Alveolar-arterial PO2 Difference Research Articles

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for [formula omitted] Mismatch

The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vsNTG: 4.03 ± 2.18; P= .009) despite a clear decrease in pulmonary capillary wedge pressure at 20W (PLC: 19.7 ± 8.2 vsNTG: 15.9 ± 7.4mmHg; P< .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vsNTG: 0.31 ± 0.08 L/breath; P= .01), A-aDO2 (PLC: 19.6 ± 6.7 vsNTG: 21.1 ± 6.7; P= .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vsNTG: 40.2 ± 6.5; P< .001) all increased at 20W after a decrease in pulmonary capillary wedge pressure. These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

Abstract 12146: Acute Nitroglycerin Treatment Improves Exercise Hemodynamics, but Not Ventilation-Perfusion Matching in Patients With Heart Failure With Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) patients exhibit a marked rise in PCWP during exercise, which may contribute to ventilation-perfusion (V/Q) mismatch and manifest as an increase in alveolar dead space (alveolar V D ) and alveolar-arterial PO 2 difference (AaPO 2 ). Nitrates reduce PCWP during exercise in HFpEF, but whether nitrates also reduce V/Q mismatch during exercise is unknown. Hypothesis: The increase in PCWP and V/Q mismatch during exercise would be attenuated with acute nitroglycerin (NTG) treatment compared with placebo in HFpEF patients. Methods: 13 patients performed a 6min cycling test at 20W and an incremental cycling test (with right-heart and arterial catheterization) with placebo and NTG treatment. The physiologic dead space to tidal volume (V D /V T ) was calculated using the Enghoff modification of the Bohr equation. Alveolar V D was calculated as: V D /V T x V T - anatomic dead space (anatomic V D , estimated as 2mL/kg lean body mass). AaPO 2 was calculated using the alveolar gas equation. Data were analyzed using a 2-way ANOVA. Results: PCWP decreased with NTG at 20W (placebo: 21.1±6.2 vs. NTG: 16.5±6.1mmHg, p=0.02) and peak exercise (placebo: 33.7±7.1 vs. NTG: 26.2±5.6mmHg, p&lt;0.01). However, alveolar V D did not differ between treatments at rest (placebo: 0.11±0.07 vs. NTG:0.12±0.06L/breath, p=0.91), 20W (placebo: 0.22±0.09 vs. NTG: 0.24±0.10L/breath, p=0.62), or peak exercise (placebo: 0.34±0.14 vs. NTG:0.36±0.16L/breath, p=0.83). Nor did AaPO 2 differ between treatments at rest (placebo: 17.6±4.3 vs. NTG: 18.3±5.7mmHg, p=0.76), 20W (placebo: 22.0±6.9 vs. NTG: 22.1±8.1mmHg, p=0.99), or peak exercise (placebo: 25.1±9.1 vs. NTG: 27.8±9.9mmHg, p=0.41). No significant exercise-by-treatment interaction was detected for V D /V T (p=0.80). Conclusions: This study showed that NTG attenuated the increase in PCWP, but had no effect on the increase in alveolar V D or AaPO 2 during exercise. These findings suggest that the exercise-induced increase in V/Q mismatch may not be exclusively related to abnormal exercise hemodynamics. Further study is required to determine the clinical consequences and the mechanism(s) responsible for the progressive increase in V/Q mismatch during exercise in HFpEF patients.

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: comparing the "ideal" Po2 of Riley with end-tidal Po2.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

Oxygen deficit is a sensitive measure of mild gas exchange impairment at inspired O2 between 12.5% and 21.

The oxygen deficit (OD) is the difference between the end-tidal alveolar Po2 and the calculated Po2 of arterial blood based on measured oxygen saturation that acts as a proxy for the alveolar-arterial Po2 difference. Previous work has shown that the alveolar gas meter (AGM100) can measure pulmonary gas exchange, via the OD, in patients with a history of lung disease and in normal subjects breathing 12.5% O2. The present study measured how the OD varied at different values of inspired O2. Healthy subjects were split by age (young 22-31; n = 23; older 42-90; n = 13). Across all inspired O2 levels (12.5, 15, 17.5, and 21%), the OD was higher in the older cohort 10.6 ± 1.0 mmHg compared with the young -0.4 ± 0.6 mmHg (P < 0.0001, using repeated measures ANOVA), the difference being significant at all O2 levels (all P < 0.0001). The OD difference between age groups and its variance was greater at higher O2 values (age × O2 interaction; P = 0.002). The decrease in OD with lower values of inspired O2 in both cohorts is consistent with the increased accuracy of the calculated arterial Po2 based on the O2-Hb dissociation curve and with the expected decrease in the alveolar-arterial Po2 difference due to a lower arterial saturation. The persisting higher OD seen in older subjects, irrespective of the inspired O2, shows that the measurement of OD remains sensitive to mild gas exchange impairment, even when breathing 21% O2.

Deriving the arterial Po2 and oxygen deficit from expired gas and pulse oximetry.

The efficiency of pulmonary gas exchange is often assessed by the ideal alveolar-arterial partial pressure difference (A-aDO2). Through a combination of pulse oximetry and rapidly responding gas analyzers to measure the partial pressures of O2 and CO2 in expired gas, one can measure the oxygen deficit. Defined as the difference between the measured alveolar Po2 and the arterial Po2 calculated from , the oxygen deficit is a substitute for the alveolar-arterial Po2 difference. The oxygen deficit is physiologically reasonable in that it increases with age in healthy subjects and is well correlated with the A-aDO2. To calculate arterial Po2 from saturation, the saturation should be below the very flat upper part of the O2-Hb dissociation curve; good estimates can be made provided the arterial O2 saturation is below ~95%. Since saturations at or above 95% imply reasonably well-maintained gas exchange efficiency, this limitation is of only minor concern. Calculations show that it is necessary to take into account the change in Po2 at a saturation of 50% of the O2-Hb dissociation curve based on the measured alveolar Pco2. As the measurement is designed to be noninvasive, determination of any base excess is not practical, but calculations show that the effect of assuming a zero base excess is modest, with a similar small effect from an abnormal body temperature. Taken together, these results show that a noninvasive assessment of pulmonary gas exchange efficiency can be obtained from subjects with below-normal arterial O2 saturations through a combination of expired O2 and CO2 measurements and made during quiet breathing.NEW & NOTEWORTHY The details and limitations of a noninvasive measurement of pulmonary gas exchange efficiency, the oxygen deficit, are described. The oxygen deficit, calculated from expired gas measurements made during quiet breathing coupled with pulse oximetry, is a good surrogate measurement of the ideal alveolar-arterial Po2 difference and does not require arterial blood gas sampling.

Anatomical backgrounds on gas exchange parameters in the lung

Many problems regarding structure-function relationships have remained unsolved in the field of respiratory physiology. In the present review, we highlighted these uncertain issues from a variety of anatomical and physiological viewpoints. Model A of Weibel in which dichotomously branching airways are incorporated should be used for analyzing gas mixing in conducting and acinar airways. Acinus of Loeschcke is taken as an anatomical gas-exchange unit. Although it is difficult to define functional gas-exchange unit in a way entirely consistent with anatomical structures, acinus of Aschoff may serve as a functional gas-exchange unit in a first approximation. Based on anatomical and physiological perspectives, the multiple inert-gas elimination technique is thought to be highly effective for predicting ventilation-perfusion heterogeneity between acini of Aschoff under steady-state condition. Changes in effective alveolar PO2, the most important parameter in classical gas-exchange theory, are coherent with those in mixed alveolar PO2 decided from the multiple inert-gas elimination technique. Therefore, effective alveolar-arterial PO2 difference is considered useful for assessing gas-exchange abnormalities in lung periphery. However, one should be aware that although alveolar-arterial PO2 difference sensitively detects moderately low ventilation-perfusion regions causing hypoxemia, it is insensitive to abnormal gas exchange evoked by very low and high ventilation-perfusion regions. Pulmonary diffusing capacity for CO (DLCO) and the value corrected for alveolar volume (VAV), i.e. DLCO/VAV (KCO), are thought to be crucial for diagnosing alveolar-wall damages. DLCO-related parameters have higher sensitivity to detecting abnormalities in pulmonary microcirculation than those in the alveolocapillary membrane. We would like to recommend four categories derived from combining behaviors of DLCO with those of KCO for differential diagnosis on anatomically morbid states in alveolar walls: type-1 abnormality defined by decrease in both DLCO and KCO; type-2 abnormality by decrease in DLCO but increase in KCO; type-3 abnormality by decrease in DLCO but restricted rise in KCO; and type-4 abnormality by increase in both DLCO and KCO.

A clinical study of lung function protection in patients with robot assisted laparoscopic radical prostatectomy

Objective To evaluate the effect of manipulative pulmonary protective strategy on the pulmonary function of the patients undergoing robotic assisted laparoscopic radical prostatectomy under multiple-mode monitoring. Methods One hundred and twenty patients who underwent robot-assisted laparoscopic radical prostatectomy were divided into 4 groups (30 cases in each group) according to ASA Ⅰ-Ⅲ. Multimodal monitoring + manual relaxation group (group Mm), multimodal monitoring group (group M), conventional anesthesia + manual relaxation group (group m) and conventional anesthesia group (group C). In group Mm and group M, propofol was infused to achieve the BIS value of 45-55, then we monitored the muscle relaxation to conduct closed-loop infusion of cisatracurium. We also monitored and managed liquid input by vigileo. Group M and group C maintained peak airway pressure (≤30 cmH2O) (1 cmH2O=0.098 kPa) and PETCO2 35-40 mmHg (1 mmHg=0.133 kPa). Group Mm and group m received manual lung recruitment maneuver one times every 30 min after establishment of pneumoperitoneum until the end of operation. Blood gas analysis was performed before anesthesia induction (T1), 15 min after intubation (T2), 10 min after pneumoperitoneum (T3), 30 min after pneumoperitoneum (T4), 60 min after Trendelenburg (T5), 10 min after pneumoperitoneum cessation (T6), 5 min after extubation (T7). Airway peak pressure (Ppeak) and airway plateau pressure (Pplat) were recorded. The value of dynamic lung compliance (Cdyn), spiro-index (RI), dying cavity rate (VD/VT), oxygenation index (PaO2/FiO2) and alveolar arterial PO2 difference (A-aDO2) were calculated at different time points. Results Ppeak of group Mm and group m were more stable than Ppeak of group M and group C at T3 and T4 (P<0.05). Pplat of group Mm and group m were more stable than Pplat of group M and group C at T3 and T5 (P<0.05). Oxygenation indexes of group Mm and group m were higher than indexes of group M and group C at T5-T7 (P<0.05). A-aDO2 and RI were lower than group M and group C at T4, T5, T7 (P<0.05). At T4-T6, Cdyn was higher than Cdyn in group M and group C (P<0.05). Conclusions Manipulative pulmonary protective ventilation can improve the pulmonary function in patients undergoing robotic assisted laparoscopic radical prostatectomy under multimode monitoring. Key words: Robot; Therapeutic laparoscopy; Protective lung ventilation; Multi-mode monitoring; Prostate cancer

Short-term outcomes of minimally invasive mitral valve repair: a propensity-matched comparison.

We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary function and haemodynamics, as well as its short-term efficacy. From March 2012 to July 2015, 78 cases of minimally invasive mitral valve repair and 89 cases of conventional mitral valve repair were included in this study, with 67 well-matched pairs of patients identified by a propensity score matching, who were divided into the conventional sternotomy group and the right minithoracotomy group (the RT group). The in-hospital mortality was similar between the 2 groups (3.0% vs 1.5%, P = 1.000). Both cross-clamp time and bypass time were higher in the RT group (P < 0.001), whereas drainage amount, blood transfusion and length of intensive care unit stay were higher in the conventional sternotomy group (P < 0.001). There was not much discrepancy in pulmonary function between the 2 groups, except that partial pressure of O2 in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) in the RT group was significantly lower than that in the conventional sternotomy group 0, 4 and 8 h after surgery (P < 0.05), whereas the extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI) and alveolar-arterial PO2 difference (PA-aO2) of the RT group was higher (P < 0.05). We found no disparity in haemodynamics (P > 0.05), incidence of complications (P > 0.05) and short-term recurrence between the 2 groups (P = 0.7697). When compared with the median sternotomy approach, the RT approach shows comparable results in short-term efficacy and safety. On relatively increasing cardiopulmonary bypass time and operation time, the RT approach shortens the patient's intensive care unit stay and reduces the need for blood transfusion. Pulmonary function may be affected shortly post-surgery in the RT approach, with insignificant difference in haemodynamics.

A new method for noninvasive measurement of pulmonary gas exchange using expired gas

Measurement of the gas exchange efficiency of the lung is often required in the practice of pulmonary medicine and in other settings. The traditional standard is the values of the PO2, PCO2, and pH of arterial blood. However arterial puncture requires technical expertise, is invasive, uncomfortable for the patient, and expensive. Here we describe how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency. The new procedure is noninvasive, well tolerated by the patient, and takes only a few minutes. It could be particularly useful when repeated measurements of pulmonary gas exchange are required. One product of the procedure is the difference between the PO2 of end-tidal alveolar gas and the calculated PO2 of arterial blood. This measurement is related to the classical alveolar-arterial PO2 difference based on ideal alveolar gas. However that traditional index is heavily influenced by lung units with low ventilation-perfusion ratios, whereas the new index has a broader physiological basis because it includes contributions from the whole lung.

Predictors of high flow nasal cannula failure in immunocompromised patients with acute respiratory failure due to non-HIV pneumocystis pneumonia.

To evaluate the predictors of high flow nasal cannula (HFNC) failure in pneumocystis pneumonia (PCP) patients with acute respiratory failure (ARF). Fifty-two non-HIV-related PCP subjects were divided into a HFNC success group (44%) and a HFNC failure group (who required mechanical ventilation (MV) despite HFNC application) (56%). The clinical characteristics and physiologic effects were retrospectively reviewed and compared between the groups. At baseline, the heart rate, alveolar-arterial PO2 difference [P(A-a)O2], Sequential Organ Failure Assessment (SOFA) score, and proportion of subjects who used vasopressors were significantly higher in the HFNC failure group than in the HFNC success group. The 60-day mortality was 52% in the HFNC failure group and 13% in the HFNC success group (P=0.004). The results of the multivariate analysis indicated that the baseline SOFA score was independently associated with HFNC failure (adjusted odds ratio, 1.74 per each score unit increase; 95% CI, 1.05-2.89; P=0.03). Repeated measures analysis of variance revealed that within 6 h of HFNC initiation, the mean PaO2/FiO2 ratio decreased and the mean P(A-a)O2 increased rapidly in the HFNC failure group. Patients with ARF due to PCP subjected to HFNC therapy should be carefully monitored, and particular attention should be paid to those who had organ dysfunction and did not show early oxygenation improvement.

Increased blood-oxygen binding affinity in Tibetan and Han Chinese residents at 4200 m.

High-altitude natives are challenged by hypoxia, and a potential compensatory mechanism could be reduced blood oxygen-binding affinity (P50), as seen in several high-altitude mammalian species. In 21 Qinghai Tibetan and nine Han Chinese men, all resident at 4200m, standard P50 was calculated from measurements of arterial PO2 and forehead oximeter oxygen saturation, which was validated in a separate examination of 13 healthy subjects residing at sea level. In both Tibetans and Han Chinese, standard P50 was 24.5±1.4 and 24.5±2.0mmHg, respectively, and was lower than in the sea-level subjects (26.2±0.6mmHg, P<0.01). There was no relationship between P50 and haemoglobin concentration (the latter ranging from 15.2 to 22.9gdl(-1) in Tibetans). During peak exercise, P50 was not associated with alveolar-arterial PO2 difference or peak O2 uptake per kilogram. There appears to be no apparent benefit of a lower P50 in this adult high-altitude Tibetan population.

Rebuttal to Pro Statements

High-altitude (HA) natives show distinctive physical and functional characteristics that give them an advantage over lowlanders at HA. These advantages are not confined to the cardio-respiratory or hematological systems, as they include indeed the whole organism, and must be reflected in different regions of the brain. In this regard, the reduced cerebrovascular reactivity in HA natives reported by Yan et al., (2011a) was particularly manifested among brain regions involved in cerebral modulation of respiration. Hochachka and co-workers have shown that lower regionby-region brain glucose metabolic rates in HA Quechuas compared to lowlanders may be the result of a defense adaptation against chronic hypoxia (Hochachka et al., 1994). Also, the psychomotor slowing observed in European, Native American, and African altitude groups is proposed to be an adaptive rather than a deficient trait (Hogan et al., 2010). In addition, the very scarce studies in spatial working memory matched by age, gender ratio, educational level, and ancestral lines, show equal accuracy response in HA compared to SL groups, but with more variability in reaction time; and the same activation patterns in their neural pathways (Yan et al., 2011b). Evaluation of the effects of altitude on mood, behavior profile, and cognitive function is complicated by differences between studies, including the specific methods of measurement and type of participants, which explain why there are so few. Since most of the systematic research in these areas has been conducted in exposure to experimental acute or moderate-lasting hypoxia, the results should not be generalized to altitude settings. On the physical side, besides being able to run a complete marathon at 4300 m, superior pulmonary gas-exchange and acidbase state in HA natives was evidenced by Wagner et al. (2002) and Lundby et al. (2004), who compared lowlanders acclimatized to 5260 m with HA natives at the same altitude in Bolivia. During exercise, HA natives showed smaller alveolar-arterial Po2 difference, 40% higher O2-diffusing capacity, and greater lactic acid buffering. In addition, despite lower anaerobic capacities, HA natives were capable of calf muscle work rates equal to those of highly-trained power athletes (Matheson et al., 1991). Also, aerobic exercise capacity of chronic mountain sickness patients with significant erythrocytosis is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of blood and pulmonary O2-diffusion (Groepenhoff et al., 2012). Even though in his later publication (Barcroft, 1925), concluded that acclimatization to HA does not exist, generalizing this concept even to HA natives, Barcroft was very impressed by the physical capacities of the Peruvian Andean natives, and this was certainly an accurate feeling.

Effects of hyperoxia on ventilation and pulmonary hemodynamics during immersed prone exercise at 4.7 ATA: possible implications for immersion pulmonary edema

Immersion pulmonary edema (IPE) can occur in otherwise healthy swimmers and divers, likely because of stress failure of pulmonary capillaries secondary to increased pulmonary vascular pressures. Prior studies have revealed progressive increase in ventilation [minute ventilation (Ve)] during prolonged immersed exercise. We hypothesized that this increase occurs because of development of metabolic acidosis with concomitant rise in mean pulmonary artery pressure (MPAP) and that hyperoxia attenuates this increase. Ten subjects were studied at rest and during 16 min of exercise submersed at 1 atm absolute (ATA) breathing air and at 4.7 ATA in normoxia and hyperoxia [inspired P(O(2)) (Pi(O(2))) 1.75 ATA]. Ve increased from early (E, 6th minute) to late (L, 16th minute) exercise at 1 ATA (64.1 +/- 8.6 to 71.7 +/- 10.9 l/min BTPS; P < 0.001), with no change in arterial pH or Pco(2). MPAP decreased from E to L at 1 ATA (26.7 +/- 5.8 to 22.7 +/- 5.2 mmHg; P = 0.003). Ve and MPAP did not change from E to L at 4.7 ATA. Hyperoxia reduced Ve (62.6 +/- 10.5 to 53.1 +/- 6.1 l/min BTPS; P < 0.0001) and MPAP (29.7 +/- 7.4 to 25.1 +/- 5.7 mmHg, P = 0.002). Variability in MPAP among subjects was wide (range 14.1-42.1 mmHg during surface and depth exercise). Alveolar-arterial Po(2) difference increased from E to L in normoxia, consistent with increased lung water. We conclude that increased Ve at 1 ATA is not due to acidosis and is more consistent with respiratory muscle fatigue and that progressive pulmonary vascular hypertension does not occur during prolonged immersed exercise. Wide variation in MPAP among healthy subjects is consistent with variable individual susceptibility to IPE.

Comments on Point:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. real

Comments on Point:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. real

The effects of nitric oxide inhalation on pulmonary surfactant during cardiopulmonary bypass in infants with severe CHD

Objective To study the effects of inhale nitric oxide(NO) on pulmonary surfactant during cardiopulmonary bypass(CPB) in infants with severe CHD. Methods Thirty infants with severe CHD were randomly divided into two groups:control group(n=15) and NO group(n=15). Before CPB and after operation 0～1 h, 1～2 h,2～3 h, the cases of NO group had been inhaled 40×10-6 NO till the operation finished. We monitored the followings:mean pulmonary arterial pressure, fractional concentration of inspired oxygen ,end-tidal CO2, the value of volume of dead air space/ tidal volume (VD/VT ), oxygen index (OI), alveolar-arterial PO2 difference[ P(A-a)O2] and oxygen content in arterial blood( CaO2 ). Meanwhile branchoalveolar lavage fluid in each phase point were collected to analyse,the levels of TPL,SatPC,TP were determined and the value of SatPC/TPL and SatPC/TP were calculated. Results The VD/VT P(A-a) O2 in control group were much higher than those in NO group, OI and CaO2 in NO group were higher than those in control group(P<0.01 ). The levels of SatPC/TPL and SatPC/TP at post-operation were lower than those before CPB (P<0.01), and the decreases of SatPC/TPL and SatPC/TP in control group were more than those in NO group. Conclusion Lung ischemia-reperfusion injury was observed obviously during CPB in infants with severe CHD, which manifestes subclinical pulmonary function injury. Inhaled NO has protective effects on lung during CPB in infants with severe CHD. Key words: Cardiopulmonary bypass; Congenital heart disease; Pulmonary surfactant; Nitric oxide

Air to Muscle O2Delivery during Exercise at Altitude

Hypoxia-induced hyperventilation is critical to improve blood oxygenation, particularly when the arterial Po2 lies in the steep region of the O2 dissociation curve of the hemoglobin (ODC). Hyperventilation increases alveolar Po2 and, by increasing pH, left shifts the ODC, increasing arterial saturation (Sao2) 6 to 12 percentage units. Pulmonary gas exchange (PGE) is efficient at rest and, hence, the alveolar-arterial Po2 difference (Pao2-Pao2) remains close to 0 to 5mm Hg. The (Pao2-Pao2) increases with exercise duration and intensity and the level of hypoxia. During exercise in hypoxia, diffusion limitation explains most of the additional Pao2-Pao2. With altitude, acclimatization exercise (Pao2-Pao2) is reduced, but does not reach the low values observed in high altitude natives, who possess an exceptionally high DLo2. Convective O2 transport depends on arterial O2 content (Cao2), cardiac output (Q), and muscle blood flow (LBF). During whole-body exercise in severe acute hypoxia and in chronic hypoxia, peak Q and LBF are blunted, contributing to the limitation of maximal oxygen uptake (Vo2max). During small-muscle exercise in hypoxia, PGE is less perturbed, Cao2 is higher, and peak Q and LBF achieve values similar to normoxia. Although the Po2 gradient driving O2 diffusion into the muscles is reduced in hypoxia, similar levels of muscle O2 diffusion are observed during small-mass exercise in chronic hypoxia and in normoxia, indicating that humans have a functional reserve in muscle O2 diffusing capacity, which is likely utilized during exercise in hypoxia. In summary, hypoxia reduces Vo2max because it limits O2 diffusion in the lung.

Point:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. real

Pulmonary gas exchange efficiency deteriorates with exercise in both humans and other species, increasing the alveolar-arterial PO2 difference (AaDO2) ([2][1]). The potential contributors to this are ventilation-perfusion inequality, alveolar-capillary diffusion limitation, and shunt ([20][2]).

The contribution of intrapulmonary shunts to the alveolar‐to‐arterial oxygen difference during exercise is very small

Exercise is well known to cause arterial PO2 to fall and the alveolar-arterial PO2 difference(Aa PO2 ) to increase. Until recently, the physiological basis for this was considered to be mostly ventilation/perfusion ((.)VA/(.)Q) inequality and alveolar-capillary diffusion limitation. Recently, arterio-venous shunting through dilated pulmonary blood vessels has been proposed to explain a significant part of the Aa PO2 during exercise. To test this hypothesis we determined venous admixture during 5 min of near-maximal, constant-load, exercise in hypoxia (in inspired O2 fraction, FIO2 , 0.13), normoxia (FIO2 , 0.21) and hyperoxia (FIO2 , 1.0) undertaken in balanced order on the same day in seven fit cyclists ((.)VO2max, 61.3 +/- 2.4 ml kg(-1) min(-1); mean +/- S.E.M.). Venous admixture reflects three causes of hypoxaemia combined: true shunt, diffusion limitation and ((.)VA/(.)Q) inequality. In hypoxia, venous admixture was 22.8 +/- 2.5% of the cardiac output; in normoxia it was 3.5 +/- 0.5%; in hyperoxia it was 0.5 +/- 0.2%. Since only true shunt accounts for venous admixture while breathing 100% O2, the present study suggests that shunt accounts for only a very small portion of the observed venous admixture, Aa PO2 and hypoxaemia during heavy exercise.

Pulmonary gas exchange does not worsen during repeat exercise in women

The purposes were to determine (1) if repeat exercise worsens pulmonary gas exchange in women, and, (2) if the level of pulmonary edema obtained in these same women is related to the gas exchange impairment during exercise. Fourteen women (27 +/- 4 yrs; maximal oxygen uptake = 3.12 +/- 0.42 L/min) with minimal arterial PO2 (PaO2) ranging from 76 to 104 mmHg with a maximal alveolar-arterial PO2 difference (AaDO2) ranging from 7 to 35 mmHg performed three bouts of near-maximal exercise on a cycle ergometer (236 +/- 27 W) for 5 min each with 10 min of rest between sets. Cardiorespiratory parameters and oxygenation were measured at rest, throughout exercise and recovery. Chest radiographs were obtained before and 30 min after the interval training session (see Respir Physiol Neurobiol, 153 (2006) 181-190). Repeat exercise did not affect pulmonary gas exchange between sets 1 and 3 (change in PaO2 = 3 +/- 2 mmHg; change in AaDO2 = 1 +/- 2 mmHg P > 0.05). Arterial PCO2 decreased by 4 +/- 2 mmHg (P < 0.05) between sets 1 and 2, which did not reduce further in set 3. The level of PaO2 or AaDO2 was not related to the change in edema score or the post-exercise edema score (P > 0.05). In conclusion, pulmonary gas exchange is not worsened in women during interval training despite the mild edema triggered by exercise.

Exercise training improves lung gas exchange and attenuates acute hypoxic pulmonary hypertension but does not prevent pulmonary hypertension of prolonged hypoxia

Our laboratory has previously shown an attenuation of hypoxic pulmonary hypertension by exercise training (ET) (Henderson KK, Clancy RL, and Gonzalez NC. J Appl Physiol 90: 2057-2062, 2001), although the mechanism was not determined. The present study examined the effect of ET on the pulmonary arterial pressure (Pap) response of rats to short- and long-term hypoxia. After 3 wk of treadmill training, male rats were divided into two groups: one (HT) was placed in hypobaric hypoxia (380 Torr); the second remained in normoxia (NT). Both groups continued to train in normoxia for 10 days, after which they were studied at rest and during hypoxic and normoxic exercise. Sedentary normoxic (NS) and hypoxic (HS) littermates were exposed to the same environments as their trained counterparts. Resting and exercise hypoxic arterial P(O2) were higher in NT and HT than in NS and HS, respectively, although alveolar ventilation of trained rats was not higher. Lower alveolar-arterial P(O2) difference and higher effective lung diffusing capacity for O2 in NT vs. NS and in HT vs. HS suggest ET improved efficacy of gas exchange. Pap and Pap/cardiac output were lower in NT than NS in hypoxia, indicating that ET attenuates the initial vasoconstriction of hypoxia. However, ET had no effect on chronic hypoxic pulmonary hypertension: Pap and Pap/cardiac output in hypoxia were similar in HS vs HT. However, right ventricular weight was lower in HT than in HS, although Pap was not different. Because ET attenuates the initial pulmonary vasoconstriction of hypoxia, development of pulmonary hypertension may be delayed in HT rats, and the time during which right ventricular afterload is elevated may be shorter in this group. ET effects may improve the response to acute hypoxia by increasing efficacy of gas exchange and lowering right ventricular work.