Changes In Pulmonary Gas Exchange Research Articles

Quantifying Regional Radiation-Induced Lung Injury in Patients Using Hyperpolarized 129Xe Gas Exchange Magnetic Resonance Imaging

PurposeRadiation-induced lung injury (RILI) has been shown to alter regional ventilation and perfusion in the lung. However, changes in regional pulmonary gas exchange have not previously been measured. MethodsTen patients receiving conventional radiation therapy (RT) for lung cancer underwent pre-RT and 3-month post-RT MRI using an established hyperpolarized-129Xe gas exchange technique to map lung function. Four patients underwent an additional 8-month post-RT MRI. The MR signal from inhaled xenon is measured in three pulmonary compartments: the lung airspaces, the alveolar membrane tissue, and the pulmonary capillaries (interacting with red blood cells, RBCs). Thoracic 1H MRI scans were acquired, and deformable registration was used to transfer 129Xe functional maps to the RT planning CT. The RT-associated changes in ventilation, membrane uptake, and RBC transfer, were computed as a function of regional lung dose (equivalent dose in 2-Gy fractions, EQD2). Pearson correlation and t-tests were used to determine statistical significance, and weighted sum of squares linear regression subsequently characterized the dose-dependence of each functional component. Pulmonary function testing (PFT) metrics forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were also acquired at each timepoint. ResultsCompared to pre-RT baseline, 3-month post-RT ventilation decreased by an average of -0.24±0.05 %/Gy (ρ=-0.88; P<.001), membrane uptake increased by 0.69±0.14 %/Gy (ρ=0.94; P<.001), and RBC transfer decreased by -0.41±0.06 %/Gy (ρ=-0.92; P<.001). Membrane uptake maintained a strong positive correlation with regional dose at 8 months post-RT, demonstrating an increase of 0.73±0.11 %/Gy (ρ=0.92; P=.006). Changes in membrane uptake and RBC transfer appeared greater in magnitude (%/Gy) for subjects with low heterogeneity in their baseline lung function. An increase in whole-lung membrane uptake showed moderate correlation with decreases in FVC (ρ=-0.50; P=0.17) and DLCO (ρ=-0.44; P=0.23), with neither correlation reaching statistical significance. ConclusionHyperpolarized-129Xe MRI measured and quantified regional, RT-associated, dose-dependent changes in pulmonary gas exchange. This tool could enable future work to improve our understanding and management of RILI.

Oxygen uptake kinetics and ventilatory and metabolic parameters do not differ between moderate‐intensity front crawl and breaststroke swimming

Pulmonary oxygen uptake (V˙O2) kinetics have been well studied during land‐based exercise. However, less is known about V˙O2 kinetics during swimming exercise and comparisons between strokes is non‐existent. We aimed to characterize and compare the V˙O2 kinetics, ventilatory,e and metabolic response to constant velocity moderate‐intensity freely breathing front crawl (FC) and breaststroke (BR) swimming in a swimming flume. These two strokes reflect predominantly upper body versus lower body modes of swimming locomotion, respectively. Eight trained swimmers (4 females, 20 ± 1 years, 1.74 ± 0.06 m; 66.8 ± 6.3 kg) attended 5–6 laboratory‐based swimming sessions. The first two trials determined FC and BR V˙O2max and the ventilatory threshold (VT), respectively, during progressive intensity swimming to the limit of tolerance. Subsequent trials involved counterbalanced FC and BR transitions from prone floating to constant velocity moderate‐intensity swimming at 80% of the velocity at VT (vVT), separated by 30‐min recovery. Breath‐by‐breath changes in pulmonary gas exchange and ventilation were measured continuously using a snorkel and aquatic metabolic cart system. The ventilatory and metabolic responses were similar (p > 0.05) between strokes during maximal velocity swimming, however, vVT and maximal velocity were slower (p < 0.05) during BR . During moderate‐intensity swimming, V˙O2 kinetics, ventilatory and metabolic parameters were similar (p > 0.05) between strokes. In conclusion, when breathing ad libitum, V˙O2 kinetics during moderate‐intensity constant velocity swimming, and ventilatory and metabolic responses during moderate‐intensity and maximal velocity swimming, are similar between FC and BR strokes.

Development of a fibre optic oxygen sensor for respiratory monitoring in the intensive care unit

Arterial oxygen tension is commonly measured by means of intermittent arterial gas sampling. This technique is unable to detect within-breath oxygen tension changes that may be observed in mechanically ventilated patients, especially in the presence of lung injury. Moreover, it may not afford sufficient time resolution to detect potentially injurious settings of the mechanical ventilation itself. Continuous and rapid arterial oxygen tension measurement could detect within-breath changes in pulmonary gas exchange and offer clinically important feedback for the management of mechanical ventilation therapy in real time. We developed a novel fibre optic intravascular oxygen tension sensor, measured its fast response time in vitro, tested its blood clotting resistance over a period of 24 hours, and its capacity to measure arterial oxygen tension in vivo in a pig model of uninjured lung. This short communication will review the main steps of this collaborative project’s progress to date, highlighting the technology’s strengths, together with future potential for translation to a clinical scenario.

Temperature and dehydration effects on metabolism, water uptake and the partitioning between respiratory and cutaneous evaporative water loss in a terrestrial toad.

Terrestrial anurans often experience fluctuations in body temperature and hydration state, which are known to influence evaporative water loss through the skin (EWLSkin) and lungs (EWLResp). These effects arise from associated changes in skin permeability, metabolism and lung ventilation. Herein, we determined the rates of EWLSkin and EWLResp in the terrestrial toad Rhinella diptycha at different temperatures and hydration states. We measured oxygen uptake rates to verify whether alterations in the partitioning between EWLSkin and EWLResp were associated with metabolism-induced changes in pulmonary gas exchange. We also measured the influence of hydration and temperature on water uptake (WU) through the skin. Finally, as estimates of skin resistance to evaporation (Rs) are usually inferred from total evaporative water loss (EWLTotal), under the assumption of negligible EWLResp, we calculated the potential error in accepting this assumption for different temperature and hydration states. EWLSkin and EWLResp increased with temperature, but this response was greater for EWLResp, which was attributed to the temperature-induced elevation in metabolism and lung ventilation. Dehydration caused a decrease in the relative contribution of EWLSkin to EWLTotal, mirrored by the concurrent increase in the contribution of EWLResp, at all temperatures. Thus, Rs increased with dehydration. WU rates were dictated by dehydration with little influence of temperature. The partitioning between EWLSkin and EWLResp was affected by both temperature and hydration state and, under some conditions, considering EWLResp as negligible led to significant errors in the assessment of skin resistance to evaporation.

Characterizing cerebral and locomotor muscle oxygenation to incremental ramp exercise in healthy children: relationship with pulmonary gas exchange.

To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental exercise in children and to assess the interrelationship with the pulmonary gas exchange responses. Eighteen children (9 boys, 9 girls) (mean age 10.9±1.0years) performed incremental cycle ramp exercise to exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were expressed as functions of oxygen uptake (VO2) and breakpoints were detected by means of double linear model analysis. The respiratory compensation point (RCP) was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared and correlated to RCP. The subjects reached peak power output of 105±18W and VO2peak of 43.5±7.0mlmin-1kg-1. Cerebral O2Hb increased to an intensity of 89.4±5.5%VO2peak, where a breakpoint occurred at which cerebral O2Hb started to decrease. Cerebral HHb increased slightly to 88.1±4.8%VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5±4.8%VO2peak where a leveling-off occurred. RCP occurred at 89.3±4.3%VO2peak. The breakpoints and RCP did not differ significantly (P=0.13) and were strongly correlated (r>0.70, P<0.05). There were no differences between boys and girls (P=0.43) and there was no significant correlation with VO2peak (P>0.05). It was shown that cerebral and muscle oxygenation responses undergo significant changes as work rate increases and show breakpoints in the ongoing response at high intensity (85-95%VO2peak). These breakpoints are strongly interrelated and associated with changes in pulmonary gas exchange.

The effects of oxygen induced pulmonary vasoconstriction on bedside measurement of pulmonary gas exchange.

In patients with respiratory failure measurements of pulmonary gas exchange are of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary gas exchange is based on changes in inspired oxygen (FiO2) assuming that these changes do not affect pulmonary circulation. This assumption is investigated in this study. Forty-two out of 65 patients undergoing coronary artery bypass grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP), cardiac output and pulmonary capillary wedge pressure thus enabling the calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20 and ultimately returned towards baseline values, allowing 6-8 min' steady state period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2 reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of 4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately reversed on returning FiO2 towards baseline. In this study changes in MPAP and PVR are small and immediately reversible consistent with small changes in pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary vasoconstriction does not have significant influences on the ALPE parameters in patients after CABG.

Changes in pulmonary gas exchange during resistive loading that do not cause a sense of shortness of breath

It is known that hypoxic hypometabolism occurs as a result of reduced delivery of oxygen to tissues. We have shown earlier that this response may be observed during latent hypoxia, when blood oxygen saturation (SpO2) is reduced to 95%. There is a hypothesis that the body can prevent a disturbance of the balance between oxygen delivery and consumption by developing a protective response to reduce oxygen demand. To test the hypothesis, a study was carried out under normal oxygenation conditions, in which a weak additional resistance of 0.4 cm H2O L−1 s was used as a trigger. The study sample comprised 14 healthy subjects of both sexes. Gas exchange parameters under normal and combined resistive loading conditions were studied. It was found that the respiratory rate was reduced by 8%, and the tidal volume was increased by 12%. At the same time, oxygen consumption and carbon dioxide production were significantly decreased by 9 and 10%, respectively. These findings suggest that a decrease in the rates of oxygen consumption and carbon dioxide production is a nonspecific protective response to prevent the disturbance of the balance between oxygen delivery and consumption.

LUNG AND LIVER CHANGES DUE TO THE INDUCTION OF CIRRHOSIS IN TWO EXPERIMENTAL MODELS

To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl4) and bile duct ligation (BDL). methods: Twenty-four male Wistar rats were divided into a control group (CO) and an experimental group (EX). We evaluated the liver transaminases (AST, ALT, AP), arterial blood gases (PaO2, PCO2 and SpO2) and lipid peroxidation by TBARS (substances that react to thiobarbituric acid) and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD) and histology of lung tissue and liver. There were significant differences in AST, ALT, ALP and PaO2 between CO group and EX group (P<0.05). The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05, respectively). In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange.

3 Level Ventilation: the First Clinical Experience

Considering the issues of artificial ventilation (AV) in non-homogenous pathological lung processes (acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pneumonia, etc.), the authors applied the three-level lung ventilation to a group of 12 patients with non-homogenous lung injury. Three-level ventilation was defined as a type (modification) of AV whose basic ventilation level was produced by the modes CMV, PCV or PS (ASB) and add-on level, the so-called background ventilation was generated by two levels of PEEP. PEEP (constant) and PEEPh (PEEP high) with varying frequency and duration of transition between the individual levels of PEEP. Objective: to elucidate whether in cases of considerably non-homogenous gas distribution in acute pathological disorders, three-level ventilation (3LV) can correct gas distribution into the so-called slow bronchoalveolar compartments, by decreasing the volume load of the so-called fast compartments and to improve lung gas exchange, by following the principles of safe ventilation. Results. 3LV was applied to 12 patients with severe non-homogenous lung injury/disorder (atypic pneumonia and ARDS/ALI) and low-success PCV ventilation after recruitment manoeuvre (PaO2 (kPA) /FiO2 = 5—6). There were pronounced positive changes in pulmonary gas exchange within 1—4 hours after initiation of 3LV at a fPCV of 26±4 breaths/min-1 and PEEPh at a fPEEPH of 7±2 breaths/min-1 with a minute ventilation of 12±4 l/min. 3LV reduced a intrapulmonary shunt fraction 50±5 to 30±5%, increased CO2 elimination, with PaCO2 falling to the values below 6±0.3 kPa, and PaO2 to 7.5±1.2 kPa, with FiO2 being decreased to 0.8—0.4. Lung recruitment also improved gas exchange: with PEEP=1.2±0.4 kPa, static tho-racopulmonary compliance (Cst) elevated from 0.18±0.02 l/kPa to 0.3±0.02 l/kPa and then to 0.38±0.05 l/kPa. Airways resistance (Raw) decreased by more than 30%. Improved lung aeration was also estimated as a manifestation of gas distribution with a long time constant. After 5±1-day 3LV, the patients were switched to PS ventilation; after gradually reduction of ventilation maintenance, they were disconnected from a ventilator and transferred to a specialized unit. Conclusion. The small study group made it impossible to statistically assess outcomes; the clinical results are not at least contrary to the results of theoretical mathematic simulation of 3LV in mathematical and physical models. 3LV as compared with PCV applied within the first 2—4 hours of AV improved lung gas exchange. It can be a promising mode of ventilation for the lungs afflicted by a diffusive non-homogenous pathological process. Key words: artificial ventilation, three-level ventilation, acute lung injury, acute respiratory distress syndrome.

The Impact of Prostanoids on Pulmonary Gas Exchange During Abdominal Surgery with Mesenteric Traction

We investigated the effect of intravenous (iv) ibuprofen on prostanoid release and on pulmonary gas exchange after abdominal mesenteric traction (MT) during either abdominal aortic surgery or pancreas resection.In a prospective, randomized, double-blind study, 400 mg ibuprofen (pancreas n = 13, aorta n = 13) or a placebo (pancreas n = 13, aorta n = 13) was administered iv before skin incision. MT was applied uniformly. The prostanoid plasma concentrations, venous admixture (Qva/Qt), and PaO (2/FIO)2 ratio were determined at baseline (before MT) and 5, 15, 45, and 90 min after MT. Patients who underwent aortic surgery were older and exhibited a lower preoperative PaO2 than those who underwent pancreas resection. Placebo-treated patients revealed a 30-fold peak increase in 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) levels after intentional MT during aortic as well as pancreatic operations. This response was accompanied by an increase in Qva/Q (t) (ibuprofen: pancreas 7% +/- 1%, aorta 14% +/- 2%; placebo: pancreas 16% +/- 3%, aorta 26% +/- 3%/15 min after MT [mean +/- SEM, p < 0.05, placebo vs ibuprofen]), which resulted in decreased PaO2/FIO2 ratio only in the aortic surgery patients (ibuprofen: 310 +/- 19; placebo: 237 +/- 24 15 min after MT, [mean +/- SEM, P < 0.05]). The authors conclude that ibuprofenpretreated patients demonstrated almost constant prostanoid levels without changes in pulmonary gas exchange after MT. (Anesth Analg 1997;85:274-80)

A porcine model of early adult respiratory distress syndrome induced by endotoxaemia.

To study the pathophysiology of early adult respiratory distress syndrome (ARDS) induced by sepsis, spontaneously breathing pigs under ketamine anaesthesia were investigated. Twenty animals were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h, and ten control animals received physiological saline. In the controls, cardiac output (Qt) and O2 delivery decreased slightly. There were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water (EVLW). The polymorphonuclear (PMN) leucocyte count gradually increased, while the platelet count decreased slightly. Endotoxin infusion caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in EVLW. The pulmonary dysfunction was not attributable to the pulmonary oedema per se, whereas a "dry" ventilation/perfusion inequality played an important role. The "responders" (peak venous admixture greater than 20%; n = 14) were characterized by higher Qt and lower PVR than the "non-responders". Qt declined progressively, especially in non-survivors. O2 delivery decreased considerably. Metabolic acidosis probably indicated oxygen deficit. Eleven of 20 animals died during the observation period. Mortality was related more to the imbalance between O2 delivery and oxygen demand than to the deterioration in pulmonary gas exchange. The PMN count decreased markedly while the gradual decline in platelet count was similar to that in the controls. Lung microscopy revealed PMN accumulation in the microvasculature, moderate interstitial oedema and microvascular blood stasis. Our porcine model, which closely mimics early ARDS in man, will be useful in further studies of the pathophysiological pathways and the treatment of this syndrome.

Impairment of pulmonary gas exchange during exercise in chronic pulmonary emphysema

Most data dealing with the pulmonary gas exchange in chronic pulmonary emphysema have been collected on resting subjects. The purpose of this study is to clarify the causes of the fall in arterial oxygen pressure which often occurs in exercising patients with chronic pulmonary emphysema. Materials and Methods In 10 patients with severe chronic pulmonary emphysema (FEV1 /VC averaged 30%) the determinations were performed during cardiac catheterization. These subjects exercised on the bicycle ergometer with a cardiac catheter placed in the main pulmonary artery, and an indwelling arterial needle in the brachial artery. Samples of arterial blood, mixed venous blood, and expired air were collected at rest and during exercise. These measurernents were followed by nitrogen washout studies. Estimates of the distribution of the pulmonary blood flow, ventilation and the ventilation-perfusion ratio were made by the modified Briscoe's methods. Results A) Changes of blood gas The arterial oxygen pressure (Pao2) and saturation (Sao2) at rest averaged 71±6.2 mmHg and 91.9±1.6% and fell during exercise to the average value of 59±7.3 mmHg and 86.9±3.1 % respectively. Mixed venous oxygen saturation (SVo2) at rest averaged 66.7±2.8% and fell during exercise to the average value of 40.1±7.8 %. B) Oxygen uptake Oxygen uptake (Vo2) increased remarkably from 263±45.3 ml/min to 748±214.0 ml/min during exercise. C) Alveolar ventilation and turn over rate Total alveolar ventilation (VAT) increased remarkably from 4.8±0.8 L/min at rest to 16.7±3.9 L/min during exercise, and the turn over rate in fast (VA1/L1) normal (VA2/L2 ), slow-ventilated space (VA3/L3) averaged 10.38±3.91, 1.57±0.49, 0.24±0.11, respectively at rest and increased to the average value of 11.82±3.20, 2.19±0.85, 0.36±0.10 during exercise. D) Cardiac output Cardiac output increased slightly from 5.3±1, 0 L/min to 8.0±1.3 L/min during exercise. E) Ventilation-perfusion ratio Ventilation-perfusion ratio in well (fast-normal)-ventilated space (VA1, 2/Q1, 2) and slow-ventilated space (VA3/Q3) averaged 1.44±0.33 and 0.26±0.06 at rest and increased to the average value of 3.78±0.41 and 0.47±0.13 respectively during exercise. F) Changes in slow-ventilated space with particular reference to end-capillary oxygen saturation Volume fraction of slow ventilated space (L3/LT) was 68±9.6% at rest and decreased to 61±11.3% during exercise. Estimated fraction of cardiac output perfusing slow-ventilated space (L3/lT) was 44±10% and slightly increased to 48 i 1 7% during exercise, and the perfusion index (Q3/QT/L3/LT) raised from 0.64±0.17 to 0.78±0.16. The calculated end-capillary oxygen saturation of slow-ventilated space (Sc3) was 84.2±2.4% at rest and fell to 74.7±4.6% during exercise. Discussion and Conclusions In the lower range of the ventilation-perfusion ratio as seen in the patients with chronic pulmonary emphysema, the fall of mixed venous oxygen saturation appeared to account for the fall in end-capillary, and arterial oxygen saturation. Thus, arterial oxygen pressure in the patiens with emphysema was very sensitive not only to the uneven ventilation-perfusion ratio but also to changes in oxygen consumption, and cardiac output. These findings serve to emphasize that studies of the uneveness of ventilation-perfusion ratio alone are not sufficient to interpret changes in pulmonary gas exchange in emphysema especially during exercise.