Hyperoxia-induced stepwise reduction in blood flow through intrapulmonary, but not intracardiac, shunt during exercise.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) (QIPAVA) increases during exercise breathing air, but it has been proposed that QIPAVA is reduced during exercise while breathing a fraction of inspired oxygen ([Formula: see text]) of 1.00. It has been argued that the reduction in saline contrast bubbles through IPAVA is due to altered in vivo microbubble dynamics with hyperoxia reducing bubble stability, rather than closure of IPAVA. To definitively determine whether breathing hyperoxia decreases saline contrast bubble stability in vivo, the present study included individuals with and without patent foramen ovale (PFO) to determine if hyperoxia also eliminates left heart contrast in people with an intracardiac right-to-left shunt. Thirty-two participants consisted of 16 without a PFO; 8 females, 8 with a PFO; 4 females, and 8 with late-appearing left-sided contrast (4 females) completed five, 4-min bouts of constant-load cycle ergometer exercise (males: 250 W, females: 175 W), breathing an [Formula: see text] = 0.21, 0.40, 0.60, 0.80, and 1.00 in a balanced Latin Squares design. QIPAVA was assessed at rest and 3 min into each exercise bout via transthoracic saline contrast echocardiography and our previously used bubble scoring system. Bubble scores at [Formula: see text]= 0.21, 0.40, and 0.60 were unchanged and significantly greater than at [Formula: see text]= 0.80 and 1.00 in those without a PFO. Participants with a PFO had greater bubble scores at [Formula: see text]= 1.00 than those without a PFO. These data suggest that hyperoxia-induced decreases in QIPAVA during exercise occur when [Formula: see text] ≥ 0.80 and is not a result of altered in vivo microbubble dynamics supporting the idea that hyperoxia closes QIPAVA.

Pulmonary diffusing capacity to nitric oxide and carbon monoxide during exercise and in the supine position: a test-retest reliability study.

NEW FINDINGS: What is the central question in this study? How reliable is the combined measurement of the pulmonary diffusing capacity to carbon monoxide and nitric oxide (DLCO/NO ) during exercise and in the resting supine position, respectively? What is the main finding and its importance? The DLCO/NO technique is reliable with a very low day-to-day variability both during exercise and in the resting supine position, and may thus provide a useful physiological outcome that reflects the alveolar-capillary reserve in humans. ABSTRACT: DLCO/NO , the combined single-breath measurement of the diffusing capacity to carbon monoxide (DLCO ) and nitric oxide (DLNO ) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar-capillary reserve. In the present study, we investigated the between-day test-retest reliability of DLCO/NO -based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test-retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar-capillary reserve, both during exercise and in the supine position.

Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

PURPOSE: To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment. METHODS: Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra. RESULTS: Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances. CONCLUSION: Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

Arterial Blood Gas and Rotational Thromboelastometry Parameters in Healthy Rescuers Incidentally Exposed to Nitroglycerin, Nitrogen Compounds, and Combustion Products.

INTRODUCTION: Acute exposure to nitrogen compounds combined with a massive inhalation of air pollutants can influence respiratory and cardiovascular symptoms and coagulation abnormalities in accidentally exposed healthy adults during cave detonation operations. METHODS: Italian alpine and cave rescuers widened a cave in the Abisso Luca Kralj in Trieste, Italy. Volunteers inside the cave were accidentally exposed to the fumes from an uncontrolled detonation of blasting gelatin microcharges. We performed a retrospective cohort study on the clinical data, arterial blood gas analysis, and rotational thromboelastometry parameters from the rescuers involved in the accident. RESULTS: Ninety-three healthy rescuers were involved in the uncontrolled detonation: 47 volunteers handled a mixture of nitrogen compounds (blaster group), and 46 volunteers did not (nonblaster group). After the accident, statistically significant differences (P<0.05) in arterial blood gas values were observed between the groups, with a pattern of mild respiratory acidosis with hypercapnia in the nonblaster group and severe mixed acid-base disorder with hypoxia and hypercapnia in the blaster group. Mild hyperfibrinolysis was observed in 44 volunteers in the blaster group, as were associated bleeding symptoms in 34 volunteers; no significant coagulation modifications were recorded in the nonblaster group. CONCLUSIONS: Respiratory acidosis with hypoxia, hypercapnia, a compensatory metabolic response, and mild hyperfibrinolysis were probably related to the combined effect of nitrogen compounds and the inhaled toxic products of detonation. Therefore, each element exerts a determinant effect on promoting the biological toxicity of the others.

Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized-control cross-over trial.

KEY POINTS: Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on V̇E / V̇CO2 , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD. ABSTRACT: Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO2 production ( V̇E / V̇CO2 ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower V̇E / V̇CO2 and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV1  =  89 ± 11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs. 1.53 ± 0.10 L·min-1 , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced V̇E / V̇CO2 by 3.8 ± 4.2 units (P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units (P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced V̇E / V̇CO2 and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased V̇E / V̇CO2 , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.

Temporal changes in pulmonary gas exchange efficiency when breath-hold diving below residual volume.

NEW FINDINGS: What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive? What is the main finding and its importance? Breath-hold diving, to depths below residual volume, is associated with acute impairments in pulmonary gas exchange, which typically resolve within 2.5 hours. These data provide new insight into the behaviour of the lungs and pulmonary vasculature following deep diving. ABSTRACT: Breath-hold diving involves highly integrative and extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. Over two diving training camps (Study 1 and 2), 25 breath-hold divers (recreational to world-champion) performed 66 dives to 57 ± 20 m (range: 18-117 m). Using the deepest dive from each diver, temporal changes in cardiopulmonary function were assessed using non-invasive pulmonary gas exchange (indexed via the O2 deficit), ultrasound B-line scores, lung compliance and pulmonary haemodynamics at baseline and following the dive. Hydrostatically induced lung compression was quantified in Study 2, using spirometry and lung volume measurement, enabling each dive to be categorized by its residual volume (RV)-equivalent depth. From both studies, pulmonary gas exchange inefficiency - defined as an increase in O2 deficit - was related to the depth of the dive (r2  = 0.345; P < 0.001), with dives associated with lung squeeze symptoms exhibiting the greatest deficits. In Study 1, although B-lines doubled from baseline (P = 0.027), cardiac output and pulmonary artery systolic pressure were unchanged post-dive. In Study 2, dives with lung compression to ≤RV had higher O2 deficits at 9 min, compared to dives that did not exceed RV (24 ± 25 vs. 5 ± 8 mmHg; P = 0.021). The physiological significance of a small increase in estimated lung compliance post-dive (via decreased and increased/unaltered airway resistance and reactance, respectively) remains equivocal. Following deep dives, the current study highlights an integrated link between hydrostatically induced lung compression and transient impairments in pulmonary gas exchange efficiency.

Availability of portable capnometers in children with tracheostomy.

BACKGROUND: A capnometer is a noninvasive monitor that is used to assess patients' respiratory status. This study was performed to evaluate the availability of a portable capnometer in children with tracheostomy. METHODS: This retrospective study included children with tracheostomy who were treated at the Osaka Women's and Children's Hospital Osaka, Japan, from 1 September 2018 to 31 October 2019. We assessed the correlation between the partial pressure of venous carbon dioxide (PvCO2 ) and end-tidal carbon dioxide tension (EtCO2 ) using a portable capnometer (EMMA; Masimo, Irvine, CA, USA). RESULTS: Nine infants and 43 simultaneous PvCO2 -EtCO2 pairs were analyzed. The correlation coefficient of these pairs was 0.87 (95% confidence interval, 0.77-0.93; P < 0.001). The Bland-Altman plot showed that EtCO2 was on average 10.0 mmHg lower than its paired PvCO2 value (95% limits of agreement, 1.0-19.1). The difference between PvCO2 and EtCO2 was significantly greater in patients on ventilators. CONCLUSIONS: The portable capnometer evaluated in this study (EMMA) was readily available and useful for assessment of the respiratory condition in children with tracheostomy.

Influence of high affinity haemoglobin on the response to normoxic and hypoxic exercise.

KEY POINTS: Theoretical models suggest there is no benefit of high affinity haemoglobin to preserve maximal oxygen uptake in acute hypoxia but the comparative biology literature has many examples of species that are evolutionarily adapted to hypoxia and have high affinity haemoglobin. We studied humans with high affinity haemoglobin and compensatory polycythaemia. These subjects performed maximal exercise tests in normoxia and hypoxia to determine how their altered haemoglobin affinity impacts hypoxic exercise tolerance. The high affinity haemoglobin participants demonstrated an attenuated decline in maximal aerobic capacity in acute hypoxia. Those with high affinity haemoglobin had no worsening of pulmonary gas exchange during hypoxic exercise but had greater lactate and lower pH than controls for all exercise bouts. High affinity haemoglobin and compensatory polycythaemia mitigated the decline in exercise performance in acute hypoxia through a higher arterial oxygen content and an unchanged pulmonary gas exchange. ABSTRACT: The longstanding dogma is that humans exhibit an acute reduction in haemoglobin (Hb) binding affinity for oxygen that facilitates adaptation to moderate hypoxia. However, many animals have adapted to high altitude through enhanced Hb binding affinity for oxygen. The objective of the study was to determine whether high affinity haemoglobin (HAH) affects maximal and submaximal exercise capacity. To accomplish this, we recruited individuals (n = 11, n = 8 females) with HAH (P50  = 16 ± 1 mmHg), had them perform normoxic and acute hypoxic (15% inspired oxygen) maximal exercise tests, and then compared their results to matched controls (P50  = 26 ± 1, n = 14, n = 8 females). Cardiorespiratory and arterial blood gases were collected throughout both exercise tests. Despite no difference in end-exercise arterial oxygen tension in hypoxia (59 ± 6 vs. 59 ± 9 mmHg for controls and HAH, respectively), the HAH subjects' oxyhaemoglobin saturation ( Sa,O2 ) was ∼7% higher. Those with HAH had an attenuated decline in maximal oxygen uptake ( V̇O2max ) (4 ± 5% vs. 12 ± %, p < 0.001) in hypoxia and the change in V̇O2max between trials was related to the change in SaO2 (r = -0.75, p < 0.0001). Compared to normoxia, the controls' alveolar-to-arterial oxygen gradient significantly increased during hypoxic exercise, whereas pulmonary gas exchange in HAH subjects was unchanged between the two exercise trials. However, arterial lactate was significantly higher and arterial pH significantly lower in the HAH subjects for both exercise trials. We conclude that HAH attenuates the decline in maximal aerobic capacity and preserves pulmonary gas exchange during acute hypoxic exercise. Our data support the comparative biology literature indicating that HAH is a positive adaptation to acute hypoxia.

Individualised positive end-expiratory pressure guided by electrical impedance tomography for robot-assisted laparoscopic radical prostatectomy: a prospective, randomised controlled clinical trial.

BACKGROUND: Robot-assisted laparoscopic radical prostatectomy requires general anaesthesia, extreme Trendelenburg positioning and capnoperitoneum. Together these promote impaired pulmonary gas exchange caused by atelectasis and may contribute to postoperative pulmonary complications. In morbidly obese patients, a recruitment manoeuvre (RM) followed by individualised PEEP improves intraoperative oxygenation and end-expiratory lung volume (EELV). We hypothesised that individualised PEEP with initial RM similarly improves intraoperative oxygenation and EELV in non-obese individuals undergoing robot-assisted prostatectomy. METHODS: Forty males (age, 49-76 yr; BMI <30 kg m-2) undergoing prostatectomy received volume-controlled ventilation (tidal volume 8 ml kg-1 predicted body weight). Participants were randomised to either (1) RM followed by individualised PEEP (RM/PEEPIND) optimised using electrical impedance tomography or (2) no RM with 5 cm H2O PEEP. The primary outcome was the ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2/Fio2) before the last RM before extubation. Secondary outcomes included regional ventilation distribution and EELV which were measured before, during, and after anaesthesia. The cardiovascular effects of RM/PEEPIND were also assessed. RESULTS: In 20 males randomised to RM/PEEPIND, the median PEEPIND was 14 cm H2O [inter-quartile range, 8-20]. The Pao2/Fio2 was 10.0 kPa higher with RM/PEEPIND before extubation (95% confidence interval [CI], 2.6-17.3 kPa; P=0.001). RM/PEEPIND increased end-expiratory lung volume by 1.49 L (95% CI, 1.09-1.89 L; P<0.001). RM/PEEPIND also improved the regional ventilation of dependent lung regions. Vasopressor and fluid therapy was similar between groups, although 13 patients randomised to RM/PEEPIND required pharmacological therapy for bradycardia. CONCLUSION: In non-obese males, an individualised ventilation strategy improved intraoperative oxygenation, which was associated with higher end-expiratory lung volumes during robot-assisted laparoscopic prostatectomy. CLINICAL TRIAL REGISTRATION: DRKS00004199 (German clinical trials registry).

Children with uncontrolled asthma and significant reversibility might show hypoxaemia.

Asthmatic children free of exacerbation with airway obstruction may have low partial pressure of oxygen (PaO2) which can be a marker for future risk, but PaO2 is scarcely measured during pulmonary function testing. We prospectively included asthmatic children with airway obstruction referred for pulmonary function testing, including blood gas analysis (n = 51). Hypoxaemia, defined as a value lower than - 2 z-score, was present in 15 (29%) children, and 37 (72%) children had a significant reversibility after bronchodilator administration. The multivariable model showed a positive influence of baseline forced expiratory volume in 1 s (FEV1) on PaO2 (ß coefficient 0.69, [95% CI: 0.07; 1.30]; P = 0.03), whereas uncontrolled asthma and FEV1 reversibility negatively influenced it (ß coefficient - 1.59 [95% CI: - 2.74; - 0.44]; P = 0.01; and - 0.07 [95% CI: - 0.13; - 0.02]; P = 0.01, respectively). As a consequence, children with uncontrolled symptoms of asthma and FEV1 reversibility ≥ 12% were significantly more at risk of having hypoxaemia compared to children with well/partly controlled asthma or no significant reversibility of FEV1.Conclusion: Among obstructive asthmatic children without current exacerbation, hypoxaemia is more likely to be seen in children with uncontrolled asthma and a significant post-bronchodilator FEV1 reversibility, in favour of different pathophysiology and treatment requirements of their airway obstruction.What is Known:• Recommendations are to treat asthmatic children in order to control respiratory symptom and maintain normal pulmonary function.• Asthmatic children free of exacerbation may have different pathophysiology for airway obstruction (central, peripheral, inflammatory, spasticity, remodelling) and should be treated according the pathophysiology of their airway disease.What is New:• In obstructive asthmatic children free of current exacerbation, the presence of hypoxaemia (ventilation-perfusion mismatch) is influenced by asthma control and post-bronchodilator reversibility, independently of the level of baseline airway obstruction.• The presence of hypoxaemia in obstructive asthmatic children free of current exacerbation can be highly suspected by the composite index "uncontrolled asthma + FEV1reversibility ≥ 12%" which may guide treatment.

Non-invasive screening using ventilatory gas analysis to distinguish between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Clinical presentations associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) at rest are highly similar. Differentiating between CTEPH and PAH using non-invasive techniques remains challenging. Thus, we examined whether analysis of ventilatory gas in response to postural changes can be useful as a non-invasive screening method for pulmonary hypertension (PH), and help differentiate CTEPH from PAH. METHODS: We prospectively enrolled 90 patients with suspected PH and performed right heart catheterization, ventilation/perfusion scan and ventilatory gas analysis. Various pulmonary function parameters were examined in the supine and sitting postures, and postural changes were calculated (Δ(supine - sitting)). RESULTS: In total, 25 patients with newly diagnosed PAH, 40 patients with newly diagnosed CTEPH and 25 non-PH patients were included. ΔEnd-tidal CO2 pressure (PET CO2 ) was significantly lower in patients with CTEPH and PAH than in non-PH patients (both P < 0.001). ΔPET CO2 < 0 mm Hg could effectively differentiate PH from non-PH (area under the curve (AUC) = 0.969, sensitivity = 89%, specificity = 100%). Postural change from sitting to supine significantly increased the ratio of ventilation to CO2 production (VE/VCO2 ) in the CTEPH group (P < 0.001). By contrast, VE/VCO2 significantly decreased in the PAH group (P = 0.001). Notably, CTEPH presented with higher ΔVE/VCO2 than PAH, although no differences were observed in haemodynamic and echocardiographic parameters between the two groups (P < 0.001). Furthermore, ΔVE/VCO2 > 0.8 could effectively differentiate CTEPH from PAH (AUC = 0.849, sensitivity = 78%, specificity = 88%). CONCLUSION: Postural changes in ventilatory gas analysis are useful as a non-invasive bedside evaluation to screen for the presence of PH and distinguish between CTEPH and PAH.

Precapillary pulmonary gas exchange is similar for oxygen and inert gases.

KEY POINTS: Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1 cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7 mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. ABSTRACT: Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1 cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F = (P - D)/(P - A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n = 12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P = 88.6 ± 18.1%; P = 0.03) and ethane (D/P = 90.6 ± 16.0%; P = 0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1 ± 6.8% vs. 69.0 ± 4.9%; P = 0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12 ± 0.19, 0.12 ± 0.20 and 0.19 ± 0.26, respectively; P = 0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.

Intra-pulmonary arteriovenous anastomoses and pulmonary gas exchange: evaluation by microspheres, contrast echocardiography and inert gas elimination.

KEY POINTS: Imaging techniques such as contrast echocardiography suggest that anatomical intra-pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung. To evaluate this discrepancy, we compared anatomical shunt with 25-µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET). Intra-pulmonary shunt measured by 25-µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt. A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. ABSTRACT: The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra-pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right-to-left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25-µm microspheres and compared the results to contrast echocardiography and MIGET-determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg-1  min-1 i.v. dopamine, (3) 10 µg kg-1  min-1 i.v. dobutamine, and (4) following creation of an intra-atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25-µm microspheres recovered in systemic arterial blood. Ventilation-perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25-µm microspheres. Across all conditions, anatomical shunt measured by 25-µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%, P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60, P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22-48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25-µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.

Bronchopulmonary dysplasia: Rationale for a pathophysiological rather than treatment based approach to diagnosis.

Bronchopulmonary dysplasia (BPD), also known as Chronic Lung Disease (CLD), is a chronic respiratory condition of prematurity with potential life-long consequences for respiratory well-being. BPD was first described by Northway in 1967, when the mean gestation of preterm infants with BPD was 34 weeks' postmenstrual age (PMA). Survival of preterm infants at lower gestational ages has increased steadily since 1967 associated with marked improvements in respiratory management of respiratory distress syndrome. Currently, BPD develops in approximately 45 % of all infants born extremely preterm (Stoll et al., 2015). These smaller and more immature babies are born during the late canalicular or early saccular period of lung development. Not surprisingly, the pathophysiology of BPD also evolved since classical BPD was described. As the nature and our understanding of BPD evolved, so too the definitions and classification of BPD changed over time. These differing and ever-changing definitions hamper clinical benchmarking as they are interpreted and applied inconsistently, and define BPD and its severity by non-standardised treatments rather than independent evaluations of structure or function. A standardised, unambiguous definition and classification of BPD is essential for evaluation and improvement in clinical practice, both within an individual unit, as well as across and between neonatal networks. The determination and implementation of diagnostic criteria and severity classification that is standardised, globally applicable, and that has prognostic utility for clinical outcomes and guidance of ongoing respiratory management remain of utmost importance. This review describes the evolution of BPD definitions, evaluates the benefits and limitations of each approach, and discusses alternative approaches that may improve the functional assessment of BPD severity.

Effects of 12 and 17 cmH2O positive end-expiratory pressure applied after alveolar recruitment maneuver on pulmonary gas exchange and compliance in isoflurane-anesthetized horses.

OBJECTIVE: To compare static compliance (Cst) and alveolar-arterial oxygen tension difference [P(a-a)O2] between positive end-expiratory pressures (PEEP) of 7, 12 and 17 cmH2O applied after an alveolar recruitment maneuver (RM) in isoflurane-anesthetized horses. STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: A group of 30 healthy adult horses undergoing arthroscopic surgery. METHODS: Animals in dorsal recumbency and mechanically ventilated with a tidal volume of 14 mL kg-1 and 7 cmH2O PEEP (control; n = 6) were subjected to an RM by increasing PEEP from 7 to 22 cmH2O in 5 cmH2O increments at 5 minute intervals, and then decreased similarly to PEEP of 17 (RM17; n = 8), 12 (RM12; n = 8) or 7 cmH2O (RM7; n = 8). Cst and P(a-a)O2 were assessed prior to (baseline) and after the RM at 5, 10, 15, 20, 40, 60 and 80 minutes after achieving each target PEEP, and during recovery from anesthesia. RESULTS: Post-RM improvements on P(a-a)O2 were maintained (baseline versus 80 minutes) in RM12 [216 ± 77 mmHg (28.8 ± 10.3 kPa) versus 194 ± 39 mmHg (25.9 ± 5.2 kPa)] and RM17 [180 ± 86 mmHg (24.0 ± 11.6 kPa) versus 136 ± 75 mmHg [18.2 ± 10.0 kPa]). The improvements on Cst were maintained only in RM12 (0.80 ± 0.13 versus 0.98 ± 0.13 mL cmH2O-1 kg-1). No such improvements were observed in RM7 and control. No significant differences were observed between groups during recovery from anesthesia. CONCLUSIONS: and clinical relevance The 12 and 17 cmH2O PEEP can be used to maintain the improvements on P(a-a)O2 obtained after an RM. Only 12 cmH2O PEEP maintained the post-RM increase on Cst. Such variables were not influenced by the 7 cmH2O PEEP.

Afferent neural feedback overrides the modulating effects of arousal, hypercapnia and hypoxaemia on neonatal cardiorespiratory control.

KEY POINTS: Evidence obtained at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for the establishment of adequate ventilation at birth. As a result of the irreversible nature of the vagal ablation studies performed to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apnoeas and hypoxaemia and hypercarbia were observed, necessitating the termination of perineural blockade. Respiratory depression and apnoeas were independent of sleep state. We demonstrate that profound apnoeas and life-threatening respiratory failure in vagally denervated animals do not result from a lack of arousal or hypoxaemia. A change in sleep state and concomitant respiratory depression result from a lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. ABSTRACT: Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apnoeas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during the early postnatal period. Seven lambs were instrumented during the first 48 h of life to record/analyse sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Postoperatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 min. Compared to baseline values, pHa , Pao2 and Sao2 decreased and Paco2 increased during perineural blockade (P < 0.05). Four of seven animals exhibited apnoeas of ≥20 s requiring the immediate termination of perineural blockade. Breathing rates decreased from the baseline value of 53 ± 12 to 24 ± 20 breaths min-1 during blockade despite an increased Paco2 (P < 0.001). Following blockade, breathing patterns returned to baseline values despite marked hypocapnia ( Paco2 33 ± 3 torr; P = 0.03). Respiratory depression and apnoeas were independent of sleep states. The present study provides the much needed physiological evidence indicating that profound apnoeas and life-threatening respiratory failure in vagally denervated animals do not result from a lack of arousal or hypoxaemia. Rather, a change in sleep state and concomitant respiratory depression result from a lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period.

Comparison between neurally-assisted, controlled, and physiologically variable ventilation in healthy rabbits.

BACKGROUND: Various ventilation strategies have been proposed to reduce ventilation-induced lung injury that occurs even in individuals with healthy lungs. We compared new modalities based on an individualised physiological variable ventilation model to a conventional pressure-controlled mode. METHODS: Rabbits were anaesthetised and ventilated for up to 7 h using pressure-controlled ventilation with (Group PCS, n=10), and without (Group PC, n=10) regular sighs. Variable ventilation in the other two groups was achieved via a pre-recorded spontaneous breathing pattern [Group physiologically variable ventilation (PVV), n=10] or triggered by the electrical activity of the diaphragm [Group neurally adjusted ventilation assist (NAVA), n=9]. Respiratory elastance, haemodynamic profile, and gas exchange were assessed throughout the ventilation period. Cellular profile, cytokine content of bronchoalveolar lavage fluid, and wet-to-dry lung weight ratio (W/D) were determined after protocol completion. Lung injury scores were obtained from histological analysis. RESULTS: Marked deteriorations in elastance were observed (median and 95% confidence interval) in Group PC [48.6 (22)% increase from baseline], while no changes were detected in Groups PCS [3.6 (8.1)%], PVV [18.7 (13.2)%], and NAVA [-1.4 (12.2)%]. In comparison with Group PC, Group PVV had a lower lung injury score [0.29 (0.02) compared with 0.36 (0.05), P<0.05] and W/D ratio [5.6 (0.1) compared with 6.2 (0.3), P<0.05]. There was no difference in blood gas, haemodynamic, or inflammatory parameters between the groups. CONCLUSIONS: Individualised PVV based on a pre-recorded spontaneous breathing pattern provides adequate gas exchange and promotes a level of lung protection. This ventilation modality could be of benefit during prolonged anaesthesia, in which assisted ventilation is not possible because of the absence of a respiratory drive.

Effects on the pulmonary hemodynamics and gas exchange with a speed modulated right ventricular assist rotary blood pump: a numerical study.

Rotary blood pumps (RBPs) are the newest generation of ventricular assist devices. Although their continuous flow characteristics have been accepted widely, more and more research has focused on the pulsatile modulation of RBPs in an attempt to provide better perfusion. In this study, we investigated the effects of an axial RBP serving as the right ventricular assist device on pulmonary hemodynamics and gas exchange using a numerical method with a complete cardiovascular model along with airway mechanics and a gas exchange model. The RBP runs in both constant speed and synchronized pulsatile modes using speed modulation. Hemodynamics and airway O2 and CO2 partial pressures were obtained under normal physiological conditions, and right ventricle failure conditions with or without RBP. Our results showed that the pulsatile mode of the RBP could support right ventricular assist to restore most hemodynamics. Using speed modulation, both pulmonary arterial pressure and flow pulsatility were increased, while there was only very little effect on alveolar O2 and CO2 partial pressures. This study could provide basic insight into the influence of pulmonary hemodynamics and gas exchange with speed modulated right ventricular assist RBPs, which is concerned when designing their pulsatile control methods.

Assessing Ventilatory Threshold in Individuals With Motor-Complete Spinal Cord Injury.

OBJECTIVE: To assess the feasibility of measuring ventilatory threshold (VT) in higher-level motor-complete spinal cord injury (SCI) using 4 different analysis methods based on noninvasive gas exchange. DESIGN: Observational. SETTING: Laboratory testing. PARTICIPANTS: Individuals with C4-T6 motor-complete SCI (16 paraplegia, 22 tetraplegia; American Spinal Injury Association Impairment Scale A/B; 42±10 years old). INTERVENTIONS: Not applicable. MAIN OUTCOME: VT from a graded arm cycling test to volitional exhaustion using 4 methods: ventilatory equivalents, excess CO2, V-slope, and combined method. RESULTS: VT could be identified in all individuals with paraplegia, but in only 68% of individuals with tetraplegia. Individuals without observable VT completed the graded exercise test with lower ventilatory rate, peak power output, and peak oxygen consumption (Vo2peak) (all P<.05), compared to those with a detectable VT. Bland-Altman plots indicate minimal bias between methods (range: 0.01-0.03 L/min), with 95% limits of agreement of the difference within 0.25 L/min. Absolute V.o2 at VT with individual methods were all correlated to peak power output (r>0.74; P<.01) and Vo2peak (r>0.91; P<.01), with negligible differences between methods. CONCLUSIONS: The assessment of VT is a feasible alternative to peak exercise testing for aerobic fitness in individuals with higher-level, motor-complete SCI, although care should be taken when interpreting VT in individuals with tetraplegia who have lower cardiorespiratory fitness and lower peak power outputs.