Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation

Okayama University, Okayama, Okayama, Japan
The Annals of Thoracic Surgery (Impact Factor: 3.85). 02/1999; 67(2):332-9. DOI: 10.1016/S0003-4975(98)01136-9
Source: PubMed


This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation.
The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed.
All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group.
The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.


Available from: Hideki Itano
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung transplantation recently marked its 35th anniversary. The period has been marked by 20 years of initially slow progress and by 15 years of explosive growth and success. Critical care management of lung transplant recipients is predominantly supportive. The patient¿s vital functions are sustained until the trasplanted organ assumes reasonable function. Immediate postoperative intensive care unit (ICU) concerns centre upon an evaluation of the trasplanted lung function and its effect on other organ systems. Knowledge of the specific postoperative complications (hypoxia, rejection, infection, weaning, etc). unique to the lung transplant and anticipation of problems related to these conditions are important requirements for a successful postoperative course. Finally, it will be described nutritional support and general management protocols in order to achieve agreements.
    Revista Colombiana de Anestesiologia 01/2000; XXVIII(4):-.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die Anwendung von Perfluorkarbonen in der Behandlung des akuten Lungenversagens (ARDS) ist eine viel versprechende Therapieoption. Perfluorkarbone weisen bedingt durch die Eigenschaften der C–F Atombindung spezifische Charakteristika auf, die eine intraalveoläre Anwendung ermöglichen und bei einer geschädigten Lunge positive Effekte auf den Gasaustausch und die pulmonale Mechanik zeigen. In den bisherigen Anwendungsformen TLV und PLV werden verschiedene Mechanismen der Verbesserung der pulmonalen Funktion diskutiert: Rekrutierung von Alveolen, Verhinderung des Alveolenkollaps (Derecruitment) (“Liquid-PEEP”), Surfaktantwirkung, Umverteilung der Perfusion, antiinflammatorische Effekte. Während die Totale Flüssigkeitsbeatmung aufgrund ihrer technischen Komplexität bislang nur experimentell zum Einsatz kam, wurde die Partial-Liquid-Ventilation bereits erfolgreich in klinischen Studien eingesetzt. Im Rahmen dieser klinischen Studien wurden jedoch unerwünschte Effekte der PLV beobachtet, die mit der intraalveolären Anwendung von Perfluorkarbonen als Flüssigkeit assoziiert sind. Eine Applikation von Perfluorkarbon in Dampfform, in Analogie zur Inhalationsanästhesie könnte diese Problematik lösen. Von unserer Arbeitsgruppe wurde dieser Therapieansatz technisch realisiert und in einem Modell einer akuten Lungenschädigung untersucht. Die Perfluorkarbonverdampfung führte zu einer signifikanten Verbesserung von Compliance und Oxygenierung. Aus der Beobachtung dieser positiven Effekte in einem Modell einer akuten Lungenschädigung ergeben sich neue wissenschaftliche Fragestellungen. Die Klärung des kausalen Wirkungsmechanismus von Perfluorhexandampf ist dabei ebenso wichtig wie Fragen bezüglich Dosis-Wirkungsbeziehung und Dosierungszeitpunkt, antiinflammatorischer Effekte, oder einer Interaktion von Perfluorhexan mit Surfaktant. Dieser Therapieansatz unter Verwendung von etablierter anästhesiologischer Technologie bietet die Möglichkeit einer exakten Dosierung und bedarfsadaptierten Applikation von Perfluorkarbonen. Die ermutigenden Resultate der PFC-Verdampfung lassen auf eine viel versprechende Behandlungsalternative beim akuten Lungenversagen hoffen. The introduction of Perfluorochemicals into medicine and especially into the treatment of severe lung injury is a fascinating scientific task. Many recall the famous experiments from Clark et al. in 1966 when he demonstrated “liquidventilation with perfluorocarbons” in the mammal species for the first time. After this hallmark, perfluorocarbons were subsequently introduced in research of acute lung injury by the techniques of Total- and Partial-Liquid-Ventilation (TLV; PLV). Perfluorocarbons (saturated organofluorids) have unique chemical and physical properties which made them attractive substances for intraalveolar application. The strong C–F bindings in the perfluorocarbon molecules are responsible for their chemical stability, biochemical inertness, high capacity to dissolve respiratory gases, low surface tension and high vapor pressures. Furthermore, the high density of the PFC lead to radio-opacity and their distribution to dependent lung areas. The efficacy of PFC liquid, applied by TLV/PLV has been demonstrated in numerous animal studies using different models of acute lung injury. Currently, several mechanisms of action of perfluorocarbon fluids in acute lung injury are discussed: recruitment of atelectatic alveoli, prevention of endexpiratory collapse of alveoli (“liquid PEEP”), redistribution of perfusion, oxygen transport, surfactant like effects and decrease of inflammation. Since total liquid ventilation has been used only in experimental models of lung injury, partial liquid ventilation has been introduced successfully into clinical trials (phase I–II). However, the results of the first randomised, controlled study of PLV in 90 adult patients suffering from severe respiratory failure (ALI/ARDS) showed no differences between PLV and conventional treatment. Furthermore, the instillation of relatively large amounts of liquid into the lungs poses several technical challenges and may be associated with complications such as liquithoraces, pneumothoraces and hypoxia. Since mammal lungs are evolutionary specialised to gas exchange using atmospheric oxygen, the application of liquids, even if they transport respiratory gases very well is not physiologic. To overcome these unwanted side effects, we developed a technique of perfluorocarbon vaporisation in analogy to the application of inhalation anaesthetic agents. After resolving some technical issues, this application technique was used successfully in an animal model of acute lung injury. Vaporisation of perfluorohexane in a concentration of 18 Vol.% of inspired gas improved significantly oxygenation and lung compliance. Though these results are promising, mechanisms of action, dose-efficacy relation, surfactant-perfluorocarbon interaction or anti-inflammatory effects of vaporised perfluorohexane are still unclear. These questions need to be clarified before this technique can be applied clinically. However, the inhalation of vapor, a technique already familiar to anaesthesiologists should avoid risks of large amounts of fluids in the bronchoalveolar space. Furthermore, this technique can be administered by established anaesthetic equipment with the advantage of exact dosing, continuous monitoring, and demand application in a way near to clinical routine.
    Der Anaesthesist 01/2000; 49(4):291-301. DOI:10.1007/s001010050831 · 0.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liquid ventilation using Perflubron has been investigated for more than 30 years. Many investigators demonstrated beneficial effects of liquid ventilation in the setting of respiratory failure in animals. It is thought that liquid ventilation could be a new treatment for acute respiratory distress syndrome (ARDS). There are two methods in liquid ventilation. One is total liquid ventilation (TLV), in which the lungs are filled with Perflubron. The other one is, so to speak, partial liquid ventilation (PLV), in which the lungs are partially filled with Perflubron. Nowadays, partial liquid ventilation is applied in many animal studies and clinical trials, although total liquid ventilation is applied only in animal studies. Liquid ventilation using Perflubron has beneficial effects on gas exchange and a lung lavage effect in ARDS. In the rabbit model of respiratory failure induced by lung lavage, PLV produced significant improvement in blood gas compared with gas ventilation (GV) (PaO2 50±8 mmHg in GV, 225±91 mmHg in PLV; PaCO2 68±7 mmHg in GV, 44±5 mmHg in PLV). PLV also caused a decrease in myeloperoxidase (MPO) activity in a lung transplantation study in dogs (0.77±0.5 in GV, 0.38±0.25 in PLV). It is suggested that liquid ventilation might have an anti-inflammatory and lung protective effect. It is likely that liquid ventilation is a reasonable alternative. However, details of liquid ventilation, such as indications, management technique, and interaction with current therapy, are still unclear.
    Journal of Artificial Organs 09/2001; 4(3):188-192. DOI:10.1007/BF02479892 · 1.44 Impact Factor
Show more