Impact of synthetic surfactant CHF5633 with SP‐B and SP‐C analogues on lung function and inflammation in rabbit model of acute respiratory distress syndrome

Mikolka, Pavol; Curstedt, Tore; Feinstein, Riccardo; Larsson, Anders; Grendár, Marian; Rising, Anna; Johansson, Jan

doi:10.14814/phy2.14700

Cited by 17 publications

(8 citation statements)

References 56 publications

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“…Therefore, we assessed IL-6 and IL-8 in our study. We found similar or even higher interleukin levels in BAL compared to other animal models of ALI (26,28,(32)(33)(34). Additionally, the amount of released mediators correlates with the severity and onset of ALI.…”

Section: In Ammationsupporting

confidence: 74%

Unilateral Acute Lung Injury in Pig: A Promising Animal Model

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Kainz

Zapletal

et al. 2022

Preprint

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Background Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions. Methods We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9%+Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS. Results After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and − 8 were increased in both lungs. Conclusions We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.

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Section: In Ammationsupporting

confidence: 74%

Unilateral Acute Lung Injury in Pig: A Promising Animal Model

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Kainz

Zapletal

et al. 2022

Preprint

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“…The positive effects of antiinflammatory applications on the development of postoperative adhesion have also been studied. Studies in the literature show that surfactant preparations in different tissues can prevent exaggerated inflammation with the immuno-regulation process [ 32 ]. Although its effect on intestinal inflammation has not been defined concretely, the development of an organized fibrotic process associated with advanced inflammation was reduced in all groups treated with surfactant preparation in our study.…”

Section: Discussionmentioning

confidence: 99%

The effect of natural surfactants on the development of postoperative intraabdominal adhesion

GÜLER,

KARAKAYA,

DOĞAN

et al. 2023

Turkish Journal of Medical Sciences

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Background/aim The development of postoperative adhesion after abdominal surgery is sometimes a severe problem. Our study investigates the effectiveness of exogenous surfactant application in preventing adhesion development in the experimental adhesion model. Materials and methods This randomized-controlled interventional study was carried out in the animal laboratory of Kahramanmaraş Sütçü İmam University between March 1 and March 31, 2020. An experimental intra-abdominal adhesion model was established in 24 adult female rats by cecal abrasion. Rats were randomly divided into four groups. Groups I, II, and III were taken intraperitoneally as beractant, poractant, and calfactant applied groups, respectively. Group IV was the control group. Relaparotomy was performed in all groups on the 15th postoperative day, and intra-abdominal adhesions were scored macroscopically according to the Canbaz scoring system. In addition, the cecal regions were evaluated microscopically and scored according to the Zühlke microscopic classification system. The scores of the groups were compared statistically. Results The Zühlke adhesion development score was significantly lower in the exogenous surfactant applied groups. In addition, when the surfactant-applied groups were compared among themselves, it was seen that the adhesion score in the beractant group was significantly better than the other surfactant types (p < 0.01). Conclusion Our study results showed that prophylactic intraperitoneal surfactant application significantly reduced postoperative adhesion development, particularly beractant.

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“…The artificial surfactant CHF5633 constitutes an interesting step forward in the development of synthetic preparations. Although various aspects still require testing, this wholly synthetic preparation containing SP-B and SP-C analogues has been shown to be as effective as Curosurf in a lamb model of ARDS and in clinical trials with preterm babies. ,,, Interestingly, the DPPC in CHF5633 was metabolized significantly more slowly in mice than was DPPC in Curosurf . This difference was attributed to the larger dose of DPPC (2.5 vs 1.75 mg/mouse), which arose because CHF 5633 contains only two PLs.…”

Section: Perspectives and Future Considerationsmentioning

confidence: 99%

“…BLES also has a similar PL profile as the starting bovine surfactant material but has most of the cholesterol removed during its preparation. Most synthetic surfactants, as exemplified in Table 1 by inclusion of the recently developed CHF5633, 62 include only 2 or 3 lipids and always contain a high percentage of DPPC. All these preparations in Table 1 contain hydrophobic surfactant proteins.…”

Section: Neonatal Respiratory Distress Syndromementioning

confidence: 99%

Pulmonary Surfactant: A Mighty Thin Film

Possmayer,

Zuo,

Veldhuizen

et al. 2023

Chem. Rev.

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Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorptiondriven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compressiondriven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.

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Impact of synthetic surfactant CHF5633 with SP‐B and SP‐C analogues on lung function and inflammation in rabbit model of acute respiratory distress syndrome

Cited by 17 publications

References 56 publications

Unilateral Acute Lung Injury in Pig: A Promising Animal Model

Unilateral Acute Lung Injury in Pig: A Promising Animal Model

The effect of natural surfactants on the development of postoperative intraabdominal adhesion

Pulmonary Surfactant: A Mighty Thin Film

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