphragm while breath holding. Although the sample is small, this study confirms that the function of the diaphragm is not only respiratory but also postural and can be voluntarily controlled.     

CO2-dependent components of sinus arrhythmia from the start of breath holding in humans

A substantial portion of sinus arrhythmia in conscious humans appears to be caused by the CO2-dependent central respiratory rhythm. Under some circumstances, therefore, sinus arrhythmia might indicate the presence of the central respiratory rhythm. Humans can voluntarily modify their central respiratory rhythm (e.g., by pacing breathing or by delaying or advancing breaths), but it is not clear what happens to it from the start of breath holding. In this study, we show that sinus arrhythmia persists from the start of breath holds prolonged by preoxygenation. We also show that some of the frequency components of sinus arrhythmia start within each subject's eupneic frequency range and change when end-tidal Pco2 is lowered or raised, as we would expect if the central respiratory rhythm continues from the start of breath holding. We discuss whether sinus arrhythmia can indicate if the central respiratory rhythm continues from the start of breath holding.     

Effect of lung volume on breath holding

The mechanism by which large lung volume lessens the discomfort of breath holding and prolongs breath-hold time was studied by analyzing the pressure waves made by diaphragm contractions during breath holds at various lung volumes. Subjects rebreathed a mixture of 8% CO2-92% O2 and commenced breath holding after reaching an alveolar plateau. At all volumes, regular rhythmic contractions of inspiratory muscles, followed by means of gastric and pleural pressures, increased in amplitude and frequency until the breakpoint. Expiratory muscle activity was more prominent in some subjects than others, and increased through each breath hold. Increasing lung volume caused a delay in onset and a decrease in frequency of contractions with no consistent change in duty cycle and a decline in magnitude of esophageal pressure swings that could be accounted for by force-length and geometric properties. The effect of lung volume on the timing of contractions most resembled that of a chest wall reflex and is consistent with the hypothesis that the contractions are a major source of dyspnea in breath holding.     

Cardiac performance in humans during breath holding

The effects on cardiac performance of high and low intrathoracic pressures induced by breath holding at large and small lung volumes have been investigated. Cardiac index and systolic time intervals were recorded from six resting subjects with impedance cardiography in both the nonimmersed and immersed condition. A thermoneutral environment (air 28 degrees C, water 35 degrees C) was used to eliminate the cold-induced circulatory component of the diving response. Cardiac performance was enhanced during immersion compared with nonimmersion, whereas it was depressed by breath holding at large lung volume. The depressed performance was apparent from the decrease in cardiac index (24.1% in the immersed and 20.9% in the nonimmersed condition) and from changes in systolic time intervals, e.g., shortening of left ventricular ejection time coupled with lengthening of preejection period. In the absence of the cold water component of the diving response, breath holding at the large lung volume used by breath-hold divers tends to reduce cardiac performance presumably by impeding venous return.     

Dosimetric impact of baseline drift in volumetric modulated arc therapy with breath holding

BackgroundWe investigated the change of dose distributions in volumetric modulated arc therapy (VMAT) under baseline drift (BD) during breath holding.Materials and methodsTen VMAT plans recalculated to a static field at a gantry angle of 0° were prepared for measurement with a 2D array device and five original VMAT plans were prepared for measurement with gafchromic films. These measurement approaches were driven by a waveform reproducing breath holding with BD. We considered breath holding times of 15 and 10 s, and BD at four speeds; specifically, BD0 (0 mm/s), BD0.2 (0.2 mm/s), BD0.3 (0.3 mm/s), and BD0.4 (0.4 mm/s). The BD was periodically reproduced from the isocenter along the craniocaudal direction and the shift during breath holding (Shift_BH) ranged 0–6 mm.The dose distribution of BD0.2, BD0.3 and BD0.4 were compared to that of BD0 using gamma analysis with the criterion of 2%/2 mm.ResultsThe mean pass rates of each Shift_BH were 99.8% and 98.9% at 0 mm, 96.8% and 99.4% at 2 mm, 94.9% and 98.6% at 3 mm, 91.5% and 98.4% at 4 mm, 70.8% and 94.1% at 4.5 mm, and 55.0% and 83.6% at 6 mm for the array and film measurements, respectively.ConclusionWe found significant differences in Shift_BH above 4 mm (ρ < 0.05). Hence, it is recommended that breath holding time should be shortened for patients to preserve the reproducibility of dose distributions.     

Effect of Breath Holding on Spleen Volume Measured by Magnetic Resonance Imaging

Objective

Ultrasonographic studies have demonstrated transient reduction in spleen volume in relation to apnea diving. We measured spleen volume under various respiratory conditions by MR imaging to accurately determine the influence of ordinary breath holding on spleen volumetry.

Materials and Methods

Twelve healthy adult volunteers were examined. Contiguous MR images of the spleen were acquired during free breathing and during respiratory manipulations, including breath holding at the end of normal expiration, breath holding at deep inspiration, and the valsalva maneuver, and spleen volume was measured from each image set based on the sum-of-areas method. Acquisition during free breathing was performed with respiratory triggering. The duration of each respiratory manipulation was 30 s, and five sets of MR images were acquired serially during each manipulation.

Results

Baseline spleen volume before respiratory manipulation was 173.0 ± 79.7 mL, and the coefficient of variance for two baseline measures was 1.4% ± 1.6%, suggesting excellent repeatability. Spleen volume decreased significantly just after the commencement of respiratory manipulation, remained constant during the manipulation, and returned to the control value 2 min after the cessation of the manipulation, irrespective of manipulation type. The percentages of volume reduction were 10.2% ± 2.9%, 10.2% ± 3.5%, and 13.3% ± 5.7% during expiration breath holding, deep-inspiration breath holding, and the valsalva maneuver, respectively, and these values did not differ significantly.

Conclusions

Spleen volume is reduced during short breath-hold apnea in healthy adults. Physiological responses of the spleen to respiratory manipulations should be considered in the measurement and interpretation of spleen volume.     

The human spleen as an erythrocyte reservoir in diving-related interventions.

Twelve subjects without and ten subjects with diving experience performed short diving-related interventions. After labeling of erythrocytes, scintigraphic measurements were continuously performed during these interventions. All interventions elicited a graduated and reproducible splenic contraction, depending on the type, severity, and duration of the interventions. The splenic contraction varied between approximately 10% for "apnea" (breath holding for 30 s) and "cold clothes" (cold and wet clothes applied on the face with no breath holding for 30 s) and approximately 30-40% for "simulated diving" (simulated breath-hold diving for 30 s), "maximal apnea" (breath holding for maximal duration), and "maximal simulated diving" (simulated breath-hold diving for maximal duration). The strongest interventions (simulated diving, maximal apnea, and maximal simulated diving) elicited modest but significant increases in hemoglobin concentration (0.1-0.3 mmol/l) and hematocrit (0.3-1%). By an indirect method, the splenic venous hematocrit was calculated to 79%. No major differences were observed between the two groups. The splenic contraction should, therefore, be included in the diving response on equal terms with bradycardia, decreased peripheral blood flow, and increased blood pressure.     

Real-time measurement of particulate matter deposition in the lung.

Air pollution and cigarette smoke are recognized health risks. A method was developed for the measurement of the deposition fraction (DF) of polydisperse particulate matter (PM) in human airways. Ten normal volunteers [three females, age range 18-67 years, mean age (SD) 43.9 (14)] made single breath exhalations after inhalation to total lung capacity. The exhaled breath was diverted to a multichannel laser diffraction chamber where the particulate profiler measured 0.3 - 1.0-microm particles. DF was inversely related to expiration flow-rate, 0.69 (0.02) at 4 l min-1 and 0.5 (0.01) at 13 l min-1, respectively (p<0.05), and was influenced by the inhalation flow-rate [0.70 (0.02) at 3 l min-1 and 0.59 (0.02) at 13 l min-1, respectively (p<0.05)], while no differences were found between nasal and oral inhalation (0.68 (0.05) versus 0.67 (0.06), p>0.05). Higher breath holding times were associated with elevated DF [0.74 (0.02) at 20 s, and 0.62 (0.05) without breath holding (p<0.01)]. When the expiratory flow was controlled and the breath hold time standardized, DF was reproducible (CV = 4.85%). PM can be measured in the exhaled breath and its DF can be quantified using a portable device. These methods may be useful in studies investigating the health effects of air pollution and tobacco smoke.     

Respiratory deposition model of an inhaled aerosol bolus

The bolus delivery method is designed to deliver a dose to the desired location in the lung, and it has the advantage of fewer side effects and a more efficient way of delivery. Based upon the lung deposition model developed for continuously inhaling aerosols of constant concentration, a mathematical model of aerosol bolus deposition is proposed. The calculated results show that the recovery depends on the bolus penetration depth, flow rate, particle size, breath holding time and bolus volume. Three sets of published experimental data with different controlling factors (particle size, flow rate and breath holding time) are adopted to make the quantitative comparisons with the calculated results. The predictions and data for the low intrinsic motion particles (～1 μm) have good agreement, as do the coarse particles in the shallow airways region. For females, the recovery was found to be consistently lower than that for males.     

Demonstration of airway closure in man.

After partial equilibration of the lung with a N2O gas mixture absorption of N2O by the pulmonary circulation results in a flow of gas into the lungs during breath holding. A bolus of 133Xe introduced at the mouth at the beginning of the breath hold is carried in by the gas flow and distributed according to regional perfusion. In three subjects, breath holding at FRC, apex-to-base distribution of a 133Xe bolud delivered by N2O absorption (Xecar) was similar to that of a bolus injected intravenously (Xeiv). Near RV however, much less of Xecar penetrated into dependent zones than expected from the distribution of Xeiv. In fact, distribution of Xecar did not differ from that of a slowly inhaled bolus. Correction for Compton scatter in the chest wall, measured in one subject, accounted only in part for the radioactivity recorded over dependent lung regions. The findings indicate that near RV some but not all of the dependent airways must be closed. Furthermore, the distribution of airway closure completely accounts for the distribution of a bolus inhaled from RV.     

Altered near‐infrared spectroscopy response to breath‐holding in patients with fibromyalgia

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain and a heightened response to pressure. Most medical researches pointed out that FM patients with endothelial dysfunction and arterial stiffness. A continuous‐wave near‐infrared spectroscopy (NIRS) system is used in present study to measure the hemodynamic changes elicited by breath‐holding task in patients with FM. Each patient completed a questionnaire survey including demographics, characteristics of body pain, associated symptoms, headache profiles and Hospital Anxiety and Depression Scale. A total of 27 FM patients and 26 health controls were enrolled. In comparison with healthy controls, patients with FM showed lower maximal and averaged change of oxyhemoglobin concentration in both the left (1.634 ±0.890 and 0.810 ±0.525 μM) and the right (1.576 ±0.897 and 0.811 ±0.601 μM) prefrontal cortex than healthy controls (P < .05 for both sides) during the breath‐holding task. In conclusion, FM is associated with altered cerebrovascular reactivity measured by NIRS and breath‐holding task, which may reflect endothelial dysfunction or arterial stiffness. Oxygenated hemoglobin concentration changes of healthy controls and FM patients.      

Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal subjects.

The purpose of this study was to determine the relationship between the three-equation diffusing capacity for carbon monoxide (DLcoSB-3EQ) and lung volume and to determine how this relationship was altered when maneuvers were immediately preceded by a deep breath. DLcoSB-3EQ maneuvers were performed in nine healthy subjects either immediately after a deep breath or after tidal breathing for 10 min. The maneuvers consisted of slow inhalation of test gas from functional residual capacity to 25, 50, 75, or 100% of the inspiratory capacity and, without breath holding, slow exhalation to residual volume. After either a deep breath or tidal breathing, we found that DLcoSB-3EQ decreased nonlinearly with decreasing lung volume. At all lung volumes, DLcoSB-3EQ was significantly greater when measured after a deep breath than after tidal breathing. This effect increased as lung volume decreased, so that the greatest difference between DLcoSB-3EQ after a deep breath and that after tidal breathing occurred at the lowest lung volume. We conclude that a deep breath or spontaneous sigh has a role in reestablishing the pathway for gas exchange during tidal breathing.     

Simulated breath-hold diving to 20 meters: cardiac performance in humans

Cardiac performance was assessed in six subjects breath-hold diving to 20 m in a hyperbaric chamber, while nonsubmersed or submersed in a thermoneutral environment. Cardiac index and systolic time intervals were obtained with impedance cardiography and intrathoracic pressure with an esophageal balloon. Breath holding at large lung volume (80% vital capacity) decreased cardiac index, probably by increasing intrathoracic pressure and thereby impeding venous return. During diving, cardiac index increased (compared with breath holding at the surface) by 35.1% in the nonsubmersed and by 29.5% in the submersed condition. This increase was attributed to a fall in intrathoracic pressure. Combination of the opposite effects of breath holding and diving to 20 m left cardiac performance unchanged during the dives (relative to the surface control). A larger intrathoracic blood redistribution probably explains a smaller reduction in intrathoracic pressure observed during submersed compared with nonsubmersed diving. Submersed breath-hold diving may entail a smaller risk of thoracic squeeze (lesser intrathoracic pressure drop) but a greater risk of overloading the central circulation (larger intrathoracic blood pooling) than simulated nonsubmersed diving.     

Respiratory deposition model of an inhaled aerosol bolus

The bolus delivery method is designed to deliver a dose to the desired location in the lung, and it has the advantage of fewer side effects and a more efficient way of delivery. Based upon the lung deposition model developed for continuously inhaling aerosols of constant concentration, a mathematical model of aerosol bolus deposition is proposed. The calculated results show that the recovery depends on the bolus penetration depth, flow rate, particle size, breath holding time and bolus volume. Three sets of published experimental data with different controlling factors (particle size, flow rate and breath holding time) are adopted to make the quantitative comparisons with the calculated results. The predictions and data for the low intrinsic motion particles (～1 μm) have good agreement, as do the coarse particles in the shallow airways region. For females, the recovery was found to be consistently lower than that for males.     

Real-time measurement of particulate matter deposition in the lung

Abstract

Air pollution and cigarette smoke are recognized health risks. A method was developed for the measurement of the deposition fraction (DF) of polydisperse particulate matter (PM) in human airways. Ten normal volunteers [three females, age range 18–67 years, mean age (SD) 43.9 (14)] made single breath exhalations after inhalation to total lung capacity. The exhaled breath was diverted to a multichannel laser diffraction chamber where the particulate profiler measured 0.3–1.0-µm particles. DF was inversely related to expiration flow-rate, 0.69 (0.02) at 4 l min^?1 and 0.5 (0.01) at 13 l min^?1, respectively (p<0.05), and was influenced by the inhalation flow-rate [0.70 (0.02) at 3 l min^?1 and 0.59 (0.02) at 13 l min^?1, respectively (p<0.05)], while no differences were found between nasal and oral inhalation (0.68 (0.05) versus 0.67 (0.06), p>0.05). Higher breath holding times were associated with elevated DF [0.74 (0.02) at 20 s, and 0.62 (0.05) without breath holding (p<0.01)]. When the expiratory flow was controlled and the breath hold time standardized, DF was reproducible (CV?=?4.85%). PM can be measured in the exhaled breath and its DF can be quantified using a portable device. These methods may be useful in studies investigating the health effects of air pollution and tobacco smoke.     

Duration of Voluntary Breath Holding and Blood Parameters

Stange's and Genci's functional tests performed at rest and during exercise and blood tests have shown that the duration of voluntary breath holding depends on appearance in the blood of hypoxia, hypercapnia, and acidosis signs only after the influence of fatigue of respiratory muscles and respiratory center has become insufficient.