The paradox of adult respiratory distress syndrome in neonates

Six full-term newborn infants are described who suffered from severe adult respiratory distress syndrome (ARDS). The triggering event was intrauterine/perinatal asphyxia in five, and group B streptococcal (GBS) septicemia in three. All had severe respiratory distress/failure and were ventilated mechanically with high concentrations of inspired oxygen and positive end-expiratory pressure. Radiography of the chest showed dense bilateral consolidation with air bronchograms and reduced lung volume. Persistent pulmonary hypertension (PPH) was documented in all cases. The coincidence of ARDS and PPH rendered respiratory management extremely difficult. For this reason high-frequency ventilation was instituted in all patients in order to improve CO2 elimination and induce respiratory alkalosis. Acute complications of respiratory therapy were encountered in five patients (pneumothorax, pulmonary interstitial emphysema, pneumopericardium). Three infants died (irreversible septic shock, progressive severe hypoxemia, and sudden cardiac arrest) after 17, 80, and 175 h of life. Histologic examination of the lungs was possible in all fatal cases and revealed typical changes of acute to subacute stages of ARDS. Three infants survived, the mean time of mechanical respiratory support being 703 h. Two patients were still dependent on oxygen after 1 month of life, and all survivors had increased interstitial markings and increased lung volumes on their chest roentgenograms at this time.

SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice

Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and chronic bronchitis and is a leading cause of morbidity and mortality worldwide. Tobacco smoke and deficiency in α1-antitrypsin (AAT) are the most prominent environmental and genetic risk factors, respectively. Yet the pathogenesis of COPD is not completely elucidated. Disease progression appears to include a vicious circle driven by self-perpetuating lung inflammation, endothelial and epithelial cell death, and proteolytic degradation of extracellular matrix proteins. Like AAT, serpinB1 is a potent inhibitor of serine proteases including neutrophil elastase and cathepsin G. Because serpinB1 is expressed in myeloid and lung epithelial cells and is protective during lung infections, we investigated the role of serpinB1 in preventing age-related and cigarette smoke-induced emphysema in mice. Fifteen-month-old mice showed increased lung volume and decreased pulmonary function compared with young adult mice (3 mo old), but no differences were observed between serpinB1-deficient (KO) and wild-type (WT) mice. Chronic exposure to secondhand cigarette smoke resulted in structural emphysematous changes compared with respective control mice, but no difference in lung morphometry was observed between genotypes. Of note, the different pattern of stereological changes induced by age and cigarette smoke suggest distinct mechanisms leading to increased airway volume. Finally, expression of intracellular and extracellular protease inhibitors were differently regulated in lungs of WT and KO mice following smoke exposure; however, activity of proteases was not significantly altered. In conclusion, we showed that, although AAT and serpinB1 are similarly potent inhibitors of neutrophil proteases, serpinB1 deficiency is not associated with more severe emphysema.

Beamlet based direct aperture optimization for MERT using a photon MLC

PURPOSE A beamlet based direct aperture optimization (DAO) for modulated electron radiotherapy (MERT) using photon multileaf collimator (pMLC) shaped electron fields is developed and investigated. METHODS The Swiss Monte Carlo Plan (SMCP) allows the calculation of dose distributions for pMLC shaped electron beams. SMCP is interfaced with the Eclipse TPS (Varian Medical Systems, Palo Alto, CA) which can thus be included into the inverse treatment planning process for MERT. This process starts with the import of a CT-scan into Eclipse, the contouring of the target and the organs at risk (OARs), and the choice of the initial electron beam directions. For each electron beam, the number of apertures, their energy, and initial shape are defined. Furthermore, the DAO requires dose-volume constraints for the structures contoured. In order to carry out the DAO efficiently, the initial electron beams are divided into a grid of beamlets. For each of those, the dose distribution is precalculated using a modified electron beam model, resulting in a dose list for each beamlet and energy. Then the DAO is carried out, leading to a set of optimal apertures and corresponding weights. These optimal apertures are now converted into pMLC shaped segments and the dose calculation for each segment is performed. For these dose distributions, a weight optimization process is launched in order to minimize the differences between the dose distribution using the optimal apertures and the pMLC segments. Finally, a deliverable dose distribution for the MERT plan is obtained and loaded back into Eclipse for evaluation. For an idealized water phantom geometry, a MERT treatment plan is created and compared to the plan obtained using a previously developed forward planning strategy. Further, MERT treatment plans for three clinical situations (breast, chest wall, and parotid metastasis of a squamous cell skin carcinoma) are created using the developed inverse planning strategy. The MERT plans are compared to clinical standard treatment plans using photon beams and the differences between the optimal and the deliverable dose distributions are determined. RESULTS For the idealized water phantom geometry, the inversely optimized MERT plan is able to obtain the same PTV coverage, but with an improved OAR sparing compared to the forwardly optimized plan. Regarding the right-sided breast case, the MERT plan is able to reduce the lung volume receiving more than 30% of the prescribed dose and the mean lung dose compared to the standard plan. However, the standard plan leads to a better homogeneity within the CTV. The results for the left-sided thorax wall are similar but also the dose to the heart is reduced comparing MERT to the standard treatment plan. For the parotid case, MERT leads to lower doses for almost all OARs but to a less homogeneous dose distribution for the PTV when compared to a standard plan. For all cases, the weight optimization successfully minimized the differences between the optimal and the deliverable dose distribution. CONCLUSIONS A beamlet based DAO using multiple beam angles is implemented and successfully tested for an idealized water phantom geometry and clinical situations.

Forward treatment planning for modulated electron radiotherapy (MERT) employing Monte Carlo methods

PURPOSE This paper describes the development of a forward planning process for modulated electron radiotherapy (MERT). The approach is based on a previously developed electron beam model used to calculate dose distributions of electron beams shaped by a photon multi leaf collimator (pMLC). METHODS As the electron beam model has already been implemented into the Swiss Monte Carlo Plan environment, the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) can be included in the planning process for MERT. In a first step, CT data are imported into Eclipse and a pMLC shaped electron beam is set up. This initial electron beam is then divided into segments, with the electron energy in each segment chosen according to the distal depth of the planning target volume (PTV) in beam direction. In order to improve the homogeneity of the dose distribution in the PTV, a feathering process (Gaussian edge feathering) is launched, which results in a number of feathered segments. For each of these segments a dose calculation is performed employing the in-house developed electron beam model along with the macro Monte Carlo dose calculation algorithm. Finally, an automated weight optimization of all segments is carried out and the total dose distribution is read back into Eclipse for display and evaluation. One academic and two clinical situations are investigated for possible benefits of MERT treatment compared to standard treatments performed in our clinics and treatment with a bolus electron conformal (BolusECT) method. RESULTS The MERT treatment plan of the academic case was superior to the standard single segment electron treatment plan in terms of organs at risk (OAR) sparing. Further, a comparison between an unfeathered and a feathered MERT plan showed better PTV coverage and homogeneity for the feathered plan, with V95% increased from 90% to 96% and V107% decreased from 8% to nearly 0%. For a clinical breast boost irradiation, the MERT plan led to a similar homogeneity in the PTV compared to the standard treatment plan while the mean body dose was lower for the MERT plan. Regarding the second clinical case, a whole breast treatment, MERT resulted in a reduction of the lung volume receiving more than 45% of the prescribed dose when compared to the standard plan. On the other hand, the MERT plan leads to a larger low-dose lung volume and a degraded dose homogeneity in the PTV. For the clinical cases evaluated in this work, treatment plans using the BolusECT technique resulted in a more homogenous PTV and CTV coverage but higher doses to the OARs than the MERT plans. CONCLUSIONS MERT treatments were successfully planned for phantom and clinical cases, applying a newly developed intuitive and efficient forward planning strategy that employs a MC based electron beam model for pMLC shaped electron beams. It is shown that MERT can lead to a dose reduction in OARs compared to other methods. The process of feathering MERT segments results in an improvement of the dose homogeneity in the PTV.

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

OBJECTIVE Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. METHODS Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). RESULTS The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. CONCLUSIONS In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF6) and helium (He) using an ultrasonic flowmeter (USFM). Methods The tracer gas mixture contained 5% SF6 and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart. Results USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF6 and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%. Conclusion The USFM accurately measured relative changes in SF6 and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF6 and He washout patterns during tidal breathing.

Volumetric analysis of lung nodules in computed tomography (CT): comparison of two different segmentation algorithm softwares and two different reconstruction filters on automated volume calculation.

BACKGROUND A precise detection of volume change allows for better estimating the biological behavior of the lung nodules. Postprocessing tools with automated detection, segmentation, and volumetric analysis of lung nodules may expedite radiological processes and give additional confidence to the radiologists. PURPOSE To compare two different postprocessing software algorithms (LMS Lung, Median Technologies; LungCARE®, Siemens) in CT volumetric measurement and to analyze the effect of soft (B30) and hard reconstruction filter (B70) on automated volume measurement. MATERIAL AND METHODS Between January 2010 and April 2010, 45 patients with a total of 113 pulmonary nodules were included. The CT exam was performed on a 64-row multidetector CT scanner (Somatom Sensation, Siemens, Erlangen, Germany) with the following parameters: collimation, 24x1.2 mm; pitch, 1.15; voltage, 120 kVp; reference tube current-time, 100 mAs. Automated volumetric measurement of each lung nodule was performed with the two different postprocessing algorithms based on two reconstruction filters (B30 and B70). The average relative volume measurement difference (VME%) and the limits of agreement between two methods were used for comparison. RESULTS At soft reconstruction filters the LMS system produced mean nodule volumes that were 34.1% (P < 0.0001) larger than those by LungCARE® system. The VME% was 42.2% with a limit of agreement between -53.9% and 138.4%.The volume measurement with soft filters (B30) was significantly larger than with hard filters (B70); 11.2% for LMS and 1.6% for LungCARE®, respectively (both with P < 0.05). LMS measured greater volumes with both filters, 13.6% for soft and 3.8% for hard filters, respectively (P < 0.01 and P > 0.05). CONCLUSION There is a substantial inter-software (LMS/LungCARE®) as well as intra-software variability (B30/B70) in lung nodule volume measurement; therefore, it is mandatory to use the same equipment with the same reconstruction filter for the follow-up of lung nodule volume.

Effectiveness of nitric oxide during spontaneous breathing in experimental lung injury

Inhaled nitric oxide (iNO) improves gas exchange in about 60% of patients with acute respiratory distress syndrome (ARDS). Recruitment of atelectatic lung areas may improve responsiveness and preservation of spontaneous breathing (SB) may cause recruitment. Accordingly, preservation of SB may improve effectiveness of iNO. To test this hypothesis, iNO was evaluated in experimental acute lung injury (ALI) during SB. In 24 pigs with ALI, effects of 10 ppm iNO were evaluated during controlled mechanical ventilation (CMV) and SB in random order. Preservation of SB was provided by 4 different modes: Unassisted SB was enabled by biphasic positive airway pressure (BIPAP), moderate inspiratory assist was provided by pressure support (PS) and volume-assured pressure support (VAPS), maximum assist was ensured by assist control (A/C). Statistical analysis did not reveal gas exchange improvements due to SB alone. Significant gas exchange improvements due to iNO were only achieved during unassisted SB with BIPAP (P <.05) but not during CMV or assisted SB. The authors conclude that effectiveness of iNO may be improved by unassisted SB during BIPAP but not by assisted SB. Thus combined iNO and unassisted SB is possibly most effective to improve gas exchange in severe hypoxemic ARDS.

Normative data for lung function and exhaled nitric oxide in unsedated healthy infants

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean ± sd age of 5.1 ± 0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (R(int)) measurements. Acceptable measurements were obtained in ≤ 285 infants with high variability. Mean values were 7.48 mL·kg⁻¹ (95% limits of agreement 4.95-10.0 mL·kg⁻¹) for tidal volume, 14.3 ppb (2.6-26.1 ppb) for eNO, 23.9 mL·kg⁻¹ (16.0-31.8 mL·kg⁻¹) for functional residual capacity, 6.75 (5.63-7.87) for lung clearance index and 3.78 kPa·s·L⁻¹ (1.14-6.42 kPa·s·L⁻¹) for R(int). In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

Impact of aerobic exercise capacity and procedure-related factors in lung cancer surgery

Over the past decades, major progress in patient selection, surgical techniques and anaesthetic management have largely contributed to improved outcome in lung cancer surgery. The purpose of this study was to identify predictors of post-operative cardiopulmonary morbidity in patients with a forced expiratory volume in 1 s <80% predicted, who underwent cardiopulmonary exercise testing (CPET). In this observational study, 210 consecutive patients with lung cancer underwent CPET with completed data over a 9-yr period (2001-2009). Cardiopulmonary complications occurred in 46 (22%) patients, including four (1.9%) deaths. On logistic regression analysis, peak oxygen uptake (peak V'(O₂) and anaesthesia duration were independent risk factors of both cardiovascular and pulmonary complications; age and the extent of lung resection were additional predictors of cardiovascular complications, whereas tidal volume during one-lung ventilation was a predictor of pulmonary complications. Compared with patients with peak V'(O₂) >17 mL·kg⁻¹·min⁻¹, those with a peak V'(O₂) <10 mL·kg⁻¹·min⁻¹ had a four-fold higher incidence of cardiac and pulmonary morbidity. Our data support the use of pre-operative CPET and the application of an intra-operative protective ventilation strategy. Further studies should evaluate whether pre-operative physical training can improve post-operative outcome.

Influence of fluid and volume state on PaO(2) oscillations in mechanically ventilated pigs

ABSTRACT Varying pulmonary shunt fractions during the respiratory cycle cause oxygen oscillations during mechanical ventilation. In artificially damaged lungs, cyclical recruitment of atelectasis is responsible for varying shunt according to published evidence. We introduce a complimentary hypothesis that cyclically varying shunt in healthy lungs is caused by cyclical redistribution of pulmonary perfusion. Administration of crystalloid or colloid infusions would decrease oxygen oscillations if our hypothesis was right. Therefore, n = 14 mechanically ventilated healthy pigs were investigated in 2 groups: crystalloid (fluid) versus no-fluid administration. Additional volume interventions (colloid infusion, blood withdrawal) were carried out in each pig. Intra-aortal PaO(2) oscillations were recorded using fluorescence quenching technique. Phase shift of oxygen oscillations during altered inspiratory to expiratory (I:E) ventilation ratio and electrical impedance tomography (EIT) served as control methods to exclude that recruitment of atelectasis is responsible for oxygen oscillations. In hypovolemia relevant oxygen oscillations could be recorded. Fluid and volume state changed PaO(2) oscillations according to our hypothesis. Fluid administration led to a mean decline of 105.3 mmHg of the PaO(2) oscillations amplitude (P < 0.001). The difference of the amplitudes between colloid administration and blood withdrawal was 62.4 mmHg in pigs not having received fluids (P = 0.0059). Fluid and volume state also changed the oscillation phase during altered I:E ratio. EIT excluded changes of regional ventilation (i.e., recruitment of atelectasis) to be responsible for these oscillations. In healthy pigs, cyclical redistribution of pulmonary perfusion can explain the size of respiratory-dependent PaO(2) oscillations.

Cell-specific expression of human HGF by alveolar type II cells induces remodeling of septal wall tissue in the lung: a morphometric study

Hepatocyte growth factor (HGF) is involved in development and regeneration of the lungs. Human HGF, which was expressed specifically by alveolar epithelial type II cells after gene transfer, attenuated the bleomycin-induced pulmonary fibrosis in an animal model. As there are also regions that appear morphologically unaffected in fibrosis, the effects of this gene transfer to normal lungs is of interest. In vitro studies showed that HGF inhibits the formation of the basal lamina by cultured alveolar epithelial cells. Thus we hypothesized that, in the healthy lung, cell-specific expression of HGF induces a remodeling within septal walls. Electroporation of a plasmid of human HGF gene controlled by the surfactant protein C promoter was applied for targeted gene transfer. Using design-based stereology at light and electron microscopic level, structural alterations were analyzed and compared with a control group. HGF gene transfer increased the volume of distal air spaces, as well as the surface area of the alveolar epithelium. The volume of septal walls, as well as the number of alveoli, was unchanged. Volumes per lung of collagen and elastic fibers were unaltered, but a marked reduction of the volume of residual extracellular matrix (all components other than collagen and elastic fibers) and interstitial cells was found. A correlation between the volumes of residual extracellular matrix and distal air spaces, as well as total surface area of alveolar epithelium, could be established. Cell-specific expression of HGF leads to a remodeling of the connective tissue within the septal walls in the healthy lung, which is associated with more pronounced stretching of distal air spaces at a given hydrostatic pressure during instillation fixation.

Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V (T)s at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V (T) and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p < 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V (T).

In vivo electroporation and ubiquitin promoter--a protocol for sustained gene expression in the lung

BACKGROUND: Gene therapy applications require safe and efficient methods for gene transfer. Present methods are restricted by low efficiency and short duration of transgene expression. In vivo electroporation, a physical method of gene transfer, has evolved as an efficient method in recent years. We present a protocol involving electroporation combined with a long-acting promoter system for gene transfer to the lung. METHODS: The study was designed to evaluate electroporation-mediated gene transfer to the lung and to analyze a promoter system that allows prolonged transgene expression. A volume of 250 microl of purified plasmid DNA suspended in water was instilled into the left lung of anesthetized rats, followed by left thoracotomy and electroporation of the exposed left lung. Plasmids pCiKlux and pUblux expressing luciferase under the control of the cytomegalovirus immediate-early promoter/enhancer (CMV-IEPE) or human polyubiquitin c (Ubc) promoter were used. Electroporation conditions were optimized with four pulses (200 V/cm, 20 ms at 1 Hz) using flat plate electrodes. The animals were sacrificed at different time points up to day 40, after gene transfer. Gene expression was detected and quantified by bioluminescent reporter imaging (BLI) and relative light units per milligram of protein (RLU/mg) was measured by luminometer for p.Pyralis luciferase and immunohistochemistry, using an anti-luciferase antibody. RESULTS: Gene expression with the CMV-IEPE promoter was highest 24 h after gene transfer (2932+/-249.4 relative light units (RLU)/mg of total lung protein) and returned to baseline by day 3 (382+/-318 RLU/mg of total lung protein); at day 5 no expression was detected, whereas gene expression under the Ubc promoter was detected up to day 40 (1989+/-710 RLU/mg of total lung protein) with a peak at day 20 (2821+/-2092 RLU/mg of total lung protein). Arterial blood gas (PaO2), histological assessment and cytokine measurements showed no significant toxicity neither at day 1 nor at day 40. CONCLUSIONS: These results provide evidence that in vivo electroporation is a safe and effective tool for non-viral gene delivery to the lungs. If this method is used in combination with a long-acting promoter system, sustained transgene expression can be achieved.

Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.