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Eur J Cardiothorac Surg 2009;35:304-312. doi:10.1016/j.ejcts.2008.09.050
Copyright © 2009, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.

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Surfactant pretreatment decreases long-term damage after ischemia-reperfusion injury of the lung

Niels P. van der Kaaija,*, Jolanda Kluina,1, Jack J. Haitsmab,2, Michael A. den Bakkerc, Bart N. Lambrechtd,3, Burkhard Lachmannb, Ron W.F. de Bruine,4, Ad J.J.C. Bogersa,4

a Department of Cardio-Thoracic Surgery, Erasmus MC Rotterdam, Rotterdam, The Netherlands
b Department of Anesthesiology, Erasmus MC Rotterdam, Rotterdam, The Netherlands
c Department of Pathology, Erasmus MC Rotterdam, Rotterdam, The Netherlands
d Department of Pulmonary Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands
e Department of Surgery, Erasmus MC Rotterdam, Rotterdam, The Netherlands

Received 29 April 2008; received in revised form 4 September 2008; accepted 18 September 2008.

* Corresponding author. Address: Department of Cardio-Thoracic Surgery, Erasmus MC Rotterdam, PO Box 1738, 3015GE, Rotterdam, The Netherlands. Tel.: +31 624816437; fax: +31 10 4089471. (Email: npvdkaaij{at}gmail.com).

Objective: Lung ischemia-reperfusion injury (LIRI) is a risk factor for primary acute graft failure following lung transplantation. LIRI hereby contributes to morbidity and mortality after lung transplantation. We have previously shown that surfactant pretreatment ameliorates LIRI up to 1 week after reperfusion. However, the impact of surfactant pretreatment on long-term outcome following LIRI is unknown. Therefore, the objective of this study was to investigate the effect of surfactant pretreatment on long-term outcome following LIRI. Methods: Male Sprague-Dawley rats (n = 63) were randomized to receive intratracheally administered porcine surfactant (400 mg/kg) or no pretreatment. One hour thereafter, animals underwent 120 min of warm ischemia by clamping the bronchus, pulmonary artery and vein of the left lung. A third group was sham-operated; a fourth group served as unoperated controls. Animals were killed on day 30 or 90 after surgery. Arterial oxygenation and lung compliance were determined. Broncho-alveolar lavage fluid (BALf) was collected to assess surfactant function and alveolar protein. Leukocyte infiltration was determined by flowcytometry in BALf, lung tissue and thoracic lymph nodes. Lungs of three animals per group were used for histological assessment. Results: Lung compliance was lower on day 30 and day 90 after LIRI than in sham-operated controls (day 30 V max 6.1 ± 2.1 vs 12.6 ± 1.3, day 90 6.9 ± 3.0 vs 12.1 ± 1.6; C max day 30 0.49 ± 0.17 vs 1.08 ± 0.21, day 90 0.67 ± 0.31 vs 1.11 ± 0.17). Furthermore, the number of CD45RA+-lymphocytes in left lung tissue was decreased on day 90 compared to unoperated animals (230.633 ± 96.770 vs 696.347 ± 202.909) and the number of macrophages elevated in left BALf on day 90. HE slides of LIRI animals were scored as fibroproliferative with moderate atelectasis. Surfactant pretreatment improved lung compliance (V max day 30 11.7 ± 1.8, day 90 11.1 ± 1.2; C max day 30 1.04 ± 0.23, day 90 1.16 ± 0.21) and normalized the number of CD45RA+-lymphocytes (769.555 ± 421.016) in left lung tissue. Furthermore lung architecture on HE slides was on return to normal. However, more CD5+CD4+-lymphocytes on day 30 (754.788 ± 97.269 vs 430.409 ± 109.909) and more macrophages on day 90 (2.144.000 ± 630.633 vs 867.454 ± 383.220) were measured in pretreated lung tissue compared to LIRI animals. Conclusions: Severe LIRI caused extensive pulmonary injury up to 90 days postoperatively. Surfactant pretreatment normalized pulmonary function, but resulted in an increased number of CD5+CD4+-cells and macrophages in lung tissue.

Key Words: Ischemia-reperfusion injury • Surfactant • Lung pathology • Animal model • Inflammatory cells • Experimental surgery







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Copyright © 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.