Resolution of Severe Ischemia–Reperfusion Injury Post–Lung Transplantation After Administration of Endobronchial Surfactant

Kermeen, F.; McNeil, Keith; Fraser, John F.; McCarthy, John J.; Ziegenfuss, Marc; Mullany, Daniel; Dunning, John; Hopkins, Peter

doi:10.1016/j.healun.2007.05.016

Cited by 43 publications

(35 citation statements)

References 20 publications

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“…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%

“…That study followed multiple uncontrolled case studies that also reported clinical improvements from exogenous surfactant therapy in adults and children after lung transplantation. [201][202][203] Controlled studies of surfactant therapy in children with ALI/ARDS have been more encouraging than those in adults. A randomized but unblinded trial by Willson et al 192 in 42 children with ALI/ARDS found that those who received calfactant (70 mg/kg) had immediate improvement in oxygenation and fewer ventilator days and days in intensive care.…”

Section: Human Studiesmentioning

confidence: 99%

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The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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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.

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Section: Human Studiesmentioning

confidence: 99%

Section: Human Studiesmentioning

confidence: 99%

Section: Human Studiesmentioning

confidence: 99%

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The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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“…Although data from the cardiac surgical literature does suggest an inflammatory effect from cardiopulmonary bypass, there is no evidence to suggest that bypass should be delayed when it is clearly indicated during transplantation (30,(34)(35)(36)(37)(38)(39).…”

Section: Operative and Perioperative Considerations In Lung Transplanmentioning

confidence: 99%

Lung Transplantation for Cystic Fibrosis

Adler

Aurora

Barker

et al. 2009

Proceedings of the American Thoracic Society

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“…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

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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.

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Resolution of Severe Ischemia–Reperfusion Injury Post–Lung Transplantation After Administration of Endobronchial Surfactant

Cited by 43 publications

References 20 publications

The Future of Exogenous Surfactant Therapy

The Future of Exogenous Surfactant Therapy

Lung Transplantation for Cystic Fibrosis

Beneficial effects of synthetic KL₄surfactant in experimental lung transplantation

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Resolution of Severe Ischemia–Reperfusion Injury Post–Lung Transplantation After Administration of Endobronchial Surfactant

Cited by 43 publications

References 20 publications

The Future of Exogenous Surfactant Therapy

The Future of Exogenous Surfactant Therapy

Lung Transplantation for Cystic Fibrosis

Beneficial effects of synthetic KL4surfactant in experimental lung transplantation

Contact Info

Product

Resources

About

Beneficial effects of synthetic KL₄surfactant in experimental lung transplantation