End-tidal CO(2). An important parameter for a correct interpretation in functional brain studies using speech tasks

The aim was to investigate the effect of different speech tasks, i.e. recitation of prose (PR), alliteration (AR) and hexameter (HR) verses and a control task (mental arithmetic (MA) with voicing of the result on end-tidal CO2 (PETCO2), cerebral hemodynamics and oxygenation. CO2 levels in the blood are known to strongly affect cerebral blood flow. Speech changes breathing pattern and may affect CO2 levels. Measurements were performed on 24 healthy adult volunteers during the performance of the 4 tasks. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) and PETCO2 by a gas analyzer. Statistical analysis was applied to the difference between baseline before the task, 2 recitation and 5 baseline periods after the task. The 2 brain hemispheres and 4 tasks were tested separately. A significant decrease in PETCO2 was found during all 4 tasks with the smallest decrease during the MA task. During the recitation tasks (PR, AR and HR) a statistically significant (p < 0.05) decrease occurred for StO2 during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. [O2Hb] decreased significantly during PR, AR and HR in both hemispheres. [HHb] increased significantly during the AR task in the right PFC. [tHb] decreased significantly during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased and [HHb] decreased significantly during the MA task. We conclude that changes in breathing (hyperventilation) during the tasks led to lower CO2 pressure in the blood (hypocapnia), predominantly responsible for the measured changes in cerebral hemodynamics and oxygenation. In conclusion, our findings demonstrate that PETCO2 should be monitored during functional brain studies investigating speech using neuroimaging modalities, such as fNIRS, fMRI to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Vibrating Membrane Devices Deliver Aerosols More Efficient than Standard Devices: A Study in a Neonatal Upper Airway Model

Abstract Background: Aerosol therapy in preterm infants is challenging, as a very small proportion of the drug deposits in the lungs. Aim: Our aim was to compare efficiency of standard devices with newer, more efficient aerosol delivery devices. Methods: Using salbutamol as a drug marker, we studied two prototypes of the investigational eFlow(®) nebulizer for babies (PARI Pharma GmbH), a jet nebulizer (Intersurgical(®) Cirrus(®)), and a pressurized metered dose inhaler (pMDI; GSK) with a detergent-coated holding chamber (AeroChamber(®) MV) in the premature infant nose throat-model (PrINT-model) of a 32-week preterm infant (1,750 g). A filter or an impactor was placed below the infant model's "trachea" to capture the drug dose or particle size, respectively, that would have been deposited in the lung. Results: Lung dose (percentage of nominal dose) was 1.5%, 6.8%, and 18.0-20.6% for the jet nebulizer, pMDI-holding chamber, and investigational eFlow nebulizers, respectively (p<0.001). Jet nebulizer residue was 69.4% and 10.7-13.9% for the investigational eFlow nebulizers (p<0.001). Adding an elbow extension between the eFlow and the model significantly lowered lung dose (p<0.001). A breathing pattern with lower tidal volume decreased deposition in the PrINT-model and device residue (p<0.05), but did not decrease lung dose. Conclusions: In a model for infant aerosol inhalation, we confirmed low lung dose using jet nebulizers and pMDI-holding chambers, whereas newer, more specialized vibrating membrane devices, designed specifically for use in preterm infants, deliver up to 20 times more drug to the infant's lung.

Deadspace estimation from CO2 versus molar mass measurements in infants

BACKGROUND: Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. METHODS: Breath-by-breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. RESULTS: Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra-measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. CONCLUSIONS: Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants.

Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA)

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

Ventilatory response to nitrogen multiple-breath washout in infants

BACKGROUND Nitrogen multiple-breath washout (N2 MBW) using 100% oxygen (O2 ) has regained interest to assess efficiency of tracer gas clearance in, for example, children with Cystic Fibrosis (CF). However, the influence of hyperoxia on the infants' respiratory control is unclear. We assessed safety and impact on breathing pattern from hyperoxia, and if exposure to 40% O2 first induces tolerance to subsequent 100% O2 for N2 MBW. METHODS We prospectively enrolled 39 infants aged 3-57 weeks: 15 infants with CF (8 sedated for testing) and 24 healthy controls. Infants were consecutively allocated to the protocols comprising of 100% O2 or 40/100% O2 administered for 30 breaths. Lung function was measured using an ultrasonic flowmeter setup. Primary outcome was tidal volume (VT ). RESULTS None of the infants experienced apnea, desaturation, or bradycardia. Both protocols initially induced hypoventilation. VT temporarily declined in 33/39 infants across 10-25 breaths. Hypoventilation occurred independent of age, disease, and sedation. In the new 40/100% O2 protocol, VT returned to baseline during 40% O2 and remained stable during 100% O2 exposure. End-tidal carbon dioxide monitored online did not change. CONCLUSION The classical N2 MBW protocol with 100% O2 may change breathing patterns of the infants. The new protocol with 40% O2 induces hyperoxia-tolerance and does not lead to changes in breathing patterns during later N2 washout using 100% O2 . Both protocols are safe, the new protocol seems an attractive option for N2 MBW in infants. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.

Heart-lung interactions during neurally adjusted ventilatory assist

Introduction Assist in unison to the patient’s inspiratory neural effort and feedback-controlled limitation of lung distension with neurally adjusted ventilatory assist (NAVA) may reduce the negative effects of mechanical ventilation on right ventricular function. Methods Heart–lung interaction was evaluated in 10 intubated patients with impaired cardiac function using esophageal balloons, pulmonary artery catheters and echocardiography. Adequate NAVA level identified by a titration procedure to breathing pattern (NAVAal), 50% NAVAal, and 200% NAVAal and adequate pressure support (PSVal, defined clinically), 50% PSVal, and 150% PSVal were implemented at constant positive end-expiratory pressure for 20 minutes each. Results NAVAal was 3.1 ± 1.1cmH2O/μV and PSVal was 17 ± 2 cmH20. For all NAVA levels negative esophageal pressure deflections were observed during inspiration whereas this pattern was reversed during PSVal and PSVhigh. As compared to expiration, inspiratory right ventricular outflow tract velocity time integral (surrogating stroke volume) was 103 ± 4%, 109 ± 5%, and 100 ± 4% for NAVAlow, NAVAal, and NAVAhigh and 101 ± 3%, 89 ± 6%, and 83 ± 9% for PSVlow, PSVal, and PSVhigh, respectively (p < 0.001 level-mode interaction, ANOVA). Right ventricular systolic isovolumetric pressure increased from 11.0 ± 4.6 mmHg at PSVlow to 14.0 ± 4.6 mmHg at PSVhigh but remained unchanged (11.5 ± 4.7 mmHg (NAVAlow) and 10.8 ± 4.2 mmHg (NAVAhigh), level-mode interaction p = 0.005). Both indicate progressive right ventricular outflow impedance with increasing pressure support ventilation (PSV), but no change with increasing NAVA level. Conclusions Right ventricular performance is less impaired during NAVA compared to PSV as used in this study. Proposed mechanisms are preservation of cyclic intrathoracic pressure changes characteristic of spontaneous breathing and limitation of right-ventricular outflow impedance during inspiration, regardless of the NAVA level.

Alternative outcomes for the multiple breath washout in children with CF

BACKGROUND The lung clearance index (LCI) measured by multiple-breath washout (MBW) has been proposed as an outcome for clinical trials; however, MBW is time consuming and LCI can be affected by breathing pattern. We aimed to evaluate moment ratios and abbreviated LCI in school-aged children with mild-to-moderate CF lung disease. METHODS Using existing data from three studies we assessed the sensitivity of moment ratios and abbreviated LCIs to (i) detect mild-to-moderate CF lung disease and (ii) detect treatment effects after 4weeks of hypertonic saline or dornase alfa inhalation. MBW was measured by respiratory mass spectrometry using 4% "sulphur hexafluoride as a tracer gas. RESULTS Compared to the traditional LCI, moment ratios and abbreviated LCIs were similarly sensitive to detect CF lung disease. Moment ratios consistently demonstrated treatment effects, whereas abbreviated LCIs were less sensitive. CONCLUSIONS Both moment ratios and abbreviated LCI are suitable to differentiate health from disease. Sensitivity is decreased for abbreviated LCIs in interventional studies in mild CF lung disease.

Improving 4D plan quality for PBS-based liver tumour treatments by combining online image guided beam gating with rescanning.

Pencil beam scanned (PBS) proton therapy has many advantages over conventional radiotherapy, but its effectiveness for treating mobile tumours remains questionable. Gating dose delivery to the breathing pattern is a well-developed method in conventional radiotherapy for mitigating tumour-motion, but its clinical efficiency for PBS proton therapy is not yet well documented. In this study, the dosimetric benefits and the treatment efficiency of beam gating for PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data sets, which give realistic 4DCT extracting motion information from 4DMRI. The value of 4DCT(MRI) is its capability of providing not only patient geometries and deformable breathing characteristics, but also includes variations in the breathing patterns between breathing cycles. In order to monitor target motion and derive a gating signal, we simulate time-resolved beams' eye view (BEV) x-ray images as an online motion surrogate. 4DDCs have been performed using three amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived from either pre-implanted fiducial markers or the diaphragm. In addition, gating has also been simulated in combination with up to 19 times rescanning using either volumetric or layered approaches. The quality of the resulting 4DDC plans has been quantified in terms of the plan homogeneity index (HI), total treatment time and duty cycle. Results show that neither beam gating nor rescanning alone can fully retrieve the plan homogeneity of the static reference plan. Especially for variable breathing patterns, reductions of the effective duty cycle to as low as 10% have been observed with the smallest gating rescanning window (3 mm), implying that gating on its own for such cases would result in much longer treatment times. In addition, when rescanning is applied on its own, large differences between volumetric and layered rescanning have been observed as a function of increasing number of re-scans. However, once gating and rescanning is combined, HI to within 2% of the static plan could be achieved in the clinical target volume, with only moderately prolonged treatment times, irrespective of the rescanning strategy used. Moreover, these results are independent of the motion surrogate used. In conclusion, our results suggest image guided beam gating, combined with rescanning, is a feasible, effective and efficient motion mitigation approach for PBS-based liver tumour treatments.

ANÁLISE CEFALOMÉTRICA COMPARATIVA ENTRE CRIANÇAS RESPIRADORAS BUCAIS E NASAIS

Existem muitas controvérsias sobre a real interferência da respiração no crescimento craniofacial. Este estudo avaliou a possível relação da influência do padrão respiratório com as variáveis cefalométricas: 1) variáveis esqueléticas sagitais: convexidade do ponto A, profundidade facial, profundidade da maxila e comprimento do corpo mandibular; 2) variáveis esqueléticas verticais: altura facial inferior, eixo facial, cone facial, plano palatal, plano mandibular, altura facial posterior e arco mandibular; 3) variáveis dentárias: protrusão do incisivo inferior e protrusão do incisivo superior. A amostra constituiu-se de 120 crianças do sexo masculino e do sexo feminino com más-oclusões dentárias de Classe I e II-1, respiradores bucais e nasais na fase da dentadura mista e permanente, com indicação para tratamento ortodôntico. Após as avaliações ortodôntica, otorrinolaringológica e fonoaudiológica a amostra foi dividida em 2 grupos: 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras bucais e 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras nasais, sendo cada grupo divididos em 3 subgrupos nas faixas etárias: 7 a 8 anos, 9 a 10 anos e 11 a 12 anos. Após a obtenção dos resultados e a interpretação da análise estatística, foi possível concluir que: 1) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas sagitais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Convexidade pto. A: aumentada no grupo de respiração bucal, idade de 7 a 8 anos com má-oclusão Classe I. Profundidade facial : aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1. Profundidade maxila: aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1; 2) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas verticais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Cone facial: diminuída no grupo de respiração bucal, idade 9 a 10 anos com má-oclusão Classe I. Arco mandibular : diminuída no grupo de respiração bucal, idade 7 a 8 anos com má-oclusão Classe II-1.; 3) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis dentárias: constatou-se que não houve diferença estatisticamente significante para nenhuma das variáveis dentárias analisadas: protrusão do incisivo inferior e superior , não se relacionando com os padrões respiratórios (bucal e nasal).

ANÁLISE CEFALOMÉTRICA COMPARATIVA ENTRE CRIANÇAS RESPIRADORAS BUCAIS E NASAIS

Existem muitas controvérsias sobre a real interferência da respiração no crescimento craniofacial. Este estudo avaliou a possível relação da influência do padrão respiratório com as variáveis cefalométricas: 1) variáveis esqueléticas sagitais: convexidade do ponto A, profundidade facial, profundidade da maxila e comprimento do corpo mandibular; 2) variáveis esqueléticas verticais: altura facial inferior, eixo facial, cone facial, plano palatal, plano mandibular, altura facial posterior e arco mandibular; 3) variáveis dentárias: protrusão do incisivo inferior e protrusão do incisivo superior. A amostra constituiu-se de 120 crianças do sexo masculino e do sexo feminino com más-oclusões dentárias de Classe I e II-1, respiradores bucais e nasais na fase da dentadura mista e permanente, com indicação para tratamento ortodôntico. Após as avaliações ortodôntica, otorrinolaringológica e fonoaudiológica a amostra foi dividida em 2 grupos: 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras bucais e 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras nasais, sendo cada grupo divididos em 3 subgrupos nas faixas etárias: 7 a 8 anos, 9 a 10 anos e 11 a 12 anos. Após a obtenção dos resultados e a interpretação da análise estatística, foi possível concluir que: 1) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas sagitais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Convexidade pto. A: aumentada no grupo de respiração bucal, idade de 7 a 8 anos com má-oclusão Classe I. Profundidade facial : aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1. Profundidade maxila: aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1; 2) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas verticais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Cone facial: diminuída no grupo de respiração bucal, idade 9 a 10 anos com má-oclusão Classe I. Arco mandibular : diminuída no grupo de respiração bucal, idade 7 a 8 anos com má-oclusão Classe II-1.; 3) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis dentárias: constatou-se que não houve diferença estatisticamente significante para nenhuma das variáveis dentárias analisadas: protrusão do incisivo inferior e superior , não se relacionando com os padrões respiratórios (bucal e nasal).

Análise descritiva da função respiratória de adultos com fibrose quística

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Characteristics of speech following cervical spinal cord injury

The present study examined 24 individuals with either complete or incomplete injuries to the cervical spinal cord through the use of standardized assessments of dysarthria and a perceptual rating scale. Perceptual assessment revealed predominantly prosodic and phonatory disturbances, while physical impairments were common in the respiratory and laryngeal subsystems of speech production. A reduction in intelligibility and speaking rate resulted in a diminished communicative effectiveness ratio for most participants. Individuals showed a high degree of variation, with no clear relationship between lesion type and impairments present. Further investigation is required to verify the physiological nature of the respiratory and laryngeal impairments found in the present investigation and to determine the relative contributions of these to the overall presentation of speech and voice post cervical spinal cord injury (CSI).

ANÁLISE CEFALOMÉTRICA COMPARATIVA ENTRE CRIANÇAS RESPIRADORAS BUCAIS E NASAIS

Existem muitas controvérsias sobre a real interferência da respiração no crescimento craniofacial. Este estudo avaliou a possível relação da influência do padrão respiratório com as variáveis cefalométricas: 1) variáveis esqueléticas sagitais: convexidade do ponto A, profundidade facial, profundidade da maxila e comprimento do corpo mandibular; 2) variáveis esqueléticas verticais: altura facial inferior, eixo facial, cone facial, plano palatal, plano mandibular, altura facial posterior e arco mandibular; 3) variáveis dentárias: protrusão do incisivo inferior e protrusão do incisivo superior. A amostra constituiu-se de 120 crianças do sexo masculino e do sexo feminino com más-oclusões dentárias de Classe I e II-1, respiradores bucais e nasais na fase da dentadura mista e permanente, com indicação para tratamento ortodôntico. Após as avaliações ortodôntica, otorrinolaringológica e fonoaudiológica a amostra foi dividida em 2 grupos: 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras bucais e 60 crianças portadoras de más-oclusões Classe I e Classe II-1 respiradoras nasais, sendo cada grupo divididos em 3 subgrupos nas faixas etárias: 7 a 8 anos, 9 a 10 anos e 11 a 12 anos. Após a obtenção dos resultados e a interpretação da análise estatística, foi possível concluir que: 1) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas sagitais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Convexidade pto. A: aumentada no grupo de respiração bucal, idade de 7 a 8 anos com má-oclusão Classe I. Profundidade facial : aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1. Profundidade maxila: aumentada no grupo de respiração bucal, idade de 9 a 10 anos com má-oclusão Classe II-1; 2) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis esqueléticas verticais: constatou-se que houve diferença estatisticamente significante, apresentando-se as variáveis cefalométricas: Cone facial: diminuída no grupo de respiração bucal, idade 9 a 10 anos com má-oclusão Classe I. Arco mandibular : diminuída no grupo de respiração bucal, idade 7 a 8 anos com má-oclusão Classe II-1.; 3) das relações entre os padrões respiratórios (bucal e nasal) e as variáveis dentárias: constatou-se que não houve diferença estatisticamente significante para nenhuma das variáveis dentárias analisadas: protrusão do incisivo inferior e superior , não se relacionando com os padrões respiratórios (bucal e nasal).

Valoración del dolor en el paciente con trauma grave y ventilación mecánica no comunicativo

Pain is defined since 1979 by the International Association for the Study of Pain (IASP) as "unpleasant subjective, sensory and emotional experience associated with actual or potential damage of tissue", with the concept more acceptable in our days. The Intensive Care Unit (ICU) is a complex environment to assess pain, where the difficulty in communication with the patient is the biggest barrier to getting your "selfreport", which is considered the gold standard in pain assessment. Many factors alter communication with critically ill patients, as the low level of consciousness, mechanical ventilation, sedation, and the patient's own pathology, besides, there are other limitations such as excessive technology or devices that can divert professional attention to the patient's pain behavior, and lack of training and guidance for management. The multicenter study SUPPORT, it showed that 50-65% of critical patients included suffered pain, and 15% of them reported moderate to severe intensity for more than half the period of hospitalization. Critically ill patients experience pain due to high volume of potentially painful techniques applied to them during their ICU admission, emphasizing nursing care and tracheal suctioning, mobilization, wound healing and channeling of catheters and others. The underestimation of pain involves physiological and hemodynamic effects such as increased blood pressure and/or heart rate, altered breathing pattern, and psychological and anxiety. Also an increase of sedation and mechanical ventilation time and ICU stay of increasing the morbidity and mortality of critically ill patients...

The autonomic control and functional significance of the changes in heart rate associated with air breathing in the jeju, Hoplerythrinus unitaeniatus

The jeju is a teleost fish with bimodal respiration that utilizes a modified swim bladder as an air-breathing organ (ABO). Like all air-breathing fish studied to date, jeju exhibit pronounced changes in heart rate (f(H)) during air-breathing events, and it is believed that these may facilitate oxygen uptake (M-O2) from the ABO. The current study employed power spectral analysis (PSA) of f(H) patterns, coupled with instantaneous respirometry, to investigate the autonomic control of these phenomena and their functional significance for the efficacy of air breathing. The jeju obtained less than 5% of total M-O2 (M-tO2) from air breathing in normoxia at 26 degrees C, and PSA of beat-to-beat variability in fH revealed a pattern similar to that of unimodal water-breathing fish. In deep aquatic hypoxia (water P-O2=1 kPa) the jeju increased the frequency of air breathing (f(AB)) tenfold and maintained M-tO2 unchanged from normoxia. This was associated with a significant increase in heart rate variability (HRV), each air breath (AB) being preceded by a brief bradycardia and then followed by a brief tachycardia. These f(H) changes are qualitatively similar to those associated with breathing in unimodal air-breathing vertebrates. Within 20 heartbeats after the AB, however, a beat-to-beat variability in f(H) typical of water-breathing fish was re-established. Pharmacological blockade revealed that both adrenergic and cholinergic tone increased simultaneously prior to each AB, and then decreased after it. However, modulation of inhibitory cholinergic tone was responsible for the major proportion of HRV, including the precise beat-to-beat modulation of f(H) around each AB. Pharmacological blockade of all variations in f(H) associated with air breathing in deep hypoxia did not, however, have a significant effect upon f(AB) or the regulation of M-tO2. Thus, the functional significance of the profound HRV during air breathing remains a mystery.