Thammanomai et al.(99 Thammanomai A, Hueser LE, Majumdar A, Bartolák-Suki E, Suki B. Design of a new variable-ventilation method optimized for lung recruitment in mice. J Appl Physiol (1995). 2008;104(5):1329-40.)
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G1, G2, G3, and G4 = 8 animals in each group with ARDS and 8 animals without ARDS |
Mice (22 - 26g) with and without ARDS ventilated for 60 minutes |
To investigate the physiological effects of VV and test the hypothesis that the beneficial effects of VV are due to the variability in TV considering its distribution and not simply the presence of large ventilation volumes |
G1: CV (TV of 8mL/kg; RR of 240rpm; PEEP of 3cmH2O) G2: Original VV (variable RR and TV to maintain the Vmin of CV) G3: CV with sighs (large breaths, two ventilations per minute) G4: New VV (variable RR and TV - minimum, peak, and maximum volumes - to keep the same Vmin) |
The new VV and CV with sighs led to stable dynamic equilibrium in alveolar recruitment that significantly outperformed the CV and the original VV. During the new VV, this balance improved pulmonary mechanics |
Berry et al.(1010 Berry CA, Suki B, Polglase GR, Pillow JJ. Variable ventilation enhances ventilation without exacerbating injury in preterm lambs with respiratory distress syndrome. Pediatr Res. 2012;72(4):384-92.)
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G1 = 6 animals G2 = 8 animals G3 = 8 animals |
Premature lambs (3.2 kg) with 129 days of gestation, ventilated for 3 hours |
To assess whether VV is effective for achieving permissive hypercapnia without increasing injury markers or pulmonary inflammation compared with CV |
G1: CG (without the use of MV) G2: CV (TV to achieve a PaCO2 of 40 - 50mmHg) G3: VV (variable TV and RR to maintain the Vmin of CV) |
VV promoted recruitment and increased ventilatory efficiency without increasing pulmonary inflammation or injury |
Bellardine et al.(1111 Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, et al. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med. 2006;34(2):439-45.)
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G1 = 6 animals G2 = 7 animals |
Sheep (59.8 ± 10.5kg) with ARDS ventilated for 4 hours |
To compare VV with CV in terms of gas exchange, hemodynamics, and lung mechanics |
G1: CV (TV of 10mL/kg; RR of 16bpm; PEEP of 7.5cmH2O; FiO2 of 1.0) G2: VV (variable RR and TV to maintain the Vmin of CV; PEEP of 7.5cmH2O; FiO2 of 1.0) |
VV provided continuous improvement in oxygenation and ventilation pressures and overall better pulmonary mechanics while minimizing pulmonary damage |
Mutch et al.(1212 Mutch WA, Eschun GM, Kowalski SE, Graham MR, Girling LG, Lefevre GR. Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth. 2000;84(2):197-203.)
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G1 = 10 animals G2 = 10 animals |
Pigs (20 - 30kg) ventilated for 7 hours |
To compare gas exchange and respiratory mechanics in CV and VV during prolonged anesthesia |
G1: CV (RR of 15rpm; Vmin adjusted to deliver a TV of approximately 10mL/kg) G2: VV (variable TV and RR to maintain the Vmin of CV) |
Deterioration of gas exchange and respiratory mechanics occurred with CV but not in VV |
Mutch et al.(1313 Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000;28(7):2457-64.)
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G1 = 9 animals G2 = 8 animals |
Pigs (20 - 30kg) with ARDS ventilated for 4 hours |
To assess whether VV had positive effects when used with PEEP |
G1: CV (RR of 15rpm; PEEP of 10cmH2O) G2: VV (variable RR with reciprocal changes of TV; PEEP of 10cmH2O) |
VV with PEEP of 10cmH2O improved arterial oxygenation compared with CV with the same PEEP value |
Arold et al.(1414 Arold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med. 2002;165(3):366-71.)
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G1 = 4 animals G2 = 10 animals |
Guinea pigs (500 - 600g) with ARDS ventilated for 3 hours |
To test whether the ability of VV to improve oxygenation and pulmonary mechanics depends on the amount of variability added to TV |
G1: CV (RR of 60bpm; TV of 5.1mL/kg, PEEP of 3cmH2O) G2: VV (different variations of VT - 10%, 20%, 40%, and 60% of the average - adjustment of RR to maintain the Vmin of CV) |
VV was effective in improving lung function and gas exchange in an ARDS model |
Boker et al.(1515 Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, et al. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002;165(4):456-62.)
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G1 = 8 animals G2 = 9 animals |
Pigs with ARDS mechanically ventilated for 5 hours |
To measure changes in PaO2, lung compliance, and proinflammatory cytokines in MV with and without biological variability using an ARDSnet protocol(1616 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.)
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G1: CV (RR of 30bpm; TV of 6mL/kg) G2: VV (variable RR and TV in the same average) |
The variability added to the ARDSnet protocol improved oxygenation and reduced the shunting fraction, peak airway pressure, and IL-8 concentrations in the tracheal aspirate |
Arold et al.(1717 Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003;285(2):L370-5.)
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G1 = 6 animals G2 = 5 animals G3 = 5 animals |
Guinea pigs (500 - 600g) ventilated for 3 hours |
To test whether VV promoted the release of surfactant in vivo |
G1: CV (RR of 60rpm; TV of 5mL/kg, PEEP of 3cmH2O) G2: VV (variable RR and TV to maintain the Vmin of CV) G3: CG (Without the use of MV) |
VV promoted the release of surfactant, reduced lung damage, and improved blood oxygenation |
Funk et al.(1818 Funk DJ, Graham MR, Girling LG, Thliveris JA, McManus BM, Walker EK, et al. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury. Respir Res. 2004;5:22.)
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G1 = 8 animals G2 = 8 animals G3 = 8 animals |
Pigs (20 - 30kg) with ARDS ventilated for 5 hours |
To compare three ventilation strategies in terms of gas exchange, respiratory mechanics, inflammatory levels, and surfactant function |
G1: CV (TV of 7mL/kg; RR of 30bpm; PEEP of 10cmH2O) G2: CV with ARM (40cmH2O for 40 seconds every hour) G3: VV (variable TV; RR of 30bpm; PEEP of 10cmH2O) |
VV with a human variability file was greater than CV, and CV with ARM was used for the sustained improvement of gas exchange and respiratory mechanics |
Mutch et al.(1919 Mutch WA, Graham MR, Girling LG, Brewster JF. Fractal ventilation enhances respiratory sinus arrhythmia. Respir Res. 2005;6:41.)
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10 animals |
Pigs (30 - 40kg) initially with healthy lungs and then with ARDS |
To test whether the imposition of a variable respiratory signal with the addition of physiological noise affected cardiorespiratory oscillators |
The animals were subjected to MV for 4 to 5 minutes for each ventilation mode - CV and VV (variable RR and TV to maintain the Vmin of CV) - before and after ARDS |
The increase of respiratory sinus arrhythmia by VV may be used to improve the recoupling of organic systems |
McMullen et al.(2020 McMullen MC, Girling LG, Graham MR, Mutch WA. Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology. 2006;105(1):91-7.)
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G1 = 8 animals G2 = 8 animals |
Pigs (25 - 30kg) subjected to selective MV in the dependent lung for 90 minutes and for another 60 minutes after the restoration of ventilation in both lungs |
To compare VV with CV in terms of gas exchange and pulmonary mechanics during selective ventilation and after ARM and the reestablishment of ventilation in both lungs |
G1: CV (TV of 12mL/kg; RR of 20rpm; PEEP of 5cmH2O) G2: VV (algorithm of variability of RR and TV to ensure the Vmin of CV) |
In the selective ventilation model, VV improved gas exchange and respiratory mechanics compared with CV. A better static compliance in VV persisted with the restoration of ventilation in both lungs |
Mutch et al.(2121 Mutch WA, Buchman TG, Girling LG, Walker EK, McManus BM, Graham MR. Biologically variable ventilation improves gas exchange and respiratory mechanics in a model of severe bronchospasm. Crit Care Med. 2007;35(7):1749-55.)
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G1 = 9 animals G2 = 9 animals |
Pigs (25 - 30kg) with bronchospasm ventilated for 4 hours |
To compare VV with CV in terms of gas exchange, respiratory mechanics, CO2 exhalation, and inflammatory cytokines in the bronchoalveolar lavage fluid |
G1: CV (TV of 10mL/kg) G2: VV (variable RR and TV to maintain a constant Vmin) |
VV performed better than CV in terms of gas exchange and respiratory mechanics during severe bronchospasm but without significant differences regarding inflammatory cytokines |
Spieth et al.(2222 Spieth PM, Carvalho AR, Pelosi P, Hoehn C, Meissner C, Kasper M, et al. Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury. Am J Respir Crit Care Med. 2009;179(8):684-93.)
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G1 = 9 animals G2 = 9 animals G3 = 9 animals G4 = 9 animals |
Pigs (23.8 - 37kg) with ARDS ventilated for 6 hours |
To determine the impact of VV on pulmonary function and its effect on pulmonary parenchyma compared with conventional protective MV strategies |
G1: CV - ARDSnet(1616 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.) G2: VV - ARDSnet(1616 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-8.) (variable TV) G3: CV - OLA(2323 Amato MB, Barbas CS, Medeiros DM, Schettino GP, Lorenzi Filho G, Kairalla RA, et al. Beneficial effects of the ''open lung approach'' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1835-46.) G4: VV - OLA(2323 Amato MB, Barbas CS, Medeiros DM, Schettino GP, Lorenzi Filho G, Kairalla RA, et al. Beneficial effects of the ''open lung approach'' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1835-46.) (variable TV) |
The use of variable TV improved respiratory function and reduced histologic damage during MV according to ARDSnet and OLA protocols without increasing pulmonary inflammation and mechanical stress |
Spieth et al.(2424 Spieth PM, Carvalho AR, Güldner A, Kasper M, Schubert R, Carvalho NC, et al. Pressure support improves oxygenation and lung protection compared to pressure-controlled ventilation and is further improved by random variation of pressure support. Crit Care Med. 2011;39(4):746-55.)
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G1 = 8 animals G2 = 8 animals G3 = 8 animals |
Pigs (27.2 - 37kg) with ARDS ventilated for 6 hours |
To test whether PAV and variable PSV improved oxygenation and reduced the lung damage associated with MV compared with PCV and whether variable PSV further improved oxygenation and reduced lung lesions compared with conventional PSV |
G1: CV - (PCV; RR to achieve a pH > 7.25; TV of approximately 6mL/kg, PEEP of 8cmH2O) G2: CV - (PSV - free RR, TV of approximately 6mL/kg, PEEP of 8cmH2O) G3: VV - (variable PSV - support pressure with a variation of 30% to achieve a TV of approximately 6mL/kg) |
PSV and variable PSV reduced lung injury and inflammation and improved gas exchange in relation to protective PCV. Variable PSV further improved oxygenation and reduced inspiratory effort with less alveolar edema and inflammatory infiltration compared to conventional PSV |
Ruth Graham et al.(2525 Ruth Graham M, Goertzen AL, Girling LG, Friedman T, Pauls RJ, Dickson T, et al. Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement. Crit Care Med. 2011;39(7):1721-30.)
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G1 = 6 animals G2 = 8 animals G3 = 6 animals G4 = 8 animals |
Pigs (10 - 15kg) with ARDS ventilated for 4 hours |
To test whether aeration, gas exchange, and pulmonary mechanics were improved when administration of the surfactant was combined with VV |
G1: CV (RR of 30rpm; TV of 7.5mL/kg, PEEP of 10cmH2O) G2: CV with surfactant replacement G3: VV (variable RR and TV) G4: VV with surfactant replacement |
Isolated VV was more effective in reestablishing gas exchange and pulmonary mechanics and had a positive effect on lung recruitment |
Graham et al.(2626 Graham MR, Gulati H, Kha L, Girling LG, Goertzen A, Mutch WA. Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury. Can J Anesth. 2011;58(8):740-50.)
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G1 = 8 animals G2 = 8 animals |
Pigs (22 - 30kg) with ARDS ventilated for 4 hours |
To test whether alveolar recruitment and periodic breathing with low TV, as observed with VV, increased the resolution of edema in ARDS |
G1: CV (TV < 7.5mL/kg, PEEP of 10cmH2O; fixed Vmin) G2: VV (variable RR with reciprocal changes in TV to maintain a Vmin; PEEP of 10cmH2O) |
The CT suggested that the beneficial redistribution and enhanced clearance of pulmonary edema contributed to the beneficial effects of VV |
Pillow et al.(2727 Pillow JJ, Musk GC, McLean CM, Polglase GR, Dalton RG, Jobe AH, et al. Variable ventilation improves ventilation and lung compliance in preterm lambs. Intensive Care Med. 2011;37(8):1352-9.)
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G1 = 7 animals G2 = 9 animals G3 = 9 animals |
Premature lambs with 129 days of gestation ventilated for 2 hours |
To test whether VV improved arterial oxygenation, ventilatory efficiency, and lung compliance |
G1: CV (PRVC - TV of 11mL/kg; RR of 50rpm; maximum peak inspiratory pressure of 40cmH2O) G2: VV (variable TV and RR to maintain the Vmin of CV) G3: CG (without the use of MV) |
VV improved lung compliance and ventilatory efficiency compared with CV |
Carvalho et al.(2828 Carvalho AR, Spieth PM, Güldner A, Cuevas M, Carvalho NC, Beda A, et al. Distribution of regional lung aeration and perfusion during conventional and noisy pressure support ventilation in experimental lung injury. J Appl Physiol (1985). 2011;110(4):1083-92.)
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12 animals |
Pigs (33.1 - 46.6Kg) with ARDS ventilated for 1 hour in each mode |
To evaluate the effect of PSV and variable PSV compared to PCV in the regional distribution of aeration, reaeration, and current hyperinflation, and the distribution of ventilation and pulmonary blood flow |
CV - (PCV - TV ≈ 6mL/kg; RR to maintain pH > 7.3; PEEP of 8cmH2O) CV - (PSV - TV ≈ 6mL/kg; free RR; PEEP of 8cmH2O) VV - (variable PSV - support pressure with 20% variation to achieve a TV of ≈ 6mL/kg) |
PSV and variable PSV improved oxygenation and intrapulmonary shunting compared with PCV. Compared with PSV, variable PSV redistributed the perfusion of caudal to cranial zones, further improving oxygenation |
Spieth et al.(2929 Spieth PM, Güldner A, Beda A, Carvalho N, Nowack T, Krause A, et al. Comparative effects of proportional assist and variable pressure support ventilation on lung function and damage in experimental lung injury. Crit Care Med. 2012;40(9):2654-61.)
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G1 = 8 animals G2 = 8 animals G3 = 8 animals |
Pigs (26.8 - 34.4kg) with ARDS ventilated for 6 hours |
To determine the effect of PAV, variable PSV, and conventional PSV on lung function, respiratory pattern, and lung damage |
G1: CV - (PAV - assisted flux of 60%; assisted TV adjusted to achieve a target TV of ≈ 6mL/kg) G2: CV - (PSV - support pressure configured to reach a TV of ≈ 6mLkg) G3: VV - (variable PSV - support pressure with a variation of 30% to achieve a TV of approximately 6mL/kg) |
PAV and variable PSV increased the variability of TV and improved the oxygenation and venous mixture without affecting the patient-ventilator synchrony or lung injury compared with conventional PSV. PSV and variable PSV reduced the inspiratory effort compared with PAV |
Thammanomai et al.(3030 Thammanomai A, Hamakawa H, Bartolák-Suki E, Suki B. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury. PLoS One. 2013;8(1):e53934.)
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G1 = 8 animals G2 = 8 animals G3 = 8 animals G4 = 8 animals |
Rats (22 - 26g) with ARDS |
To investigate the combined effects of ventilation modes and PEEP on pulmonary mechanics, gas exchange, and lung biology, including surfactant and epithelial cell integrity, at two PEEP levels |
G1: CV (TV of 8mL/kg; RR of 240rpm) with PEEP of 3 and 6cmH2O. G2: CV with sighs (large ventilations, two every minute) with PEEP of 3 and 6cmH2O G3: New VV (variable RR and TV - minimum, peak, and maximum volumes - to maintain the Vmin of CV) with PEEP of 3 and 6cmH2O G4: CG (received only the initial ventilation after lung injury) with PEEP of 3 and 6cmH2O |
PEEP had a significant effect on the performance of all the ventilation modes. The higher PEEP protected the lung from collapse and reduced tissue heterogeneity. However, the lower PEEP better protected the epithelium and had a positive effect on the surfactant, particularly during VV |
Samary et al.(311 Ivanov PC, Amaral LA, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, et al. Multifractality in human heartbeat dynamics. Nature. 1999;399(6735):461-5.)
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G1 = 12 animals G2 = 12 animals |
Wistar rats (365 ± 55g) with pulmonary and extrapulmonary ARDS ventilated for 1 hour |
To compare VV with CV |
G1: CV (VCV - TV 6mL/kg, PEEP of 5cmH2O) G2: VV (VCV - variable TV, coefficient of variation of 30%; PEEP of 5cmH2O) |
VV improved lung function in both groups. However, VV had further beneficial effects on biological markers in pulmonary ARDS than in extrapulmonary ARDS |