Lysis of Red Blood Cells and Alveolar Epithelial Toxicity by Therapeutic Pulmonary Surfactants

Findlay, Richard; Taeusch, H. William; David-Cu, Remedios; Walther, Frans J.

doi:10.1203/00006450-199501000-00006

Cited by 42 publications

(13 citation statements)

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“…In consequence, in the case of the totally synthetic surfactant Exosurf s hexadecanol and tyloxapol are added as ''spreading agents''. These substances have been shown to have a direct cytotoxic effect on erythrocytes (Findlay et al, 1995). Thomassen et al (1992) demonstrated inhibitory effects of Exosurf s on cytokine production of alveolar macrophages.…”

Section: Article In Pressmentioning

confidence: 98%

Influence of modified natural and synthetic surfactant preparations on bacterial killing by polymorphonuclear leucocytes

et al. 2004

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Section: Article In Pressmentioning

confidence: 98%

Influence of modified natural and synthetic surfactant preparations on bacterial killing by polymorphonuclear leucocytes

et al. 2004

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“…Also, the risk of pulmonary hemorrhage has been reported to increase after intratracheal treatment with colfosceril palmitate HSE (dipalmitoylphosphatidylcholine; Exosurf Neonatal; GlaxoSmithKline, Middlesex, UK) in extremely low-birth-weight infants with respiratory distress syndrome. This risk may be related to the cytotoxicity of tyloxapol (11). However, the mechanism it uses to induce cell death remains unknown.…”

Section: Introductionmentioning

confidence: 95%

“…Apoptosis is a form of programmed cell death characterized by cytoplasmic blebbing, condensation of nuclear chromatin, DNA fragmentation, exposure of phosphatidylserine residues on the outer leaflet, and cellular fragmentation into membrane apoptotic bodies (14,15). Tyloxapol has caused cell lysis or membrane porosity in previous studies, but tyloxapolinduced apoptosis has not been previously reported (4,5,11).…”

Section: Introductionmentioning

confidence: 96%

“…Also, tyloxapol has been used to augment nonviral gene transfer in a variety of eukaryotic cells, especially primary cells [e.g., human lung (NHBE) and porcine vascular endothelial (YPE) cells] that are difficult to transfect (5). Surfactants are known to interact with cell membranes, and tyloxapol has been reported to be toxic in epithelial and red blood cells (4,11). Also, the risk of pulmonary hemorrhage has been reported to increase after intratracheal treatment with colfosceril palmitate HSE (dipalmitoylphosphatidylcholine; Exosurf Neonatal; GlaxoSmithKline, Middlesex, UK) in extremely low-birth-weight infants with respiratory distress syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic Properties of Tyloxapol

2006

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“…Various mechanisms responsible for PH have been proposed, namely barotrauma, pressure changes in alveolar vessels, capillary fragility caused by extreme prematurity, and in surfactant-treated neonates, a possible toxic eect on cell membranes [3]. In conclusion a fundamental role seems to be played by the presence of a generalized bleeding diathesis, to which extremely preterm SGA infants are particularly prone.…”

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confidence: 98%

Pulmonary haemorrhage in infants with gestational age of less than 30 weeks

Carolis¹,

Romagnoli²,

Cafforio³

et al. 1998

European Journal of Pediatrics

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Abbreviations aPTT partial thromboplastin time á BW birth weight á GA gestational age á INR international normalized ratio á IVH intraventricular haemorrhage á PDA patent ductus arteriosus á PIE pulmonary interstitial emphysema á PH pulmonary haemorrhage á SGA small for gestational age Sir: Few studies have been conducted on pulmonary haemorrhage (PH) in premature infants and recently an increased incidence has been ascribed to surfactant use [5]. During two multicentre trials on the use of a natural surfactant preparation (Curosurf) [1, 2], we evaluated the frequency of PH and investigated prospectively the factors involved on its development in 97 neonates with gestational age (GA) <30 weeks. Forty neonates were randomly assigned to receive surfactant at birth: 22 neonates (GA = 28.3 0.8 weeks; birth weight (BW) = 934 299 g) received surfactant, 18 (GA = 27.8 1.6 weeks; BW = 908 215 g) air placebo [1]. Fifty-seven neonates (GA = 27.6 1.8 weeks; BW = 940 350 g) received Curosurf (200 mg/kg) as rescue therapy within the ®rst 24 h of life. PH was diagnosed when bright red blood was present in the endotracheal tube, in association with clinical deterioration and the appearance of new densities on the chest radiograph during the ®rst 3 days of life. A maximum of 3 days was selected to limit evaluation of eects of surfactant administration. During this period we reported clinical evidence of haemorrhage at sites other than lung as well as the presence of pulmonary interstitial emphysema (PIE), patent ductus arteriosus (PDA), intraventricular haemorrhage (IVH) and sepsis. Platelet count and coagulation tests (aPTT, INR and ®brinogen level) were carried out in all neonates, as soon as possible after birth and always within the ®rst 12 h of life. Statistical evaluation was made by Student's t-test and chi-squared test, using the Yates correction when necessary. Stepwise logistic regression analysis to assess the independent eect of a particular variable on the presence of PH was carried out.No statistically signi®cant dierence in the incidence of PH was found among the three groups: 18% (4/22) in the prophylactic group, 11% (2/18) in the control group and 11% (6/57) in the rescue group. PH occurred always between 24 and 72 h after birth and was the most frequent cause of death in the ®rst 72 h of life. Of the neonates with PH, (8/10) 80% died of severe pulmonary bleeding.To evaluate possible causes of PH other than surfactant administration we compared clinical and laboratory data of 10

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Lysis of Red Blood Cells and Alveolar Epithelial Toxicity by Therapeutic Pulmonary Surfactants

Cited by 42 publications

References 13 publications

Influence of modified natural and synthetic surfactant preparations on bacterial killing by polymorphonuclear leucocytes

Influence of modified natural and synthetic surfactant preparations on bacterial killing by polymorphonuclear leucocytes

Cytotoxic Properties of Tyloxapol

Pulmonary haemorrhage in infants with gestational age of less than 30 weeks

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