3D Fluid-Structure Interaction Canine Heart Model with Patch to Quantify Mechanical Conditions for Optimal Myocardium Stem Cell Growth and Tissue Regeneration

Right ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. Myocardial tissue regeneration techniques are being developed for the potential that viable myocardium may be regenerated to replace scar tissues in the heart or used as patch material in heart surgery. 3D computational RV/LV/Patch models with fluid-structure interactions (FSI) were constructed based on data from a healthy dog heart to obtain local fluid dynamics and structural stress/strain information and identify optimal conditions under which tissue regeneration techniques could achieve best outcome. RV/LV/Patch geometry and blood pressure data were obtained from a dog following established procedures. Four FSI models were used to quantify the influence of different patch materials (Dacron scaffold, treated pericardium) on local environment around the patch area, especially focusing on the thickness and stiffness of the patch. Our results indicated that changes in patch stiffness had little impact on the ejection fraction of the right ventricle because the total patch area was small. However, patch stiffness had huge impact on local RV maximum principal stress (Stress-P1) and strain (Strain-P1) around the patch area. Compared to the no-patch model, patch models had increased Stress-P1 and decreased Strain-P1 values in the patch area. Softer patches were associated with greater stress/strain variations. Thinner patch led to complex local flow environment which may have impact on myocytes seeding and RV remodeling. Our multi-physics RV/LV/Patch FSI model can serve as a useful tool to investigate cellular biology and tissue regeneration under localized flow and structural stress environment.     

An anisotropic constitutive model for immersogeometric fluid–structure interaction analysis of bioprosthetic heart valves

This paper considers an anisotropic hyperelastic soft tissue model, originally proposed for native valve tissue and referred to herein as the Lee–Sacks model, in an isogeometric thin shell analysis framework that can be readily combined with immersogeometric fluid–structure interaction (FSI) analysis for high-fidelity simulations of bioprosthetic heart valves (BHVs) interacting with blood flow. We find that the Lee–Sacks model is well-suited to reproduce the anisotropic stress–strain behavior of the cross-linked bovine pericardial tissues that are commonly used in BHVs. An automated procedure for parameter selection leads to an instance of the Lee–Sacks model that matches biaxial stress–strain data from the literature more closely, over a wider range of strains, than other soft tissue models. The relative simplicity of the Lee–Sacks model is attractive for computationally-demanding applications such as FSI analysis and we use the model to demonstrate how the presence and direction of material anisotropy affect the FSI dynamics of BHV leaflets.     

A tidal breathing model for the multiple inert gas elimination technique.

The tidal breathing lung model described for the sine-wave technique (D. J. Gavaghan and C. E. W. Hahn. Respir. Physiol. 106: 209-221, 1996) is generalized to continuous ventilation-perfusion and ventilation-volume distributions. This tidal breathing model is then applied to the multiple inert gas elimination technique (P. D. Wagner, H. A. Saltzman, and J. B. West. J. Appl. Physiol. 36: 588-599, 1974). The conservation of mass equations are solved, and it is shown that 1) retentions vary considerably over the course of a breath, 2) the retentions are dependent on alveolar volume, and 3) the retentions depend only weakly on the width of the ventilation-volume distribution. Simulated experimental data with a unimodal ventilation-perfusion distribution are inserted into the parameter recovery model for a lung with 1 or 2 alveolar compartments and for a lung with 50 compartments. The parameters recovered using both models are dependent on the time interval over which the blood sample is taken. For best results, the blood sample should be drawn over several breath cycles.     

High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion

Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O(2)) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130(Cas). RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.     

Pulmonary responses of conscious strain 13 guinea pigs to Pichinde viral infection.

A laboratory animal model for studying pulmonary responses to arenaviral infection was established with advanced technologies. Tidal volume (TV), respiratory rate (RR), minute volume (MV), expiratory time (TE), inspiratory time (TI), peak expiratory flow (PEF), and specific pulmonary airway resistance (RES) were measured with a double plethysmograph and a computer data-acquisition system in six conscious, strain 13 guinea pigs. Using the same animal, experiments were conducted before and after subcutaneous inoculation with 10(4) plaque-forming units of Pichinde virus. Pulmonary functions were determined for 1 minute every 10 minutes for 2 hours before and at postinoculation days (PID) 3, 6, 8, and daily thereafter until shortly before death. The mean time to death was 18 +/- 0.7 days. Tidal volume, RR, MV, PEF, RES, and rectal temperature increased slightly on PID 3 and reached peak values at the midpoint of disease. At 95% of the mean time to death (16.5 +/- 0.5 days), RR, MV, and rectal temperatures suddenly decreased to lower than baseline values; while TV, RES, and PEF values remained high. When TE decreased with the increase in RR, TI did not change. When RR decreased at the terminal stage, both TE and TI increased. Hyperventilation, increased specific pulmonary airway resistance, terminal hypoventilation, and respiratory arrest were noted in strain 13 guinea pigs infected with Pichinde virus.     

Finite element analysis of ramming in Ovis canadensis

The energy produced during the ramming of bighorn sheep (Ovis canadensis) would be expected to result in undesirable stresses in their frontal skull, which in turn would cause brain injury; yet, this animal seems to suffer no ill effects. In general, horn is made of an α-keratin sheath covering a bone. Despite volumes of data on the ramming behavior of Ovis canadensis, the extent to which structural components of horn and horn-associated structure or tissue absorb the impact energy generated by the ramming event is still unknown. This study investigates the hypothesis that there is a mechanical relationship present among the ramming event, the structural constituents of the horn, and the horn-associated structure. The three-dimensional complex structure of the bighorn sheep horn was successfully constructed and modeled using a computed tomography (CT) scan and finite element (FE) method, respectively. Three different three-dimensional quasi-static models, including a horn model with trabecular bone, a horn model with compact bone that instead of trabecular bone, and a horn model with trabecular bone as well as frontal sinuses, were studied. FE simulations were used to compare distributions of principal stress in the horn and the frontal sinuses and the strain energy under quasi-static loading conditions. It was noticed that strain energy due to elastic deformation of the complex structure of horn modeled with trabecular bone and with trabecular bone and frontal sinus was different. In addition, trabecular bone in the horn distributes the stresses over a larger volume, suggesting a mechanical link between the structural constituents and the ramming event. This phenomenon was elucidated through the principal stress distribution in the structure. This study will help designers in choosing appropriate material combinations for the successful design of protective structures against a similar impact.     

Development of a phantom for dose distribution verification in Stereotactic Radiosurgery

A geometric acrylic phantom was designed and built for dose distribution verification in Stereotactic Radiosurgery. Acrylic objects representing the tumor tissue, (target volume (TV)), and the organ at risk (OAR), the brainstem, were inserted inside this phantom. The TV is represented by two semi-spheres of acrylic with a diameter of 13.0 mm, both having a central cavity for accommodation of a TLD-100 detector and a small radiochromic Gafchromic EBT film. The OAR is represented by the two parts of a 38.0 mm length acrylic cylinder with a diameter 18.0 mm and cavities along the cylinder central axis able to accommodate 5 TLD – 100 detectors and another of EBT film between the two cylinder parts. This experimental setup was submitted to a radiosurgical treatment, after which the TL dosimeters were evaluated and their responses were compared with the planned dose values. The radiochromic EBT films showed the dose distributions. The linear accelerator used was a Varian 2300 C/D, generating a 6 MV photon beam. The investigated phantom system was able to check the accuracy of dose delivery to predetermined points and the dose distribution due to stereotactic radiosurgery treatments and proved to be a good tool for quality control in these situations.     

Physiological responses to spirometer load

A transient time-dependent increase in tidal volume (TV) and respiratory rate has been observed as a spirometric loading effect in experiments on 22 decerebrate cats. Respiration was recorded via the impedance pneumograph throughout the entire experiment while tidal volume was measured at intervals of 10-60 min on a spirometer. A total of 233 spirograms was recorded. The mean control tidal volume was 14 ml/kg, followed by an average increase of 30%, 43%, 51%, and 64% at 30, 60, 90, and 120 sec on the spirometer respectively. Spirometric respiratory rate also increased and as a result instantaneous minute volumes (MV) showed increases up to nearly 400% of control. Maximal effects occurred within 80 sec reflecting a sequential combination of reflex (via vagal afferents) and chemical (increased CO2) factors reaching a new equilibrium. We also noted a spirometric regularization of previously irregular or periodic (Biot's) breathing. It is apparent that the spirometer introduces small and graded perturbations into respiratory control systems.     

A Numerical Study of Local Variations in Tidal Regime of Tagus Estuary,Portugal

Tidal dynamics of shallow estuaries and lagoons is a complex matter that has attracted the attention of a large number of researchers over the last few decades. The main purpose of the present work is to study the intricate tidal dynamics of the Tagus estuary, which states as the largest estuary of the Iberian Peninsula and one of the most important wetlands in Portugal and Europe. Tagus has large areas of low depth and a remarkable geomorphology, both determining the complex propagation of tidal waves along the estuary of unknown manner. A non-linear two-dimensional vertically integrated hydrodynamic model was considered to be adequate to simulate its hydrodynamics and an application developed from the SIMSYS2D model was applied to study the tidal propagation along the estuary. The implementation and calibration of this model revealed its accuracy to predict tidal properties along the entire system. Several model runs enabled the analysis of the local variations in tidal dynamics, through the interpretation of amplitude and phase patterns of the main tidal constituents, tidal asymmetry, tidal ellipses, form factor and tidal dissipation. Results show that Tagus estuary tidal dynamics is extremely dependent on an estuarine resonance mode for the semi-diurnal constituents that induce important tidal characteristics. Besides, the estuarine coastline features and topography determines the changes in tidal propagation along the estuary, which therefore result essentially from a balance between convergence/divergence and friction and advection effects, besides the resonance effects.     

Effects of vagus nerve stimulation and vagotomy on systemic and pulmonary inflammation in a two-hit model in rats

Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit) may be potentiated by mechanical ventilation (MV, second hit). Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX) and vagus nerve stimulation (VNS) on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS) and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg) or moderate (15 mL/kg) tidal volumes was initiated, or animals were left breathing spontaneously (SP). After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP), but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM), and resulted in decreased pO(2) (p<0.05 compared to sham-operated animals). VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.     

Cellular Automata Modeling of Pulmonary Inflammation

Better understanding of the acute/chronic inflammation in airways is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Local lung inflammation is triggered by many mechanisms within the lung, including pathogens. In this study, a cellular automata based model (CA) for pulmonary inflammation that incorporates biophysical processes during inflammatory responses was developed. The developed CA results in three possible outcomes related to homeostasis (healing), persistent infection, and resolved infection with high inflammation (inflamed state). The results from the model are validated qualitatively against other existing computational models. A sensitivity analysis was conducted on the model parameters and the outcomes were assessed. Overall, the model results showed possible outcomes that have been seen in clinical practice and animal models. The present model can be extended to include inflammation resulting from damage tissue and eventually to model inflammation resulting from acute lung injury and multiple organ dysfunction syndromes in critical illness and injury.     

Partitioning of pulmonary resistance in dogs: effect of tidal volume and frequency

To determine the sensitivity of pulmonary resistance (RL) to changes in breathing frequency and tidal volume, we measured RL in intact anesthetized dogs over a range of breathing frequencies and tidal volumes centering around those encountered during quiet breathing. To investigate mechanisms responsible for changes in RL, the relative contribution of airway resistance (Raw) and tissue resistance (Rti) to RL at similar breathing frequencies and tidal volumes was studied in six excised, exsanguinated canine left lungs. Lung volume was sinusoidally varied, with tidal volumes of 10, 20, and 40% of vital capacity. Pressures were measured at three alveolar sites (PA) with alveolar capsules and at the airway opening (Pao). Measurements were made during oscillation at five frequencies between 5 and 45 min-1 at each tidal volume. Resistances were calculated by assuming a linear equation of motion and submitting lung volume, flow, Pao, and PA to a multiple linear regression. RL decreased with increasing frequency and decreased with increasing tidal volume in both isolated and intact lungs. In isolated lungs, Rti decreased with increasing frequency but was independent of tidal volume. Raw was independent of frequency but decreased with tidal volume. The contribution of Rti to RL ranged from 93 +/- 4% (SD) with low frequency and large tidal volume to 41 +/- 24% at high frequency and small tidal volume. We conclude that the RL is highly dependent on breathing frequency and less dependent on tidal volume during conditions similar to quiet breathing and that these findings are explained by changes in the relative contributions of Raw and Rti to RL.     

Numerical simulation of two-phase non-Newtonian blood flow with fluid-structure interaction in aortic dissection

The behavior of blood cells and vessel compliance significantly influence hemodynamic parameters, which are closely related to the development of aortic dissection. Here the two-phase non-Newtonian model and the fluid-structure interaction (FSI) method are coupled to simulate blood flow in a patient-specific dissected aorta. Moreover, three-element Windkessel model is applied to reproduce physiological pressure waves. Important hemodynamic indicators, such as the spatial distribution of red blood cells (RBCs) and vessel wall displacement, which greatly influence the hemodynamic characteristics are analyzed. Results show that the proximal false lumen near the entry tear appears to be a vortex zone with a relatively lower volume fraction of RBCs, a low time-averaged wall shear stress (TAWSS) and a high oscillatory shear index (OSI), providing a suitable physical environment for the formation of atherosclerosis. The highest TAWSS is located in the narrow area of the distal true lumen which might cause further dilation. TAWSS distributions in the FSI model and the rigid wall model show similar trend, while there is a significant difference for the OSI distributions. We suggest that an integrated model is essential to simulate blood flow in a more realistic physiological environment with the ultimate aim of guiding clinical treatment.     

Viscoelastic behavior of a lung alveolar duct model

A study is conducted into the oscillatory behavior of a finite element model of an alveolar duct. Its load-bearing components consist of a network of elastin and collagen fibers and surface tension acting over the air-liquid interfaces. The tissue is simulated using a visco-elastic model involving nonlinear quasi-static stress-strain behavior combined with a reduced relaxation function. The surface tension force is simulated with a time- and area-dependent model of surfactant behavior. The model was used to simulate lung parenchyma under three surface tension cases: air-filled, liquid-filled, and lavaged with 3-dimenthyl siloxane, which has a constant surface tension of 16 dyn/cm. The dynamic elastance (Edyn) and tissue resistance (Rti) were computed for sinusoidal tidal volume oscillations over a range of frequencies from 0.16-2.0 Hz. A comparison of the variation of Edyn and Rti with frequency between the model and published experimental data showed good qualitative agreement. Little difference was found in the model between Rti for the air-filled and lavaged models; in contrast, published data revealed a significantly higher value of Rti in the lavaged lung. The absence of a significant increase in Rti for the lavaged model can be attributed to only minor changes in the individual fiber bundle resistances with changes in their configuration. The surface tension was found to make an important contribution to both Edyn and Rti in the air-filled duct model. It was also found to amplify any existing tissue dissipative properties, despite exhibiting none itself over the small tidal volume cycles examined.     

Characterizing airway and alveolar nitric oxide exchange during tidal breathing using a three-compartment model.

Exhaled nitric oxide (NO) may be a useful marker of lung inflammation, but the concentration is highly dependent on exhalation flow rate due to a significant airway source. Current methods for partitioning pulmonary NO gas exchange into airway and alveolar regions utilize multiple exhalation flow rates or a single-breath maneuver with a preexpiratory breath hold, which is cumbersome for children and individuals with compromised lung function. Analysis of tidal breathing data has the potential to overcome these limitations, while still identifying region-specific parameters. In six healthy adults, we utilized a three-compartment model (two airway compartments and one alveolar compartment) to identify two potential flow-independent parameters that represent the average volumetric airway flux (pl/s) and the time-averaged alveolar concentration (parts/billion). Significant background noise and distortion of the signal from the sampling system were compensated for by using a Gaussian wavelet filter and a series of convolution integrals. Mean values for average volumetric airway flux and time-averaged alveolar concentration were 2,500 +/- 2,700 pl/s and 3.2 +/- 3.4 parts/billion, respectively, and were strongly correlated with analogous parameters determined from vital capacity breathing maneuvers. Analysis of multiple tidal breaths significantly reduced the standard error of the parameter estimates relative to the single-breath technique. Our initial assessment demonstrates the potential of utilizing tidal breathing for noninvasive characterization of pulmonary NO exchange dynamics.     

大潮气量致急性肺损伤犬呼吸机相关性肺损伤模型的构建

目的建立大潮气量致急性肺损伤（ALI）犬呼吸机相关性肺损伤（VILI）模型。方法健康雄性杂种犬12只用油酸静脉注射法制备犬ALI模型,造模成功后进行支持通气15min过渡,然后随机分为VILI组及对照组行机械通气6 h,每组6只。VILI组潮气量（Vt）=20 mL/kg,对照组Vt=6 mL/kg,两组呼气末正压（PEEP）均为10 cmH2O。动态观察各组血气交换指标变化。通气6 h后取支气管肺泡灌洗液（BALF）作白蛋白浓度检查,取肺组织作病理切片肺损伤评分。结果各组在油酸静脉注射后（2.50±0.80）h达到ALI标准。VILI组在犬机械通气6 h后PaO2、SaO2及氧合指数（OI）较对照组略下降（P〈0.05）,而PaCO2波动不大,且心率、血压波动也较对照组小（P〈0.05）。VILI组BALF中蛋白浓度和肺组织损伤评分均较对照组显著升高（分别P〈0.05,P〈0.01）。结论本实验成功建立了大潮气量致ALI犬VILI模型。     

Normalization of Ventilation Data from 4D-CT to Facilitate Comparison between Datasets Acquired at Different Times

Purpose

The 4D-CT data used for comparing a patient’s ventilation distributions before and after lung radiotherapy are acquired at different times. As a result, an additional variable – the tidal volume (TV) – can alter the results. Therefore, in this paper we propose to normalize the ventilation to the same TV to eliminate that uncertainty.

Methods

Absolute ventilation (AV) data were generated for 6 stereotactic body radiation therapy (SBRT) cases before and after treatment, using the direct geometric algorithm and diffeomorphic morphons deformable image registration (DIR). Each pair of AV distributions was converted to TV-normalized, percentile ventilation (PV) and low-dose well-ventilated-normalized ventilation (LDWV) distributions. The ventilation change was calculated in various dose regions based on the treatment plans using the DIR-registered before and after treatment data sets. The ventilation change based on TV-normalized ventilation was compared with the AV as well as the data normalized by PV and LDWV.

Results

AV change may be misleading when the TV differs before and after treatment, which was found to be up to 6.7%. All three normalization methods produced a similar trend in ventilation change: the higher the dose to a region of lung, the greater the degradation in ventilation. In low dose regions (<5 Gy), ventilation appears relatively improved after treatment due to the relative nature of the normalized ventilation. However, the LDWV may not be reliable when the ventilation in the low-dose regions varies. PV exhibited a similar ventilation change trend compared to the TV-normalized in all cases. However, by definition, the ventilation distribution in the PV is significantly different from the original distribution.

Conclusion

Normalizing ventilation distributions by the TV is a simple and reliable method for evaluation of ventilation changes.     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

Low tidal volume protects pulmonary vasomotor function from “second-hit” injury in acute lung injury rats

Background

Sepsis could induce indirect acute lung injury(ALI), and pulmonary vasomotor dysfunction. While low tidal volume is advocated for treatment of ALI patients. However, there is no evidence for low tidal volume that it could mitigate pulmonary vasomotor dysfunction in indirect ALI. Our study is to evaluate whether low tidal volume ventilation could protect the pulmonary vascular function in indirect lipopolysaccharide (LPS) induced acute lung injury rats.

Methods

An indirect ALI rat model was induced by intravenous infusion of LPS. Thirty rats (n = 6 in each group) were randomly divided into (1)Control group; (2) ALI group; (3) LV group (tidal volume of 6mL/kg); (4) MV group (tidal volume of 12mL/kg); (5)VLV group (tidal volume of 3mL/kg). Mean arterial pressure and blood gas analysis were monitored every 2 hours throughout the experiment. Lung tissues and pulmonary artery rings were immediately harvested after the rats were bled to be killed to detect the contents of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and TNF-α. Acetylcholine (Ache)-induced endothelium-dependent and sodium nitroprusside (SNP)-induced endothelium-independent relaxation of isolated pulmonary artery rings were measured by tensiometry.

Results

There was no difference within groups concerning blood pressure, PaCO₂ and SNP-induced endothelium-independent relaxation of pulmonary artery rings. Compared with MV group, LV group significantly reduced LPS-induced expression of ET-1 level (113.79 ± 7.33pg/mL vs. 152.52 ± 12.75pg/mL, P < 0.05) and TNF-α (3305.09 ± 334.29pg/mL vs.4144.07 ± 608.21pg/mL, P < 0.05), increased the expression of eNOS (IOD: 15032.05 ± 5925.07 vs. 11454.32 ± 6035.47, P < 0.05). While Ache (10^-7mol/L-10^-4mol/L)-induced vasodilatation was ameliorated 30% more in LV group than in MV group.

Conclusions

Low tidal volume could protect the pulmonary vasodilative function during indirect ALI by decreasing vasoconstrictor factors, increasing expressions of vasodilator factors in pulmonary endothelial cells, and inhibiting inflammation injuries.