Multicenter Comparative Study of Conventional Mechanical Gas Ventilation to Tidal Liquid Ventilation in Oleic Acid Injured Sheep

Abstract

We performed a multicenter study to test the hypothesis that tidal liquid ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p < 0.01) during TLV than CMV: PaO2, venous oxygen saturation, respiratory compliance, cardiac output, stroke volume, oxygen delivery, ventilatory efficiency index; alveolar area, lung % gas exchange space, and expansion index. The following were lower (p < 0.01) during TLV compared with CMV: inspiratory and expiratory pause pressures, mean airway pressure, minute ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.

A Liquid Ventilator Prototype for Total Liquid Ventilation Preclinical Studies

“…In contrast, during total liquid ventilation (TLV), the lungs are completely filled with perfluorocarbon liquid while a dedicated device, called a liquid ventilator, must be used to periodically renew a liquid tidal volume in the lungs. A large number of preclinical studies involving various animal models of acute respiratory distress syndrome have demonstrated clear benefits from total liquid ventilation as compared to all other tested ventilation strategies, including partial liquid ventilation, conventional and high frequency gas ventilation (Hirschl et al, 1996;Wolfson et al, 2008). Among its several theoretical advantages over CMV, TLV is considered less aggressive for the lungs, due to lower positive inspiratory pressures and lower respiratory rates.…”

“…Research teams in TLV have mainly used bubble oxygenators Sekins et al, 1999;Tissier et al, 2009), commercial membrane oxygenators (Corno et al 2003;Larrabe et al, 2001;Hirschl et al, 1995;Wolfson et al, 1999Wolfson et al, , 2008 or have developed membrane oxygenators specifically for TLV (Tredici et al, 2004). However, the requirements for extracorporeal blood oxygenation appear irrelevant in TLV, since there is no mechanical stress to the blood (hemolysis) or bubble infusion in the blood (Iwahashi et al, 2004).…”

Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs

“…However, the use of liquid ventilation may be questioned by recent studies [5,6]; vaporization of PFCs offer new therapeutic options that make use of PFC protective and anti-inflammatory properties. These could entail PFC use in the prophylaxis or in the early treatment of acute lung injury.…”

“…uid ventilation for the treatment of experimental and clinical acute respiratory distress syndrome (ARDS) [1][2][3][4][5][6]. Despite promising results from early experimental and clinical trials [1][2][3][4] liquid ventilation failed in a recent phase III clinical trial [5].…”

Advantage of Prevention and Treatment in Neonatal Respiratory Distress Syndrome

“…髓过氧化物酶显著降低， 说明 TLV 在实施肺保护策略 上是有效的通气手段 [37] 。Pohlmann JR 等也对 TLV 与 CMV 治疗 RDS 进行了对照研究， 提示 TLV 组较 CMV 组可明显改善氧合，提高生存率 [38] 。但 TLV 相对于 …”