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.

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.

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.

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.

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.

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.

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.

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.

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 .

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.

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.

Effect of PEEP and I:E ratio on cerebral oxygenation in ARDS: an experimental study in anesthetized rabbit.

BACKGROUND: Although PEEP and inversed I:E ratio have been shown to improve gas exchange in ARDS, both can adversely affect systemic hemodynamics and cerebral perfusion. The goal of this study was to assess how changes in PEEP and I:E ratio affect systemic and cerebral oxygenation and perfusion in normal and injured lung. METHODS: Eight anesthetized Chinchilla-Bastard rabbits were ventilated at baseline with pressure-regulated volume control mode, VT = 6 ml/kg, PEEP = 6 cmH2O, FIO2 = 0.4; respiratory rate set for ETCO2 = 5.5%, and I:E = 1:2, 1:1 or 2:1 in random order. Ultrasonic carotid artery flow (CF), arterial (PaO2), jugular venous blood gases and near infrared spectroscopic cerebral oxygenation (∆HBO2) were recorded for each experimental condition. After induced lung injury, the animals were ventilated with PEEP = 9 followed by 6 cmH2O. RESULTS: At baseline, inverse-ratio ventilation (IRV) significantly reduced cerebral oxygenation (∆O2HB; - 27 at 1:2; - 15 at 1:1 vs. 0.27 µmol/L at 2:1; p < 0.05), due to a significant reduction in mean arterial pressure and CF without modifying gas exchange. In injured lung, IRV improved gas exchange but decreased cerebral perfusion without affecting brain oxygenation. The higher PEEP level, however, improved PaO2 (67.5 ± 19.3 vs. 42.2 ± 8.4, p < 0.05), resulting in an improved ∆HBO2 (- 13.8 ± 14.7 vs. -43.5 ± 21.3, p < 0.05), despite a drop in CF. CONCLUSIONS: Our data suggest that unlike moderate PEEP, IRV is not effective in improving brain oxygenation in ARDS. In normal lung, IRV had a deleterious effect on brain oxygenation, which is relevant in anesthetized patients.

Optimal crystalloid volume ratio for blood replacement for maintaining hemodynamic stability and lung function: an experimental randomized controlled study.

BACKGROUND: Crystalloids are first line in fluid resuscitation therapy, however there is a lack of evidence-based recommendations on the volume to be administered. Therefore, we aimed at comparing the systemic hemodynamic and respiratory effects of volume replacement therapy with a 1:1 ratio to the historical 1:3 ratio. METHODS: Anesthetized, ventilated rats randomly included in 3 groups: blood withdrawal and replacement with crystalloid in 1:1 ratio (Group 1, n = 11), traditional 1:3 ratio (Group 3, n = 12) and a control group with no interventions (Group C, n = 9). Arterial blood of 5% of the total blood volume was withdrawn 7 times, and replaced stepwise with different volume rations of Ringer's acetate, according to group assignments. Airway resistance (Raw), respiratory tissue damping (G) and tissue elastance (H), mean arterial pressure (MAP) and heart rate (HR) were assessed following each step of fluid replacement with a crystalloid (CR1-CR6). Lung edema index was measured from histological samples. RESULTS: Raw decreased in Groups 1 and 3 following CR3 (p < 0.02) without differences between the groups. H elevated in all groups (p < 0.02), with significantly higher changes in Group 3 compared to Groups C and 1 (both p = 0.03). No differences in MAP or HR were present between Groups 1 and 3. Lung edema was noted in Group 3 (p < 0.05). CONCLUSIONS: Fluid resuscitation therapy by administering a 1:1 blood replacement ratio revealed adequate compensation capacity and physiological homeostasis similar with no lung stiffening and pulmonary edema. Therefore, considering this ratio promotes the restrictive fluid administration in the presence of continuous and occult bleeding.

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits.

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (KATP) in vascular smooth muscle. Because airway smooth muscle also expresses KATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (group L), levosimendan after pretreatment with a KATP channel blocker (glibenclamide, group LG), glibenclamide only (group G), or solvent alone (dextrose, group C). Airway resistance (Raw), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in groups L and LG or glucose in groups G and C Sham treatments in groups C and G had no effect on lung responsiveness. However, levosimendan treatment in group L elevated CO and inhibited the MCh-induced airway responses [Raw changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 µg·kg-1·min-1 MCh, P < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, P < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a KATP-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.

Sevoflurane Relieves Lung Function Deterioration After Cardiopulmonary Bypass.

OBJECTIVE: To investigate sevoflurane's potential to alleviate the detrimental pulmonary changes after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized clinical investigation. SETTING: University hospital. PARTICIPANTS: One hundred ninety patients undergoing elective cardiac surgery. INTERVENTIONS: Ninety-nine patients under intravenous anesthesia were administered 1 minimal alveolar concentration of sevoflurane for 5 minutes after being weaned from CPB (group SEV); intravenous anesthesia was maintained in the other 91 patients (group CTRL). MEASUREMENTS AND MAIN RESULTS: Measurements were performed with open chest: before CPB, after CPB, and after intervention. The lungs' mechanical impedance and capnogram traces were recorded, arterial and central venous blood samples were analyzed, and lung compliance was documented. Airway resistance, tissue damping, and elastance were obtained from the impedance spectra. The capnogram phase III slope was determined using linear regression. The partial pressure of oxygen in the arterial blood/fraction of inspired oxygen ratio and shunt fraction were calculated from blood gas parameters. After CPB, sevoflurane induced bronchodilation, reflected in marked drops in airway resistance and smaller improvements in lung tissue viscoelasticity indicated by decreases in tissue damping and elastance. These changes were reflected in a decreased capnogram phase III slope and shunt fraction and increased partial pressure of oxygen in the arterial blood/fraction of inspired oxygen ratio and lung compliance. The more severe deteriorations that occurred after CPB, the greater improvements by sevoflurane were observed. CONCLUSIONS: Sevoflurane can alleviate CPB-induced bronchoconstriction, compromised lung tissue mechanics, and enhanced intrapulmonary shunt. This benefit has particular importance in patients with severe CPB-induced lung function deterioration.

Exposure to urban PM1 in rats: development of bronchial inflammation and airway hyperresponsiveness.

BACKGROUND: Several epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 µm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 µm and 2.5 µm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats. METHODS: Rats were either exposed for 6 weeks to 100 µg/m(3) (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed. RESULTS: No significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology. CONCLUSIONS: Our findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics.

BACKGROUND: Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB). METHODS: Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. RESULTS: Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and -0.57; P < 0.0001, respectively), whereas SIII correlated most strongly (P < 0.0001) with Raw (r = 0.63; P < 0.0001). CPB induced significant elevations in Raw and G and H (P < 0.0001). These adverse mechanical changes were reflected consistently in SII, SIII, and D2min, with weaker correlations with the dead-space indices (P < 0.0001). The intrapulmonary shunt expressed as the difference between the Enghoff and Bohr dead-space parameters was increased after CPB (95% ± 5% [SEM] vs 143% ± 6%; P < 0.001). CONCLUSIONS: In mechanically ventilated patients, the capnographic parameters from the early phase of expiration (SII and D2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.

Fluid replacement and respiratory function: comparison of whole blood with colloid and crystalloid: A randomised animal study.

BACKGROUND: Fluid replacement with blood products, colloids and crystalloids is associated with morbidity and mortality. Despite this, the consequences of fluid administration on airway and respiratory tissue properties are not fully understood. OBJECTIVE: Comparison of respiratory effects of fluid replacement with autologous blood (Group B), colloid (HES 6% 130/0.4, Group CO) or crystalloid solution (NaCl 0.9%, Group CR) after haemorrhage with separate assessments of airway resistance and respiratory tissue mechanics. DESIGN: A randomised study. SETTING: An experimental model of surgical haemorrhage and fluid replacement in rats. PARTICIPANTS: Anaesthetised, ventilated rats randomly allocated into three groups (Group B: n = 8, Group CO: n = 8, Group CR: n = 9). INTERVENTION: Animals were bled in six sequential steps, each manoeuvre targeting a loss of 5% of total blood volume. The blood loss was then replaced stepwise in a 1 : 1 ratio with one of the three fluids. MAIN OUTCOME MEASURE: After each step, airway resistance (Raw), tissue damping and elastance (H) were determined by forced oscillations. Oedema indices from lung weights and histology were also measured. RESULTS: Raw (mean ±â€ŠSD) decreased in all groups following blood loss (-20.3 ±â€Š9.5% vs. baseline, P < 0.05), and remained low following blood replacement (-21.7 ±â€Š14.5% vs. baseline, P < 0.05), but was normalised by colloid (5.5 ±â€Š10.7%, NS). Crystalloid administration exhibited an intermediate reversal effect (-8.4 ±â€Š14.7%, NS). Tissue viscoelasticity increased following both blood loss and replacement, with no evidence of a significant difference in H between Groups CO and CR. More severe oedema was observed in Groups CR and CO than in Group B (P < 0.05), with no difference between the colloid and crystalloid solutions. CONCLUSION: This model, which mimics surgical haemorrhage, yields no evidence of a difference between colloids and crystalloids with regard to the pulmonary consequences of blood volume restoration. Functional changes in the lung should not be a key concern when choosing fluid replacement therapy with these solutions.

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.