Inhaled aerosolised recombinant human activated protein C ameliorates endotoxin-induced lung injury in anaesthetised sheep

Waerhaug, Kristine; Kuzkov, Vsevolod V.; Kuklin, V. N.; Mortensen, Rica; Nordhus, K; Kirov, Mikhail Y.; Bjertnæs, Lars J.

doi:10.1186/cc7777

Cited by 29 publications

(27 citation statements)

References 30 publications

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“…85 Inhaled aerosolized activated protein C in a sheep model of ALI demonstrated improved oxygenation as well as lung aeration (as assessed by computed tomography scan). 86 b-Adrenergic agonists have potential benefits in that they accelerate the rate of alveolar fluid clearance by increasing cellular cyclic adenosine monophosphate, and they have antiinflammatory properties. 87 A randomized controlled trial in 40 patients with ALI showed a decrease in extravascular lung water and plateau airway pressure with intravenous salbutamol, although there was no difference in outcome.…”

Section: Fluids Inflammation and The Glycocalyxmentioning

confidence: 99%

Perioperative Lung Protection Strategies in One-lung and Two-lung Ventilation

Slinger¹

2015

ASA Refresher Courses in Anesthesiology

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Section: Fluids Inflammation and The Glycocalyxmentioning

confidence: 99%

Perioperative Lung Protection Strategies in One-lung and Two-lung Ventilation

Slinger¹

2015

ASA Refresher Courses in Anesthesiology

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“…Moreover, intravenous administration of rhAPC was reported to exert anticoagulant and antiinflammatory effects in the bronchoalveolar space of healthy humans challenged with LPS in a lung subsegment by bronchoscope [15,16]. Animal studies demonstrated that intrabronchially instilled APC exerts local anticoagulant and anti-inflammatory effects [21][22][23][24][29][30][31][32]. Considering the bleeding risk associated with intravenous APC, we here for the first time investigated the potential of intrabronchial rhAPC administration to inhibit coagulation and inflammation in the human lung, arguing that this route of delivery would circumvent serious side-effects [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses

et al. 2012

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Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied.Eight subjects received rhAPC via intrabronchial instillation by bronchoscope, while in a contralateral subsegment subjects received saline; all subjects were challenged bilaterally with LPS in the same lung subsegments. Four additional subjects received rhAPC (75 mg), with saline as a control in the contralateral subsegment, while they were bilaterally ''challenged'' with saline. After 6 h a bronchoalveolar lavage was performed and coagulation and inflammatory parameters were measured. rhAPC enhanced LPS-induced coagulation activation in the bronchoalveolar space, when compared with the control side. In addition, rhAPC amplified LPS-induced pro-inflammatory responses, as indicated by higher concentrations of cytokines and chemokines. rhAPC alone did not have procoagulant or proinflammatory effects.Locally administered rhAPC has unexpected procoagulant and pro-inflammatory effects in LPSchallenged lung subsegments. These data argue against a role for intrapulmonary delivery of rhAPC as a treatment strategy for lung inflammatory disorders in humans. @ERSpublications Observations made in the LPS-challenged lung question the use of rhAPC as therapy for lung inflammatory disorders

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“…96 Inhaled aerosolised activated protein C in a sheep model of ALI demonstrated improved oxygenation, as well as lung aeration, as assessed by computed tomography scan. 97 ß-adrenergic agonists have potential benefits as they increase the rate of alveolar fluid clearance by increasing cellular cyclic adenosine monophosphate and have antiinflammatory properties. 98 A randomised control trial in 40 patients with ALI showed a decrease in extravascular lung water and plateau airway pressure with intravenous salbutamol, although it showed no difference in outcome.…”

Section: Other Therapies For Lung Protectionmentioning

confidence: 99%

Are lung-protective ventilation strategies worth the effort?

Slinger

2013

Southern African Journal of Anaesthesia and Analgesia

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Nonphysiological ventilation in healthy lungs induces acute lung injury (ALI). Protective lung ventilation in patients with ALI improves outcome. Protective lung ventilation in noninjured lungs and in the absence of a primary pulmonary insult may initiate ventilation-induced lung injury (VILI), as evidenced by inflammatory markers. VILI has important implications that are remote to the lungs and may be associated with significant morbidity and mortality. Volatile anaesthetics can have a lungprotective effect. Excess fluids may contribute to perioperative lung injury. Anaesthesiologists manage a heterogeneous group of patients in the perioperative period, from patients with healthy lungs and patients with at-risk lungs through to patients with established ALI. More patients are at risk for ALI during surgery than previously thought. Appropriate perioperative management may prevent or ameliorate this lung injury. Although evidence is lacking from randomised controlled trials, applying protective ventilatory strategies seems to be a reasonable approach, based on the current understanding of mechanical ventilation and lung injury.

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Inhaled aerosolised recombinant human activated protein C ameliorates endotoxin-induced lung injury in anaesthetised sheep

Cited by 29 publications

References 30 publications

Perioperative Lung Protection Strategies in One-lung and Two-lung Ventilation

Perioperative Lung Protection Strategies in One-lung and Two-lung Ventilation

Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses

Are lung-protective ventilation strategies worth the effort?

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