We have previously documented alterations in endogenous surfactant after lung transplantation and improved graft function in some dogs after instillation of bovine lipid extract surfactant (bLES) into the recipient. To determine the effect of bLES delivery method and timing of treatment on physiologic response and surfactant recovery, 21 canine left lung grafts were divided into four groups: (1) Treatment of the donor for 3 h with aerosolized bLES prior to graft storage (Donor Aerosol); (2) Treatment of the recipient with instilled bLES immediately after transplantation (Recipient Instilled); (3) No bLES treatment (Control); and (4) Aerosolized bLES in donors and instilled bLES in recipients (Combined Therapy). Aerosolized bLES was labeled with [3H]-dipalmitoylphosphatidylcholine (DPPC) and instilled bLES with [14C]-DPPC. Grafts were stored for 36 h, transplanted and reperfused for 6 h. The native right and transplanted left lungs were then lavaged and protein yield, surfactant aggregates, and bLES recovery were measured. After 6 h of reperfusion, PO2/FlO2 ratio was significantly better after Combined Therapy (372 +/- 52 mm Hg) than in the Recipient Instilled (117 +/- 47 mm Hg) and Control groups (87 +/- 26 mm Hg), with intermediate values in Donor Aerosol dogs (232 +/- 64 mm Hg). The recovery of donor aerosolized bLES from transplanted lungs was increased in dogs given Combined Therapy versus Donor Aerosol treatment alone (p = 0.03). Furthermore, with Combined Therapy there was an increased percentage of instilled bLES recovered from transplanted lungs compared with the Recipient Instilled group. We conclude that surfactant treatment strategies influence physiologic response and bLES recovery after prolonged lung preservation. Treatment of lung donors with exogenous surfactant prior to graft storage was associated with less severe lung injury. Combined donor and recipient bLES therapy resulted in a superior physiologic response during reperfusion in this model.
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http://dx.doi.org/10.1164/ajrccm.154.1.8680706 | DOI Listing |
Lung
December 2020
Department of Physiology and Pharmacology, Western University, London, ON, Canada.
Background: Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery.
View Article and Find Full Text PDFPaediatr Child Health
August 2019
Children's Hospital, London Health Science Centre, Department of Pediatrics, Western University, London, Ontario.
Background: Surfactant delivery via a thin endotracheal catheter during spontaneous breathing, a technique called minimally invasive surfactant therapy (MIST), is an alternative to intubation and surfactant administration. There is paucity of data regarding the administration of high-volume surfactant using this technique.
Methods: We conducted a retrospective cohort study to review the safety, efficacy, and procedural details pertaining to the delivery of 5 mL/kg of BLES® via MIST approach.
BMC Pulm Med
November 2013
Department of Physiology & Pharmacology, Western University, London, Ontario, Canada.
Background: Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.
Methods: Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control.
Crit Care Med
May 2011
Department of Pediatrics, Université de Sherbrooke, Sherbrooke, Canada.
Objective: To test the hypothesis that total liquid ventilation enables a more effective and better tolerated lavage than a bronchoalveolar lavage performed with diluted surfactant in a newborn ovine model of severe acute meconium aspiration syndrome.
Design: Prospective, randomized, interventional study.
Setting: Animal research laboratory at the Faculté de médecine et des sciences de la santé de l'université de Sherbrooke, Sherbrooke, Canada.
J Appl Physiol (1985)
May 2004
Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada N6A 4V2.
Pulmonary surfactant is a mixture of phospholipids ( approximately 90%) and surfactant-associated proteins (SPs) ( approximately 10%) that stabilize the lung by reducing the surface tension. One proposed mechanism by which surfactant is altered during acute lung injury is via direct oxidative damage to surfactant. In vitro studies have revealed that the surface activity of oxidized surfactant was impaired and that this effect could be overcome by adding SP-A.
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