Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats.

Erasmus, Michiel E.; Petersen, Arjen H.; Hofstede, Gert Jan; Haagsman, Henk P.; Oetomo, Sidarto Bambang; Prop, Jochum

doi:10.1164/ajrccm.153.2.8564115

Cited by 49 publications

(54 citation statements)

References 49 publications

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“…Several studies have identified the important role of surfactant alterations in transplantationrelated I/R injury of the lung [8,9,[35][36][37][38][39][40]. Accordingly, exogenous surfactant therapy has been applied successfully in experimental [12][13][14][15][16][17][18][19][20][21] and clinical [22][23][24] studies. It is, therefore, considered a potentially promising therapy for the mitigation of severe lung I/R injury, although the optimal surfactant preparation and mode of therapy still need to be determined [26,41].…”

Section: Discussionmentioning

confidence: 99%

“…Several experimental [12][13][14][15][16][17][18][19][20][21] and clinical [22][23][24] studies give evidence that exogenous surfactant therapy successfully supplements the imbalanced endogenous surfactant system, serving to attenuate I/R injury and effectively improve lung preservation and graft function [11]. The great advantage of exogenous surfactant therapy of the donor in human lung transplantation is the fact that PGD in this case can accurately be predicted and, thus, even be prevented, providing a promising approach for prophylactic surfactant therapy [11,25,26].…”

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confidence: 99%

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Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Mühlfeld¹,

Schaefer²,

Becker³

et al. 2008

European Respiratory Journal

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The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model.Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4uC, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included ''worst case'' without Perfadex and surfactant (5), ''no injury'' without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (Ppa) were determined during reperfusion in groups 1 to 4.Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. Ppa did not differ between the groups.In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Mühlfeld¹,

Schaefer²,

Becker³

et al. 2008

European Respiratory Journal

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“…L -1 K + ) group was associated with superior ultrastructural preservation of tubular myelin. The percentage of the large aggregate subfraction in bronchoalveolar lavage studies represents a parameter that has been used as an indicator of surfactant function in acute lung injury [4,9,14,30]. Based on the current observations, the authors propose that the fraction of surface active tubular myelin, which largely corresponds to the bronchoalveolar lavage large aggregate subfraction [4], represents an important criterion for the assessment of the structural integrity of intraalveolar surfactant in studies investigating lung preservation quality.…”

Section: Discussionmentioning

confidence: 99%

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

et al. 2000

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Ischaemia/reperfusion (I/R) injury, a major problem in clinical lung transplantation, is associated with surfactant dysfunction. The present study aimed to test the hypothesis that preservation related improvements in post-ischaemic lung function are associated with improved ultrastructural preservation of pulmonary surfactant.Rat lungs were flush perfused with modified Euro-Collins solutions (ECS), stored for 2 h at 48C, and reperfused for 40 min. Lungs were preserved with conventional (ECS 115: 115 mmol . L -1 K + ), medium-K + (ECS 40: 40 mmol . L -1 K + ), or low-K + (ECS 10: 10 mmol . L -1 K + ) ECS. Functional parameters were monitored during reperfusion (n=10 per group). After reperfusion, left lungs were prepared for electron microscopical and stereological analysis of surfactant (n=5 per group).In all three experimental groups notable I/R injury developed which was lowest in ECS 40 as indicated by significantly less intraalveolar oedema, higher perfusate oxygenation, and lower peak inspiratory pressure. This was associated with a significantly superior preservation of the ultrastructure of the surface active surfactant subtype tubular myelin in ECS 40 compared with ECS 115 and ECS 10. Stereological analysis revealed that the relative amount of tubular myelin was highest in ECS 40 (mean SEM; 6.2 0.8%) compared with ECS 115 (3.0 1.0%) and ECS 10 (2.7 1.6%).Analysis of surfactant in its natural location within the organ showed that the severity of ischaemia/reperfusion injury correlates with differences in intraalveolar surfactant composition. Improved post-ischaemic respiratory function achieved by medium-K + Euro-Collins solution is associated with superior ultrastructural preservation of tubular myelin. It is concluded that the integrity of surface active tubular myelin represents an important criterion for the assessment of lung preservation quality. Eur Respir J 2000; 15: 526±531.

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“…Since 1966, experimental data generated in lung transplantation models have provided evidence for surfactant abnormalities and depletion after lung ischemia-reperfusion injury (LIRI) [1][2][3][4][5][6]. In 1998, Hohlfeld and colleagues demonstrated surfactant alterations in human lung transplant recipients, more than 1 year after transplantation [7].…”

Section: Introductionmentioning

confidence: 99%

Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung

Kaaij

Haitsma

Kluin

et al. 2005

European Journal of Cardio-Thoracic Surgery

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Objective: To investigate whether surfactant pretreatment provides lung protection in an animal model of lung ischemia-reperfusion injury (LIRI). Methods: Male Sprague-Dawley rats (nZ100) were randomised to receive intratracheally administered surfactant or no pretreatment. One hour thereafter, animals underwent 120 min of warm ischemia of the left lung, or were sham-operated. A third group served as healthy untreated controls. Animals were killed on day 1, 3 or 7. Blood gas values were measured and lung compliance was recorded. Broncho-alveolar lavage fluid (BALf) was obtained to assess the amount of alveolar protein, the ratio of small to large aggregate surfactant phospholipids (SA/LA ratio), and leukocyte infiltration (granulocytes, macrophages and lymphocytes, measured by Flow Cytometry). Results: LIRI resulted in a mortality rate of 17% and significantly decreased lung compliance and PaO 2 (day 1 and 3 P!0.001, day 7 P!0.05) as compared to sham-operated and healthy controls. On day 1 more protein was present in the alveoli of ischemic lungs (P!0.001) than in sham-operated and healthy controls. Furthermore, LIRI resulted in an increased SA/LA ratio in the left lung on day 1 (P!0.05) and caused infiltration of granulocytes (day 1, 3 and 7 (P!0.01)), macrophages (day 3 (P!0.05) and 7 (P!0.01) and lymphocytes (day 3 and 7 (P!0.01)) in the BALf as compared to sham-operated and healthy controls. Surfactant pretreatment improved survival, lung compliance (day 3 P!0.001) and PaO 2 (day 1, 3 (P!0.01 and 7 (P! 0.05)). It also reduced protein leakage (P!0.05) and prevented an increase in the SA/LA ratio (P!0.01). Although the number of macrophages and granulocytes in the BALF was increased on day 1 and 3 (P!0.01) after surfactant pretreatment as compared to all other groups, the number of lymphocytes was reduced on day 3 (P!0.05). Conclusions: The present study shows that surfactant pretreatment enhances recovery of lung function and lung mechanics after LIRI, resulting in normal parameters from day 3 onwards. Surfactant pretreatment in this LIRI model may provide useful information to improve donor lung function after lung transplantation. q

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Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats.

Cited by 49 publications

References 49 publications

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model

Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung

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