Surfactant replacement in reperfusion injury after clinical lung transplantation

Strüber, Martin; Hirt, Stephan; Cremer, J.; Harringer, Wolfgang; Haverich, Axel

doi:10.1007/s001340050967

Cited by 49 publications

(39 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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].…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Mühlfeld¹,

Schaefer²,

Becker³

et al. 2008

European Respiratory Journal

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…An additional 4 positive case series found clinical improvement from surfactant therapy but are not included in Table 2. [201][202][203][204] Figure 3 describes the clinical course of a representative child who received surfactant (calfactant) after near-drowning. 205 Near-drowning washes out pulmonary surfactant and is often accompanied by hypoxia and aspiration of gastric contents, which may lead to permeability lung injury.…”

Section: Human Studiesmentioning

confidence: 99%

“…The remaining 10 studies listed were uncontrolled treatment trials. Four case series [201][202][203][204] that found clinical improvement from exogenous surfactant after lung transplantation are not listed in this adults with ARDS secondary to sepsis and found no oxygenation improvement and no effect on morbidity or mortality. However, that study was flawed by the facts that colfosceril palmitate is a poor surfactant, and the aerosol technology they used delivered very little colfosceril palmitate to the alveoli.…”

Section: Human Studiesmentioning

confidence: 99%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

View full text Add to dashboard Cite

Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Key words: surfactant; infant respiratory distress syndrome; RDS; acute lung injury; ALI; acute respiratory distress syndrome; ARDS; neonatal. [Respir Care 2011;56(9):1369 -1386.

show abstract

“…In various experimental [8][9][10][11][12][13] and clinical [14][15][16][17][18] lung transplantation studies, animal-derived surfactants have been administered at different times over the course of the injury, either to the donor (before ischaemia) [8,10,12,13,16] or to the recipient (before [9][10][11]17] or after [12][13][14][15]18] reperfusion). Animal-derived surfactants consist of lipid extract preparations obtained from either bovine or porcine sources [19].…”

mentioning

confidence: 99%

Beneficial effects of synthetic KL₄surfactant in experimental lung transplantation

Sáenz¹,

Álvarez²,

Santos³

et al. 2010

Eur Respir J

View full text Add to dashboard Cite

The aim of this study was to investigate whether intratracheal administration of a new synthetic surfactant that includes the cationic, hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL 4 ), might be effective in reducing ischaemia-reperfusion injury after lung transplantation.Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL 4 surfactant at a dose of 25 mg total phospholipid?kg body weight -1 (2.5 mL?kg body weight -1) was instilled at 37uC to the donor left lung (n58) prior to explantation. Saline (2.5 mL?kg body weight -1 ; 37uC) was instilled into the donor left lung of the untreated group (n56). Lung function in recipients was measured during 2 h of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker and surfactant data. KL 4 surfactant treatment recovered oxygen levels in the recipient blood (mean¡SD arterial oxygen tension/inspiratory oxygen fraction 424¡60 versus 263¡101 mmHg in untreated group; p50.01) and normalised alveolar-arterial oxygen tension difference. Surfactant biophysical function was also recovered in KL 4 surfactant-treated lungs. This was associated with decreased C-reactive protein levels in BAL, and recovery of surfactant protein A content, normalised protein/ phospholipid ratios, and lower levels of both lipid peroxides and protein carbonyls in large surfactant aggregates.These findings suggest an important protective role for KL 4 surfactant treatment in lung transplantation.

show abstract

Surfactant replacement in reperfusion injury after clinical lung transplantation

Abstract: Surfactant replacement may become a clinical method for treatment of reperfusion injury after lung transplantation.

Cited by 49 publications

References 7 publications

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

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

The Future of Exogenous Surfactant Therapy

Beneficial effects of synthetic KL₄surfactant in experimental lung transplantation

Contact Info

Product

Resources

About

Surfactant replacement in reperfusion injury after clinical lung transplantation

Abstract: Surfactant replacement may become a clinical method for treatment of reperfusion injury after lung transplantation.

Cited by 49 publications

References 7 publications

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

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

The Future of Exogenous Surfactant Therapy

Beneficial effects of synthetic KL4surfactant in experimental lung transplantation

Contact Info

Product

Resources

About

Beneficial effects of synthetic KL₄surfactant in experimental lung transplantation