Individual benefit in heart sparing during DIBH-supported left breast radiotherapy.

Introduction: Deep-inspirational breath hold (DIBH) is an option for heart protection in breast radiotherapy; we intended to study its individual benefit. Materials and Methods: 3DCRT treatment planning was performed in a cohort of 103 patients receiving radiotherapy of the whole breast (WBI)/chest wall (CWI) ± nodal regions (NI) both under DIBH and free breathing (FB) in the supine position, and in the WBI only cases prone (n = 45) position, too. A series of patient-related and heart dosimetry parameters were analyzed. Results: The DIBH technique provided dramatic reduction of all heart dosimetry parameters the individual benefit, however, varied. In the whole population the best predictor of benefit was the ratio of ipsilateral lung volume (ILV)FB and ILVDIBH. In the WBI cohort 9-11 patients and 5-8 patients received less dose to selected heart structures with the DIBH and prone positioning, respectively; based on meeting various dose constraints DIBH was the only solution in 6-13 cases, and prone positioning in 5-6 cases. In addition to other excellent predictors, a small ILVFB or ILVDIBH with outstanding predicting performance (AUC ≥ 0.90) suggested prone positioning. Detailed analysis consistently indicated the outstanding performance of ILVFB and ILVDIBH in predicting the benefit of one over the other technique in lowering the mean heart dose (MHD), left anterior descending coronary artery (LAD) mean dose and left ventricle(LV)-V5Gy. The preference of prone positioning was further confirmed by anatomical parameters measured on a single CT scan at the middle of the heart. Performing spirometry in a cohort of 12 patients, vital capacity showed the strongest correlation with ILVFB and ILVDIBH hence this test could be evaluated as a clinical tool for patient selection. Discussion: Individual lung volume measures estimated by spirometry and anatomical data examined prior to acquiring planning CT may support the preference of DIBH or prone radiotherapy for optimal heart protection.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Comparison of the respiratory effects of commonly utilized general anaesthesia regimes in male Sprague-Dawley rats.

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared. Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6 cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness. Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p < 0.001), no between-group differences were observed (p > 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups. Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.

Benefit of Flow-Controlled Over Pressure-Regulated Volume Control Mode During One-Lung Ventilation: A Randomized Experimental Crossover Study.

BACKGROUND: Application of a ventilation modality that ensures adequate gas exchange during one-lung ventilation (OLV) without inducing lung injury is of paramount importance. Due to its beneficial effects on respiratory mechanics and gas exchange, flow-controlled ventilation (FCV) may be considered as a protective alternative mode of traditional pressure- or volume-controlled ventilation during OLV. We investigated whether this new modality provides benefits compared with conventional ventilation modality for OLV. METHODS: Ten pigs were anaesthetized and randomly assigned in a crossover design to be ventilated with FCV or pressure-regulated volume control (PRVC) ventilation. Arterial partial pressure of oxygen (Pa o2 ), carbon dioxide (Pa co2 ), ventilation and hemodynamical parameters, and lung aeration measured by electrical impedance tomography were assessed at baseline and 1 hour after the application of each modality during OLV using an endobronchial blocker. RESULTS: Compared to PRVC, FCV resulted in increased Pa o2 (153.7 ± 12.7 vs 169.9 ± 15.0 mm Hg; P = .002) and decreased Pa co2 (53.0 ± 11.0 vs 43.2 ± 6.0 mm Hg; P < .001) during OLV, with lower respiratory elastance (103.7 ± 9.5 vs 77.2 ± 10.5 cm H 2 O/L; P < .001) and peak inspiratory pressure values (27.4 ± 1.9 vs 22.0 ± 2.3 cm H 2 O; P < .001). No differences in lung aeration or hemodynamics could be detected between the 2 ventilation modalities. CONCLUSIONS: The application of FCV in OLV led to improvement in gas exchange and respiratory elastance with lower ventilatory pressures. Our findings suggest that FCV may offer an optimal, protective ventilation modality for OLV.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Background: Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. Methods: In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. Results: The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Conclusion: Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. Trial registration: NCT05812196.

Expiratory high-frequency percussive ventilation: a novel concept for improving gas exchange.

BACKGROUND: Although high-frequency percussive ventilation (HFPV) improves gas exchange, concerns remain about tissue overdistension caused by the oscillations and consequent lung damage. We compared a modified percussive ventilation modality created by superimposing high-frequency oscillations to the conventional ventilation waveform during expiration only (eHFPV) with conventional mechanical ventilation (CMV) and standard HFPV. METHODS: Hypoxia and hypercapnia were induced by decreasing the frequency of CMV in New Zealand White rabbits (n = 10). Following steady-state CMV periods, percussive modalities with oscillations randomly introduced to the entire breathing cycle (HFPV) or to the expiratory phase alone (eHFPV) with varying amplitudes (2 or 4 cmH2O) and frequencies were used (5 or 10 Hz). The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined. Volumetric capnography was used to evaluate the ventilation dead space fraction, phase 2 slope, and minute elimination of CO2. Respiratory mechanics were characterized by forced oscillations. RESULTS: The use of eHFPV with 5 Hz superimposed oscillation frequency and an amplitude of 4 cmH2O enhanced gas exchange similar to those observed after HFPV. These improvements in PaO2 (47.3 ± 5.5 vs. 58.6 ± 7.2 mmHg) and PaCO2 (54.7 ± 2.3 vs. 50.1 ± 2.9 mmHg) were associated with lower ventilation dead space and capnogram phase 2 slope, as well as enhanced minute CO2 elimination without altering respiratory mechanics. CONCLUSIONS: These findings demonstrated improved gas exchange using eHFPV as a novel mechanical ventilation modality that combines the benefits of conventional and small-amplitude high-frequency oscillatory ventilation, owing to improved longitudinal gas transport rather than increased lung surface area available for gas exchange.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar-capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes.

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange.

OBJECTIVE: To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. DESIGN: A prospective, nonrandomized clinical investigation. SETTING: A university hospital. PARTICIPANTS: One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. INTERVENTIONS: Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. MEASUREMENTS AND MAIN RESULTS: Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. CONCLUSION: Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Size of the Carotid Body in Patients with Cardiovascular and Respiratory Diseases Measured by Computed Tomography Angiography: A Case-Control Study.

OBJECTIVES: Carotid bodies (CBs) play an important role in regulating sympathetic nervous system activity. Thus, they are likely to be enlarged in patients with certain cardiovascular and respiratory diseases. The aim of this case-control study was to verify this hypothesis using computed tomography angiography (CTA). METHODS: We retrospectively analysed 141 CTAs including 16 controls, 96 patients with only hypertension (HT), 12 with HT and previous acute myocardial infarction (AMI), 9 with HT and heart failure (HF), and 8 with HT and chronic obstructive pulmonary disease (COPD). We assessed the data using analysis of variance, with p < 0.05 indicating significance. RESULTS: CB average areas in the controls were 2.31 mm2 (right side (RS)) vs. 2.34 mm2 (left side (LS)). CB size was significantly enlarged in patients with HT: 3.07 mm2 (RS) (p=0.019) vs. 2.91 mm2 (LS) (p=0.002). If AMI (RS: 3.5 mm2; LS: 3.44 mm2) or HF (RS: 4.01 mm2; LS: 4.55 mm2) was associated with HT, the CB size was even more enlarged. COPD did not affect CB size (RS: 2.40 mm2; LS: 2.29 mm2). CONCLUSIONS: Our data showed that certain diseases with increased activity of the sympathetic nervous system were associated with significantly enlarged CBs.

Effect of Permissive Mild Hypercapnia on Cerebral Vasoreactivity in Infants: A Randomized Controlled Crossover Trial.

BACKGROUND: Mechanical ventilation interferes with cerebral perfusion via changes in intrathoracic pressure and/or as a consequence of alterations in CO2. Cerebral vascular vasoreactivity is dependent on CO2, and hypocapnia can potentially lead to vasoconstriction and subsequent decrease in cerebral blood flow. Thus, we aimed at characterizing whether protective ventilation with mild permissive hypercapnia improves cerebral perfusion in infants. METHODS: Following ethical approval and parental consent, 19 infants were included in this crossover study and randomly assigned to 2 groups for which the initial ventilation parameters were set to achieve an end-tidal carbon dioxide (Etco2) of 6.5 kPa (group H: mild hypercapnia, n = 8) or 5.5 kPa (group N: normocapnia, n = 11). The threshold was then reversed before going back to the initial set value of normo- or hypercapnia. At each step, hemodynamic, respiratory, and near-infrared spectroscopy (NIRS)-derived parameters, including tissue oxygenation index (TOI) and tissue hemoglobin index (THI), concentration of deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb), were collected. Concomitantly, sevoflurane maintenance concentration, ventilatory (driving pressure) and hemodynamic parameters, as mean arterial pressure (MAP), were recorded. RESULTS: Targeting an Etco2 of 5.5 kPa resulted in significantly higher mean driving pressure than an Etco2 of 6.5 kPa (P < .01) with no difference between the groups in end-tidal sevoflurane, MAP, and heart rate. A large scatter was observed in NIRS-derived parameters, with no evidence for difference in Etco2 changes between or within groups. A mild decrease with time was observed in THI and MAP in infants randomly assigned to group N (P < .036 and P < .017, respectively). When pooling all groups together, a significant correlation was found between the changes in MAP and TOI (r = 0.481, P < .001). CONCLUSIONS: Allowing permissive mild hypercapnia during mechanical ventilation of infants led to lower driving pressure and comparable hemodynamic, respiratory, and cerebral oxygenation parameters than during normocapnia. Whereas a large scatter in NIRS-derived parameters was observed at all levels of Etco2, the correlation between TOI and MAP suggests that arterial pressure is an important component of cerebral oxygenation at mild hypercapnia.

Use of capnography to verify emergency ventilator sharing in the COVID-19 era.

Exacerbation of COVID-19 pandemic may lead to acute shortage of ventilators, which may require shared use of ventilator as a lifesaving concept. Two model lungs were ventilated with one ventilator to i) test the adequacy of individual tidal volumes via capnography, ii) assess cross-breathing between lungs, and iii) offer a simulation-based algorithm for ensuring equal tidal volumes. Ventilation asymmetry was induced by placing rubber band around one model lung, and the uneven distribution of tidal volumes (VT) was counterbalanced by elevating airflow resistance (HR) contralaterally. VT, end-tidal CO2 concentration (ETCO2), and peak inspiratory pressure (Ppi) were measured. Unilateral LC reduced VT and elevated ETCO2 on the affected side. Under HR, VT and ETCO2 were re-equilibrated. In conclusion, capnography serves as simple, bedside method for controlling the adequacy of split ventilation in each patient. No collateral gas flow was observed between the two lungs with different time constants. Ventilator sharing may play a role in emergency situations.

Obesity and diabetes: similar respiratory mechanical but different gas exchange defects.

Diabetes mellitus increases smooth muscle tone and causes tissue remodeling, affecting elastin and collagen. Although the lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body shapes were divided into the control nondiabetic (n = 73) and diabetic (n = 31) groups. The other two groups included obese patients without diabetes (n = 43) or with diabetes (n = 30). The mechanical properties of the respiratory system were determined by forced oscillation technique. Airway resistance (Raw), tissue damping (G), and tissue elastance (H) were assessed by forced oscillation. Capnography was applied to determine phase 3 slopes and dead space indices. The intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FIO2) were estimated from arterial and central venous blood samples. Compared with the corresponding control groups, diabetes alone increased the Raw (7.6 ± 6 cmH2O.s/l vs. 3.1 ± 1.9 cmH2O.s/l), G (11.7 ± 5.5 cmH2O/l vs. 6.5 ± 2.8 cmH2O/l), and H (31.5 ± 11.8 cmH2O/l vs. 24.2 ± 7.2 cmH2O/l (P < 0.001 for all). Diabetes increased the capnographic phase 3 slope, whereas PaO2/FIO2 or Qs/Qt was not affected. Obesity alone caused similar detrimental changes in respiratory mechanics and alveolar heterogeneity, but these alterations also compromised gas exchange. We conclude that diabetes-induced intrinsic mechanical abnormalities are counterbalanced by hypoxic pulmonary vasoconstriction, which maintained intrapulmonary shunt fraction and oxygenation ability of the lungs.

Physiologically variable ventilation reduces regional lung inflammation in a pediatric model of acute respiratory distress syndrome.

BACKGROUND: Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS). METHODS: New-Zealand White rabbit pups (n = 36, 670 ± 20 g [half-width 95% confidence interval]), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly. RESULTS: Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p < 0.04), however, this trend was improved by PVV (1 ± 4%, - 6 ± 2%). Animals receiving PVV presented reduced inflammation as assessed by lung normalized [18F]fluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p < 0.05), particularly in the well and poorly aerated lung zones. No benefit of PVV could be detected on regional blood perfusion or blood gas parameters. CONCLUSIONS: Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.

Determination of adequate positive end-expiratory pressure level required for carbon dioxide homeostasis in an animal model of infant laparoscopy.

BACKGROUND: Capnoperitoneum provides a ventilatory challenge due to reduction in end-expiratory lung volume and peritoneal carbon dioxide absorption in both children and adults. The primary aim of this controlled interventional trial was to determine the positive end-expiratory pressure (PEEP) level needed to ensure for adequate carbon dioxide clearance and preservation of carbon dioxide homeostasis in an experimental model of infant laparoscopy. The secondary aim was to evaluate potential effects on cardiac output of PEEP and abdominal pressure level variations in the same setting. METHODS: Eight chinchilla bastard rabbits were anesthetized and mechanically ventilated. Intra-abdominal pressures were randomly set to 0, 6, and 12 mm Hg by carbon dioxide insufflation. Carbon dioxide clearance using volumetric capnography, arterial blood gas data, and cardiac output was recorded, while PEEP 3, 6, and 9 cmH2 O were applied in a random order. RESULTS: A PEEP of 9 cmH2 O showed restoration of carbon dioxide clearance without causing changes in arterial partial pressure of carbon dioxide and bicarbonate and with no associated deterioration in cardiac output. CONCLUSION: The results promote a PEEP level of 9 cmH2 O in this model of infant capnoperitoneum to allow for adequate carbon dioxide removal with subsequent preservation of carbon dioxide homeostasis. The use of high PEEP was not associated with any decrease in cardiac output.

End-expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum.

BACKGROUND: Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELV CO 2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS: Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELV CO 2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS: Significant correlations were found between EELV CO 2 and EELVHe before capnoperitoneum (r = .85, P < .001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between EELV CO 2 and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20 mL kg-1 , determined with a receiver operating characteristic curve, was associated with near-normal LCI values. CONCLUSION: In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on EELV CO 2 requires an open lung strategy, defined as EELV above approximately 20 mL kg-1 .

Lung volume dependence of respiratory function in rodent models of diabetes mellitus.

BACKGROUND: Diabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters. METHODS: Rats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology. RESULTS: The rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained. CONCLUSIONS: These findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.

Reversing Cholinergic Bronchoconstriction by Common Inotropic Agents: A Randomized Experimental Trial on Isolated Perfused Rat Lungs.

BACKGROUND: The ability of inotropic agents to alter airway reactivity and lung tissue mechanics has not been compared in a well-controlled experimental model. Therefore, we compared the potential to alter lung tissue viscoelasticity and bronchodilator effects of commonly used inotropic agents in an isolated perfused rat lung model. METHODS: After achieving steady state lung perfusion, sustained bronchoconstriction was induced by acetylcholine (ACh). Isolated rat lungs were then randomly allocated to 6 groups treated with either saline vehicle (n = 8) or incremental concentrations of inotropes (adrenaline, n = 8; dopamine, n = 7; dobutamine, n = 7; milrinone, n = 8; or levosimendan, n = 6) added to the whole-blood perfusate. Airway resistance (Raw), lung tissue damping (G), and elastance were measured under baseline conditions, during steady-state ACh-induced constriction and for each inotrope dose. RESULTS: No change in Raw was observed after addition of the saline vehicle. Raw was significantly lower after addition of dopamine (maximum difference [95% CI] of 29 [12-46]% relative to the saline control, P = .004), levosimendan (58 [39-77]%, P < .001), and adrenaline (37 [21-53]%, P < .001), whereas no significant differences were observed at any dose of milrinone (5 [-12 to 22]%) and dobutamine (4 [-13 to 21]%). Lung tissue damping (G) was lower in animals receiving the highest doses of adrenaline (difference: 22 [7-37]%, P = .015), dobutamine (20 [5-35]%, P = .024), milrinone (20 [6-34]%, P = .026), and levosimendan (36 [19-53]%, P < .001) than in controls. CONCLUSIONS: Although dobutamine and milrinone did not reduce cholinergic bronchoconstriction, they reversed the ACh-induced elevations in lung tissue resistance. In contrast, adrenaline, dopamine, and levosimendan exhibited both potent bronchodilatory action against ACh and diminished lung tissue damping. Further work is needed to determine whether these effects are clinically relevant in humans.

Variable Ventilation Is Equally Effective as Conventional Pressure Control Ventilation for Optimizing Lung Function in a Rabbit Model of ARDS.

BACKGROUND: Introducing mathematically derived variability (MVV) into the otherwise monotonous conventional mechanical ventilation has been suggested to improve lung recruitment and gas exchange. Although the application of a ventilation pattern based on variations in physiological breathing (PVV) is beneficial for healthy lungs, its value in the presence of acute respiratory distress syndrome (ARDS) has not been characterized. We therefore aimed at comparing conventional pressure-controlled ventilation with (PCS) or without regular sighs (PCV) to MVV and PVV at two levels of positive end-expiratory pressure (PEEP) in a model of severe ARDS. METHODS: Anesthetised rabbits (n = 54) were mechanically ventilated and severe ARDS (PaO2/FiO2 ≤ 150 mmHg) was induced by combining whole lung lavage, i.v. endotoxin and injurious ventilation. Rabbits were then randomly assigned to be ventilated with PVV, MVV, PCV, or PCS for 5 h while maintaining either 6 or 9 cmH2O PEEP. Ventilation parameters, blood gas indices and respiratory mechanics (tissue damping, G, and elastance, H) were recorded hourly. Serum cytokine levels were assessed with ELISA and lung histology was analyzed. RESULTS: Although no progression of lung injury was observed after 5 h of ventilation at PEEP 6 cmH2O with PVV and PCV, values for G (58.8 ± 71.1[half-width of 95% CI]% and 40.8 ± 39.0%, respectively), H (54.5 ± 57.2%, 50.7 ± 28.3%), partial pressure of carbon-dioxide (PaCO2, 43.9 ± 23.8%, 46.2 ± 35.4%) and pH (-4.6 ± 3.3%, -4.6 ± 2.2%) worsened with PCS and MVV. Regardless of ventilation pattern, application of a higher PEEP improved lung function and precluded progression of lung injury and inflammation. Histology lung injury scores were elevated in all groups with no difference between groups at either PEEP level. CONCLUSION: At moderate PEEP, variable ventilation based on a pre-recorded physiological breathing pattern protected against progression of lung injury equally to the conventional pressure-controlled mode, whereas mathematical variability or application of regular sighs caused worsening in lung mechanics. This outcome may be related to the excessive increases in peak inspiratory pressure with the latter ventilation modes. However, a greater benefit on respiratory mechanics and gas exchange could be obtained by elevating PEEP, compared to the ventilation mode in severe ARDS.