Estimating the effect of lung collapse and pulmonary shunt on gas exchange during breath-hold diving: the Scholander and Kooyman legacy

We developed a mathematical model to investigate the effect of lung compression and collapse (pulmonary shunt) on the uptake and removal of O(2), CO(2) and N(2) in blood and tissue of breath-hold diving mammals. We investigated the consequences of pressure (diving depth) and respiratory volume on pulmonary shunt and gas exchange as pressure compressed the alveoli. The model showed good agreement with previous studies of measured arterial O(2) tensions (Pa(O)(2)) from freely diving Weddell seals and measured arterial and venous N(2) tensions from captive elephant seals compressed in a hyperbaric chamber. Pulmonary compression resulted in a rapid spike in Pa(O)(2) and arterial CO(2) tension, followed by cyclical variation with a periodicity determined by Q(tot). The model showed that changes in diving lung volume are an efficient behavioural means to adjust the extent of gas exchange with depth. Differing models of lung compression and collapse depth caused major differences in blood and tissue N(2) estimates. Our integrated modelling approach contradicted predictions from simple models, and emphasised the complex nature of physiological interactions between circulation, lung compression and gas exchange. Overall, our work suggests the need for caution in interpretation of previous model results based on assumed collapse depths and all-or-nothing lung collapse models.     

肺脏的水孔蛋白家族

90年代以来 ,作为膜上水分子通道的水孔蛋白(ａｑｕａｐｏｒｉｎｓ ,ＡＱＰｓ)家族克隆成功[1,2 ] ,对自由水被动跨膜转运机制做出更加形象而深入的解释。肺脏的许多生理功能都有水分子运动的参与 ,同时许多肺脏疾病 ,如哮喘、肺水肿和急性呼吸窘迫综合征等也涉及肺内水运动平衡的紊乱。因此肺内水孔蛋白的分布及其病理生理意义日益受到重视。1　水孔蛋白的结构与功能特点水孔蛋白属于膜主体内在蛋白 (ｍａｊｏｒｉｎｔｅｒｎａｌｐｒｏｔｅｉｎ ,ＭＩＰ)家族的成员 ,目前在人类和哺乳动物身上共发现 10个亚型 ,广泛分布于多个组织器官 ,具…     

A pocket calculator program for noninvasive assessment of cardiorespiratory function

A pocket calculator program is described which facilitates rapid evaluation of pulmonary function at rest and during exercise. It embodies the Fick Principle applied to carbon dioxide; mixed venous carbon dioxide tension is measured by rebreathing, obviating the need for central venous or pulmonary artery catheterisation. The program is in two parts, Gas Phase and Blood Phase, which may be used separately. The variables calculated include tidal volume, CO2 production, oxygen consumption, respiratory quotient, alveolar ventilation and dead space: tidal volume ratio (Gas Phase); bicarbonate concentration, base excess, veno-arterial CO2 content difference, cardiac output, mixed venous oxygen saturation and pulmonary venous admixture (Blood Phase). Use of the program enables these variables to be calculated rapidly and accurately. Accuracy is improved by the application of equations which correct for alveolar-to-blood tension differences, effects of differing hemoglobin concentrations, arterial oxygen saturations and acid-base abnormalities; these calculations are otherwise very lengthy, time consuming and prone to error. The program allows simple noninvasive measurements to be applied to patients with a wide variety of metabolic, cardiac and pulmonary abnormalities in rest and exercise.     

Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

OBJECTIVE:Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease.METHODS:Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm) as well as values for the inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi) and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and the respiratory cycle dependence (ΔZrs=Ze-Zi) were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01888705","term_id":"NCT01888705"}}NCT01888705.RESULTS:Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p<0.0001). In contrast to the control subjects and the smokers, the chronic obstructive pulmonary disease patients presented significant expiratory-inspiratory differences (p<0.002). The adverse effects of moderate airway obstruction were detected based on the Zpp with an accuracy of 83%. Additionally, abnormal effects in severe and very severe patients were detected based on the Zm, Zi, Ze, Zbe, Zpp and ΔZrs with a high degree of accuracy (>90%).CONCLUSIONS:We conclude the following: (1) chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2) this increase is proportional to airway obstruction, and (3) the within-breath forced oscillation technique may provide novel parameters that facilitate the diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.     

Effect of tacrolimus on endotoxin-induced lung injury in sheep

Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.     

联合应用PS及机械通气治疗新生儿呼吸窘迫综合征

目的：探讨肺表面活性物质联合机械通气治疗新生儿呼吸窘迫综合征的疗效。方法：联合应用肺表面活性物质和机械通气治疗25例新生儿呼吸窘迫综合征患儿，对治疗前后临床表现、动脉血气、呼吸机参数、胸部X线变化等进行观察。结果：用药后患儿临床症状明显好转，胸部X线透亮度明显改善、颗粒网状阴影消失，血气分析及机械通气参数如FiO2、PIP、PEEP值明显降低（P〈0．01）。结论：肺表面活性物质联合机械通气能迅速有效地治疗新生儿呼吸窘迫综合征。     

Redox signaling in oxygen sensing by vessels

In response to the increase in oxygen tension at birth, the resistance pulmonary arteries dilate, while the ductus arteriosus constricts. Although modulated by the endothelium, these opposite responses are intrinsic to the vascular smooth muscle. While still controversial, it seems likely that during normoxia the production of reactive oxygen species (ROS) increases and the smooth muscle cell cytoplasm is more oxidized in both pulmonary arteries and ductus, compared to hypoxia. However, the effect of changes in the endogenous redox status or the addition of a redox agent, oxidizing or reducing, is exactly opposite in the two vessels. A reducing agent, dithiothreitol, like hypoxia, in the pulmonary artery will inhibit potassium current, cause depolarization, increase cytosolic calcium and lead to contraction. Responses to dithiothreitol in the ductus are opposite and removal of endogenous H(2)O(2) by intracellular catalase in the ductus increases potassium current. Oxygen sensing in both vessels is probably mediated by redox effects on both calcium influx and calcium release from the sarcoplasmic reticulum (SR).     

Effects of pulmonary gas embolism on circulation and respiration in the dog

Summary The purpose of this investigation was to find an explanation for the arterial hypoxemia which occurs during pulmonary gas embolism in normoxic conditions. Infusion of oxygen at a rate of 3.2 ml min^–1 during constant artificial ventilation led to an increase of the normoxic shunt percentage from 2.9 to 21.8. When excluding the contribution of lung units with low ventilation-perfusion ratios to the total shunt by breathing hyperoxic gas mixtures, the remaining hyperoxic shunt percentage increased from 2.9 to only 4.3 during inhalation of pure oxygen. There was a linear relationship between this hyperoxic shunt percentage and the degree of pulmonary gas embolization as expressed by the ratio of diastolic pulmonary arterial pressure with and without embolization. A comparison of the normoxic and hyperoxic increases of shunt percentage due to pulmonary gas embolism suggests that a major part of the arterial hypoxemia in normoxic condition is due to a marked increase in the number of lung units with low ventilation-perfusion ratios, i.e., by an enhanced unevenness of the distribution of the ventilation-perfusion ratio in the lungs. A moderate increase of the physiological dead space indicates some increase of lung units with high ventilation-perfusion ratios or of the alveolar dead space. The minor increase of the hyperoxic shunt percentage, expressing venous admixture by anatomical veno-arterial and possible atelectatic shunting, is probably due to atelectatic areas in the lungs. CO₂ elimination during the same extent of pulmonary gas embolization was more impaired during hyperoxia than during normoxia. This effect may be due to the release of hypoxic vasoconstriction in lung units with low ventilation-perfusion ratios during air breathing by hyperoxia, so that more blood would be shifted to these lung units. The elimination of CO₂ from that blood is impaired because the CO₂ pressure gradient is too small to compensate for the low ventilation in these lung units.     

Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease

We studied the effect of supplemental nocturnal oxygen on blood gases in 15 patients with severe but stable chronic obstructive lung disease (ratio of forced expired volume in one second to forced vital capacity, 37.2 +/- 1.8 [mean +/- S.E.] per cent of predicted; arterial oxygen tension, 50.7 +/- 1.4 mm Hg; and arterial carbon dioxide tension [PCO2], 53.1 +/- 1.5 mm Hg). Sleep variables and measures of gas exchange were determined on two consecutive nights; on the first night the subjects breathed supplemental oxygen, and on the second they breathed room air. Transcutaneous PCO2 was measured with an infrared sensor, and arterial oxygen saturation with an ear oximeter. Breathing of supplemental oxygen sufficient to keep oxygen saturation at or above 90 per cent was associated with only small increases (less than 6 mm Hg) in PCO2 throughout sleep, as compared with values while subjects were breathing room air. The increase in PCO2 occurred early in the night and was not progressive. Only three patients, who were found to have obstructive sleep apnea in addition to obstructive lung disease, had larger increases in PCO2 during sleep and reported morning headaches. We conclude that nocturnal oxygen does not induce clinically important increases in PCO2 during sleep in patients with stable obstructive lung disease and therefore can safely be used to prevent the dangerous consequences of hypoxia.     

Acute and chronic hypoxic pulmonary vasoconstriction: a central role for endothelin-1?

In the pulmonary circulation, a decrease in oxygen tension results in the development of hypoxic pulmonary vasoconstriction (HPV), although the exact mechanism by which HPV occurs remains unclear. Evidence gathered from many laboratories suggests that while pulmonary arterial smooth muscle cells (PASMCs) can sense and respond to changes in oxygen tension, full expression of HPV requires modulating influences from the endothelium. In this review, we propose a model of HPV, based on recent studies from our laboratory, in which endothelin-1 (ET-1), a vasoactive peptide released from the endothelium, plays a central role and discuss how this model may be involved in the long-term adaptation to hypoxia.     

Multicenter comparative study of conventional mechanical gas ventilation to tidal liquid ventilation in oleic acid injured sheep

We performed a multicenter study to test the hypothesis that tidal liquid ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p < 0.01) during TLV than CMV: PaO2, venous oxygen saturation, respiratory compliance, cardiac output, stroke volume, oxygen delivery, ventilatory efficiency index; alveolar area, lung % gas exchange space, and expansion index. The following were lower (p < 0.01) during TLV compared with CMV: inspiratory and expiratory pause pressures, mean airway pressure, minute ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.     

Single breath‐hold measurement of pulmonary gas exchange and diffusion in humans with hyperpolarized 129Xe MR

Pulmonary diseases usually result in changes of the blood‐gas exchange function in the early stages. Gas exchange across the respiratory membrane and gas diffusion in the alveoli can be quantified using hyperpolarized ¹²⁹Xe MR via chemical shift saturation recovery (CSSR) and diffusion‐weighted imaging (DWI), respectively. Generally, CSSR and DWI data have been collected in separate breaths in humans. Unfortunately, the lung inflation level cannot be the exactly same in different breaths, which causes fluctuations in blood‐gas exchange and pulmonary microstructure. Here we combine CSSR and DWI obtained with compressed sensing, to evaluate the gas diffusion and exchange function within a single breath‐hold in humans. A new parameter, namely the perfusion factor of the respiratory membrane (SVR_d/g), is proposed to evaluate the gas exchange function. Hyperpolarized ¹²⁹Xe MR data are compared with pulmonary function tests and computed tomography examinations in healthy young, age‐matched control, and chronic obstructive pulmonary disease human cohorts. SVR_d/g decreases as the ventilation impairment and emphysema index increase. Our results indicate that the proposed method has the potential to detect the extent of lung parenchyma destruction caused by age and pulmonary diseases, and it would be useful in the early diagnosis of pulmonary diseases in clinical practice.     

Anoxic ventilation improves systemic perfusion during extracorporeal circulation with uncontrolled systemic-to-pulmonary shunt

Uncontrolled systemic-to-pulmonary shunt results in decreased systemic flow during extracorporeal life support (ECLS). Ligation of systemic-to-pulmonary shunts during ECLS is associated with poor outcome and is not always readily achieved. In ex vivo preparations, alveolar hypoxia results in pulmonary vasoconstriction despite normoxic pulmonary perfusate. We hypothesized that anoxic ventilation would result in reduced pulmonary shunting and increased systemic flow during ECLS in piglets with systemic-to-pulmonary shunt. Four piglets were placed on ECLS with right and left atrial drainage. A shunt was created between the bicarotid trunk and pulmonary artery, using 5-mm ePTFE tubing. Inspired oxygen was reduced to <1% for 10 minutes, then returned to room air; pH, hematocrit, temperature, ventilatory pressures, and total pump flow were maintained constant. Systemic arterial pressure and right atrial return volume and hemoglobin saturation were measured: All decreased significantly upon shunt unclamping. Anoxic ventilation caused increased systemic pressure (34 vs. 28 mm Hg, p < 0.05), flow (335 vs. 278 mL/min, p < 0.05), and systemic venous saturation (53% vs. 48%, p = 0.13) compared with room air ventilation. In conclusion, anoxic ventilation during normoxic ECLS in subjects with systemic-to-pulmonary shunts results in a significant and potentially clinically useful reduction in pulmonary shunting.     

Outcome prediction in adult respiratory distress syndrome using discriminant analysis of cardiorespiratory data.

In order to examine the prognostic value of different cardiopulmonary variables in adult respiratory distress syndrome the data of 30 patients with this illness were studied retrospectively. The patients were divided into 3 groups: Group A: survivors (9 cases, 40 examinations), Group B: early stage nonsurvivors (8 cases, 37 examinations), Group C: late stage nonsurvivors (19 cases, 89 examinations). In 6 nonsurvivor patients a few measurements were done in the early and late stage, too. There were highly significant differences between Groups A and C (mean pulmonary arterial pressure, pulmonary arterial diastolic pressure minus pulmonary capillary wedge pressure, left ventricular stroke work index, systemic and pulmonary vascular resistance, inspired oxygen fraction, arterial oxygen tension per inspired oxygen fraction, mixed venous oxygen saturation, pulmonary shunt fraction, and oxygen delivery, but the differences in relation to other groups were less prominent. Using a step-wise discriminant analysis, it was found that the oxygenation parameters alone determined the outcome correctly in 68-75%. Extending the analysis to haemodynamic variables the result improved (72-80%). Similar prediction was obtained when parameters potentionally measurable by noninvasive methods were analysed (69-80%). These results suggest that it is possible to predict the outcome of ARDS correctly without any invasive monitoring technique.     

肾上腺髓质素对高肺血流大鼠肺组织氧化应激的调节作用

目的:研究肾上腺髓质素(ADM)对高肺血流性肺动脉高压大鼠肺组织氧化应激的调节作用及其机制。方法:健康雄性SD大鼠随机分为对照组、分流组和分流+ADM组。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+ADM组大鼠皮下埋微量渗透泵持续予ADM 1.5μg·kg~(-1)·h~(-1)。继续饲养2周后,右心导管法测定平均肺动脉压(mPAP)和右心室/(左心室+室间隔)重量比值,检测肺中、小肌型动脉相对中膜厚度(RMT),比色法测定肺组织匀浆丙二醛(MDA)含量、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性,Western blot法检测肺组织还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)的表达。结果:与对照组相比,分流组大鼠的mPAP、右心室肥厚程度以及肺中、小肌型动脉RMT均明显增加,肺组织MDA含量明显升高,T-AOC、SOD活性和GSH-Px活性均明显降低,肺组织NOX4表达明显升高。ADM使肺动脉压力明显回降,右心室肥厚程度减轻,肺血管结构改变缓解,肺组织MDA含量明显下降,T-AOC、SOD活性和GSH-Px活性明显升高,肺组织NOX4表达明显降低。结论:ADM能够抑制大鼠高肺血流性肺动脉高压和肺血管结构重构形成中的氧化应激反应,作用机制可能与其下调肺组织NOX4表达以及增强抗氧化活性有关。     

Total inspiratory and expiratory impedance in patients with severe chronic obstructive pulmonary disease

OBJECTIVES:

Several studies have confirmed the high potential of the forced oscillation technique for the assessment of respiratory modifications related to chronic obstructive pulmonary disease. However, most of these studies did not employ within-breath analyses of the respiratory system. The aim of this study is to analyze respiratory impedance alterations in different phases of the respiratory cycle of chronic obstructive pulmonary disease patients and to evaluate their clinical use.

METHODS:

39 individuals were evaluated, including 20 controls and 19 individuals with chronic obstructive pulmonary disease who experienced severe airway obstruction. We evaluated the mean respiratory impedance (Zm) as well as values for inspiration (Zi) and expiration cycles (Ze), at the beginning of inspiration (Zbi) and expiration (Zbe). The peak-to-peak impedance (Zpp), and the impedance change (ΔZrs) were also analyzed. The clinical usefulness was evaluated by investigating the sensibility, specificity and the area under the receiver operating characteristic curve.

RESULTS:

The respiratory impedance increased in individuals with chronic obstructive pulmonary disease in all of the studied parameters (Zm, Zi, Ze, Zbi, Zbe, ΔZrs and Zpp). These changes were inversely associated with spirometric parameters. Higher impedances were observed in the expiratory phase of individuals with chronic obstructive pulmonary disease. All of the studied parameters, except for ΔZrs (area under the receiver operating characteristic <0.8), exhibited high accuracy for clinical use (area under the receiver operating characteristic >0.90; Sensibility ≥ 0.85; Sp ≥ 0.85).

CONCLUSIONS:

The respiratory alterations in severe chronic obstructive pulmonary disease may be identified by the increase in respiratory system impedance, which is more evident in the expiratory phase. These results confirm the potential of within-breath analysis of respiratory impedance for the assessment of respiratory modifications related to chronic obstructive pulmonary disease.     

Vasoreactions to acute hypoxia,whole lungs and isolated vessels compared: modulation by NO

We aimed to explain diverse pulmonary vascular responses to hypoxia in different preparations and their modulation by NO. In rats we compared isolated perfused lungs (IPL), small vessels in vitro (PRVs) and in vivo preparations. In IPL and in vivo, acute and chronic nitric oxide synthase (NOS) blockade with L-NAME left normoxic pulmonary artery pressure unchanged but enhanced hypoxic vasoconstriction, hypoxia-induced pulmonary vasoconstriction (HPV). PRVs in vitro, precontracted with PGF(2alpha), showed four tension changes in acute hypoxia: dilatation, contraction, dilatation, contraction. Acute and chronic NOS blockade reduced the first two phases. In non-precontracted PRVs (from other laboratories), NOS inhibition enhanced HPV as in vivo and IPL; attenuation of HPV seems associated with precontraction. Thus reduced NOS activity does not cause pulmonary hypertension but exaggerates HPV. In IPL, prolonged severe hypoxia caused biphasic vasoconstriction separated by dilatation; the time course resembled that seen in PRVs. We suggest that the sequence of events during hypoxia in PRVs can be detected in whole lung preparations.     

Correlation between congenital heart disease complicated with pulmonary artery hypertension and circulating endothelial cells as well as endothelin-1

Objective: To investigate changes in the level of circulating endothelial cells (CECs) and endothelin-1 (ET-1) in peripheral venous blood of the patients with congenital heart disease (CHD) complicated with pulmonary artery hypertension (PAH), and research on their effects in the onset and progress of CHD complicated with PAH. Methods: A case-control study including 30 cases of healthy controls, 15 cases of left-to-right shunt CHD without PAH, 26 cases of CHD complicated with mild PAH, and 17 cases of CHD complicated with moderate-severe PAH was performed. We used flow cytometry to measure the percentage of CECs accounting for nucleated cells in whole blood, and enzyme linked immunosorbent assay (ELISA) to measure the level of ET-1 in serum. The differences of above-mentioned biomarkers between different groups were compared. Results: (1) The level of CECs and ET-1in the group of moderate-severe PAH was significantly higher than those in the group of mild PAH and the group of CHD without PAH. Significantly difference was also observed between the level of CECs and ET-1 in the group of mild PAH and those in the group of CHD without PAH and the control group. Meanwhile, the level of CECs and ET-1 in the group of large shunt was significantly higher than those in the group few shunt and few-medium shunt. (2) Strong positive correlations were observed between pulmonary artery systolic pressure and percentage of CECs as well as ET-1 production. Mean pulmonary artery pressure also positively correlated with percentage of CECs as well as ET-1 production. (3) Arterial partial pressure of oxygen as well as arterial oxygen saturation negatively correlated with the level of CECs, whereas the volume of left-to-right shunt positively correlated with the level of ET-1. (4) The level of CECs and ET-1 were positively correlated as well in CHD patients. Conclusions: CHD complicated with PAH is associated with increased CEC counts and ET-1 production. This study suggests that CECs and ET-1 could be used as clinical biomarkers to define medical strategies for control of PAH.     

Alterations in arterial blood parameters in patients with liver cirrhosis and ascites

In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (V(A)/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO(2)), in oxygen saturation of hemoglobin (SaO(2)) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). Complications were: upper gastrointestinal bleeding 24 (48.97), hepatic encephalopathy 20 (40.81%), gastritis 28 (57.14%), hepatoma 5 (10.2%), renal hepatic syndrome 2 (4.01%), HbsAg (+) 24 (48.97%), and hepatic pleural effusions 7 (14.28%). Average PaO(2) and SaO(2) were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO(2) and SaO(2 )was p<0.01). Respiratory alkalosis, metabolic alkalosis, metabolic acidosis, respiratory acidosis and metabolic acidosis with respiratory alkalosis were acid-base disturbances observed. In conclusion, portopulmonary shunt, intrapulmonary arteriovenous shunt and V(A)/Q inequality can induce a decrease in PaO(2) and SaO(2) as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome.     

Multiple sites of oxygen sensing and their contributions to hypoxic pulmonary vasoconstriction

Oxygen sensing by the pulmonary vasculature is important for the regulation of vessel tone and the matching of lung perfusion to ventilation. Airways hypoxia is a major stimulus for vasoconstriction, which diverts blood from hypoxic alveoli to better ventilated areas of the lung. Several hypotheses have emerged to explain how pulmonary arteries sense a decrease in oxygen and mediate hypoxic pulmonary vasoconstriction (HPV). They differ mainly in where they place the main site of HPV: in the endothelial or smooth muscle cells of the artery wall. HPV probably results from synergistic actions on both cell types, but it can proceed in the absence of endothelium, suggesting that the primary oxygen sensor is the smooth muscle cell and endothelium-derived agents modulate the muscle response. Several oxygen-sensing targets have been identified in smooth muscle, including potassium channels, Ca(2+) stores in the sarcoplasmic reticulum (SR) and the Ca(2+) sensitivity of the contractile proteins. The evidence for different oxygen-sensing mechanisms in pulmonary vessels is discussed.