Improved gas exchange and survival after KL‐4 surfactant in newborn pigs with severe acute lung injury

Zimmermann, Anna M.; Roberts, Kari D.; Lampland, Andrea; Meyers, Pat A.; Worwa, Cathy; Plumm, Brenda; Pacheco, M. Cristina; Wolfson, Marla R.; Mammel, Mark C.

doi:10.1002/ppul.21252

Cited by 18 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The success of rescue therapy for chemical-induced ALI using synthetic surfactant with advanced and robust SP-B and SP-C mimics represents a significant breakthrough, as previous experiments have indicated only minimal or no improvement in lung function with animal-derived and first generation synthetic surfactant preparations (Lamm & Albert, 1990; Brackenbury et al, 2001; Zimmermann et al, 2010; Lampland et al, 2014). Lamm & Albert (1990) tested Survanta, a modified natural surfactant based on a bovine lung extract, in rabbit lungs after intratracheal injection of HCl, but found no improvement in arterial oxygenation.…”

Section: Discussionmentioning

confidence: 99%

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Walther

Hernández-Juviel

Gordon

et al. 2014

PeerJ

View full text Add to dashboard Cite

Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical) ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C) mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB), a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight), the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS) assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary-alveolar protein leakage and surfactant dysfunction after HCl instillation than following lung lavage. At the end of the duration of the experiments, synthetic surfactants provided more clinical stability in ALI/ARDS than Infasurf, and the protein content of bronchoalveolar lavage fluid was lowest for the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA.Conclusion. Advanced synthetic surfactant with robust SP-B and SP-C mimics is better equipped to tackle surfactant inactivation in chemical ALI than synthetic surfactant with only a single surfactant peptide or animal-derived surfactant.

show abstract

Section: Discussionmentioning

confidence: 99%

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Walther

Hernández-Juviel

Gordon

et al. 2014

PeerJ

View full text Add to dashboard Cite

show abstract

“…Scoring of lung injury was performed by a pathologist blinded to the experimental design using a semiquantitative scoring system. Pathological signs of lung injury, namely, alveolar and interstitial inflammation, alveolar and interstitial hemorrhage, edema, atelectasis, and necrosis, were each scored on a 0-4-point scale: 0: no injury; 1: injury to 25% of the field; 2: injury to 50% of the field; 3: injury to 75% of the field; and 4: injury across the field (40).…”

Section: Sp-b and Sp-c Concentrationsmentioning

confidence: 99%

Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome

et al. 2013

View full text Add to dashboard Cite

“…Once anesthetized, mice were removed from the induction chamber and placed in a supine position and 100 μl of instillate (total dose) delivered drop-wise to the nares using a pipette. Approximate 120 mg/kg TPL of KL 4 surfactant was delivered per dose, a dose that has been shown to be effective in the ALI and respiratory distress syndrome models in restoring lung function and modulating an immune response (19, 21, 22). After treatment, mice were allowed to recover in a warm environment under observation prior to being returned to their home cage.…”

Section: Methodsmentioning

confidence: 99%

“…KL 4 surfactant (lucinactant), a peptide containing synthetic surfactant used as an endogenous surfactant replacement therapy (14, 15), can function locally in an inflammatory milieu in the lung and can also modulate the immune response, including limiting cytokine activation (16–21), as we have previously shown in other reported models of acute lung injury (22, 23). Since KL 4 surfactant can function in an inflammatory milieu, and reduces cytokine activation and neutrophil influx into the lungs, it is a potentially promising therapeutic approach for mitigating radiation-induced lung disease.…”

Section: Introductionmentioning

confidence: 99%

Radiation Mitigating Properties of Intranasally Administered KL₄Surfactant in a Murine Model of Radiation-Induced Lung Damage

Christofidou‐Solomidou

Pietrofesa

Arguiri

et al. 2017

Radiation Research

View full text Add to dashboard Cite

The threat of exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions is a significant public health concern. The lung is particularly susceptible to radiation-induced injury from external sources or inhalation of radioactive particles from radioactive fallout. Radiation-induced lung disease can manifest with an acute radiation pneumonitis and/or delayed effects leading to pulmonary fibrosis. As prior warning of radiation exposure is unlikely, medical countermeasures (MCMs) to mitigate radiation-induced lung disease that can be given in mass-casualty situations many hours or days postirradiation are needed to prevent both early and late lung damage. In this study, KL4 surfactant (lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage. Here, 120 mg/kg total phospholipid of KL4 surfactant was administered twice daily intranasally, (enabling intrapulmonary inhalation of drug) to C57BL/6 mice 24 h after a single 13.5 Gy dose of thoracic irradiation (LD50 dose). Both early and chronic phase (2 and 4 weeks and 18 weeks postirradiation, respectively) assessments were performed. Mice were evaluated for evidence of reduced arterial blood oxygenation and early and chronic lung and systemic inflammation, lung fibrosis and oxidative stress. Analysis was done by performing lung function/respiration dynamics and measuring cellular protein content of bronchoalveolar lavage fluid (BALF), and levels of cytokines, 8-iso-prostaglandin F2α, hydroxyproline in lung and plasma, along with evaluating lung histology. The results of this study showed that intranasal delivery of KL4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF, as were plasma pro-inflammatory cytokine levels and biomarker of oxidative stress. KL4 surfactant is a promising MCM for mitigation of lung tissue damage after targeted, thoracic irradiation and has the potential to be developed as a broad-spectrum, multi-use MCM against chemical, biological, radiological or nuclear threat agents with potential to cause lung injury.

show abstract

Improved gas exchange and survival after KL‐4 surfactant in newborn pigs with severe acute lung injury

Abstract: In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival.

Cited by 18 publications

References 26 publications

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome

Radiation Mitigating Properties of Intranasally Administered KL₄Surfactant in a Murine Model of Radiation-Induced Lung Damage

Contact Info

Product

Resources

About

Improved gas exchange and survival after KL‐4 surfactant in newborn pigs with severe acute lung injury

Abstract: In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival.

Cited by 18 publications

References 26 publications

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome

Radiation Mitigating Properties of Intranasally Administered KL4Surfactant in a Murine Model of Radiation-Induced Lung Damage

Contact Info

Product

Resources

About

Radiation Mitigating Properties of Intranasally Administered KL₄Surfactant in a Murine Model of Radiation-Induced Lung Damage