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Title: Studies of partial liquid ventilation in a rabbit model of acute lung injury
Author: Kelly, Keith Patrick
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Introduction: Acute respiratory distress syndrome (ARDS) is a major cause of death on intensive care units. The syndrome is characterised by severe hypoxia, widespread atelectasis and decreased lung compliance, much of this impairment due to depletion and inhibition of surfactant. Therapy is supportive. For research purposes, many of the features of ARDS may be mimicked by a saline lavage model of lung injury. Perfluorocarbons have many characteristics similar to natural surfactants and have been used as an experimental means of supporting the injured lung, applied either by special liquid ventilators or as a hybrid technique with conventional gas ventilators known as partial liquid ventilation. Although nebulization is an accepted means of drug delivery, Perfluorocarbons had never been applied by a nebulized route to support the injured lung. Surfactant therapy has also been used to support the lung in the presence of ARDS. Surfactant preparations can be split into two broad categories; artificial surfactants containing no surfactant proteins and natural, but more expensive protein containing surfactants. There may be additional benefits of combining surfactant with Perfluorocarbons. Methods; This study examined the differences between saline lavaged lung injured rabbits, in the following treatment groups; i) control, ii) partial liquid ventilation i.e. poured perfluorocarbon PF 5080; iii) nebulized PF 5080, iv) the artificial surfactant Pumactant used in isolation, v) the natural porcine surfactant Curosurf used in isolation, vi) Pumactant used in combination with partial liquid ventilation and vii) Curosurf used in combination with partial liquid ventilation. The following end points were examined; a) Survival in saline lavaged rabbits to 12 hours, b) Differences in oxygenation between the treatment groups to 6 hours, c) Differences in dynamic compliance between the treatment groups to 6 hours, and static compliance between control, the Pumactant and the Curosurf groups, d) The appearance of computed tomography densities between the control, nebulized and partial liquid ventilation groups in frozen, ex- vivo lung preparations. Results; Survival to twelve hours in this study was greatest in the partial liquid ventilation alone or the combination of Pumactant with partial liquid ventilation. Oxygenation was improved by partial liquid ventilation, the natural surfactant Curosurf, or the combination of either Pumactant, or Curosurf with partial liquid ventilation. Dynamic compliance improved after partial liquid ventilation, Curosurf in isolation or the combination of Curosurf with partial liquid ventilation. Static compliance improved after treatment with Curosurf but not after treatment with Pumactant. There was a significant difference in density distributions in the CT scanning studies between the partial liquid ventilation and nebulized perfluorocarbon, and the control and partial liquid ventilation groups, but not between control and the nebulized groups implying little perfluorocarbon is delivered to the lungs by this route. Comments; In summary PF 5080 can be used for partial liquid ventilation in this model of lung injury to improve survival, oxygenation and lung mechanics. Using this method, nebulization of PF 5080 cannot be supported as it seems to have little effect on these end-points and may not be delivered in any significant amount to the respiratory tract. Curosurf is superior to Pumactant in improving oxygenation, and lung mechanics in this model of acute lung injury. There seems to be little difference between Curosurf and poured PF 5080 in terms of these endpoints. Whether partial liquid ventilation becomes more widespread in the support of the injured lung will depend on further research applications including means of application and trials in humans.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available