Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract

Kobayashi, Tsutomu; Ohta, Keisuke; Tashiro, Katsumi; Nishizuka, Kazuo; Chen, Weimin; Ohmura, Shigeo; Yamamoto, Ken

doi:10.1152/jappl.1999.86.6.1778

Cited by 63 publications

(64 citation statements)

References 27 publications

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“…For surfactants improved by addition of PEG or other polymers (12,17,19,35) to be clinically useful, our data, coupled with the observations of Campbell et al (23), indicate that careful matching of surfactant quality with the specific intraalveolar pathology may be necessary as implied by the work of Puligandla et al (22). This approach may in time significantly improve surfactant therapy for ALI/ARDS.…”

Section: Discussionsupporting

confidence: 53%

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

Dehority

Clements

et al. 2005

Pediatr Res

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Addition of ionic and nonionic water-soluble polymers to pulmonary surfactants in the presence of inactivating substances prevents surfactant inactivation in vitro and improves lung function in several models of lung injury. However, a recent report found opposite effects when surfactant plus polyethylene glycol (PEG) was used to treat lung injury caused by saline lung lavage. Therefore, we examined the reasons why the polymer effect is less evident in the saline lung lavage lung injury model. We treated rats with lavage lung injury with a commercial lung surfactant extract derived from bovine lung (Survanta) with or without addition of PEG. Groups treated with Survanta ϩ PEG had significantly higher static post mortem lung volumes than groups treated with Survanta. However, groups treated with Survanta ϩ PEG had more tracheal fluid and no significant benefit in arterial oxygenation compared with the group treated with Survanta, despite our use of measures to reduce pulmonary edema. Measurements after intravascular injections of 125 I-labeled albumin confirmed that addition of PEG increased extravascular lung water and that this effect is mitigated by furosemide. We conclude that surfactant ϩ PEG mixtures are less effective in lavage injury than in other forms of lung injury because of increased extravascular lung water. ALI results from a variety of insults as diverse as meconium aspiration in newborns, hydrochloric acid reflux, sepsis, and ventilator trauma. In turn, injury predisposes the patient to acute (or adult) respiratory distress syndrome (ARDS) (1-4). Pulmonary surfactant replacement, now a mainstay in the treatment of respiratory distress syndrome in premature infants, has not enjoyed comparable success in treating ARDS (5-7). Inadequate dosage or distribution, and inactivation of surfactant have been postulated for its poor performance in treating these injuries (8 -11).Multiple reports indicate improved surfactant function when polymers such as dextrans, PEG, and hyaluronan are added to surfactant preparations in vitro (12-15). Animals with ALI have improved lung function when treated with surfactant polymer mixtures versus surfactant alone. found that adult rats receiving surfactant ϩ PEG, dextran, or hyaluronan mixtures have better gas exchange, pulmonary mechanics, and histologic appearance of the lungs when compared with rats treated with Survanta (beractant) alone after HCl-, meconium-, and endotoxin-induced lung injuries. Kobayashi et al. (19,20) have shown that addition of dextran to surfactant improves responses in two additional lung injury models (albumin inhibition in immature rabbits and acid milk aspiration in rats).The specific model used to induce ALI, however, may affect treatment responses to surfactant and surfactant ϩ PEG, as different models of lung injury produce different alveolar environments. A lavage model of lung injury, for example, removes variable amounts of alveolar surfactant (21), whereas a meconium model of lung injury inactivates but does not remove surfactant. P...

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Section: Discussionsupporting

confidence: 53%

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

Dehority

Clements

et al. 2005

Pediatr Res

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“…25 mg/mL reported by Ishizaka et al (20). However, previous in vitro studies have shown that at such a concentration albumin was sufficient to inactivate a dilute lung surfactant preparation, such as the 0.5 mg/mL BLES used here (2,4).…”

Section: Methodsmentioning

confidence: 87%

“…Both in vitro (1)(2)(3)(4)(5)(6) and in vivo (7)(8)(9) trials have shown that these nonionic polymers can significantly improve the surface activity of different therapeutic lung surfactants and effectively reverse inactivation due to a variety of inhibitory substances.…”

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confidence: 99%

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

et al. 2006

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ABSTRACT:Chitosan is a natural, cationic polysaccharide derived from fully or partially deacetylated chitin. Chitosan is capable of inducing large phospholipid aggregates, closely resembling the function of nonionic polymers tested previously as additives to therapeutic lung surfactants. The effects of chitosan on improving the surface activity of a dilute lung surfactant preparation, bovine lipid extract surfactant (BLES), and on resisting albumin-induced inactivation were studied using a constrained sessile drop (CSD) method. Also studied in parallel were the effects of polyethylene glycol (PEG, 10 kD) and hyaluronan (HA, 1240 kD). Both adsorption and dynamic cycling studies showed that chitosan is able to significantly enhance the surface activity of 0.5 mg/mL BLES and to resist albumin-induced inactivation at an extremely low concentration of 0.05 mg/mL, 1000 times smaller than the usual concentration of PEG and 20 times smaller than HA. Optical microscopy found that chitosan induced large surfactant aggregates even in the presence of albumin. Cytotoxicity tests confirmed that chitosan has no deleterious effect on the viability of lung epithelial cells. The experimental results suggest that chitosan may be a more effective polymeric additive to lung surfactant than the other polymers tested so far. (1) suggested the use of low-cost, water-soluble nonionic polymers, such as dextran, PEG, and polyvinylpyrrolidone (PVP), as additives to therapeutic lung surfactants. Both in vitro (1-6) and in vivo (7-9) trials have shown that these nonionic polymers can significantly improve the surface activity of different therapeutic lung surfactants and effectively reverse inactivation due to a variety of inhibitory substances.More recently, Lu et al. (10,11) reported the use of an anionic polymer, HA, as a surfactant additive. Both in vitro (10) and in vivo (11) tests showed that the addition of HA at different molecular weights to various therapeutic lung surfactants can effectively reverse serum-and meconium-induced inactivation. These studies, therefore, tentatively proved the feasibility of using an ionic polymer as a lung surfactant additive. Following these studies, we investigate here the use of a cationic polymer, chitosan, as a potential lung surfactant additive.Chitosan is a natural polysaccharide composed of linear ␤-(1¡4)-linked 2-amino-2-deoxy-␤-D-glucan combined with glycosidic linkages (12). It is derived from fully or partially deacetylated chitin, which is extracted from crustacean shells. Chitosan is also a polyelectrolyte with a positively charged backbone and is readily soluble in slightly acidic conditions (12). Chitosan was proven to be biodegradable, biocompatible, bioadhesive, and nontoxic in a range of toxicity tests (13). Because of these desirable properties, it has been extensively used in a variety of food, cosmetic, and pharmaceutical fields. Specifically, chitosan has been extensively used in drug delivery (13), including pulmonary drug delivery (12).Chan and co-workers (14 -17) have recently...

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“…Existem alguns experimentos in vitro que demonstraram que o dextram além de apresentar um efeito protetor, potencializaria a ação do surfactante 28,29 . Alguns dos animais de nosso experimento pertenciam também a este estudo em paralelo que pretendia avaliar esta possibilidade in vivo.…”

Section: Antes De Discutirmos Esses Resultados Julgamos Pertinente Qunclassified

“…Houve quatro coelhos (peso médio de 3,00 +0,14 kg) que receberam extrato de surfactante bovino (27 mg/ml) na dose de 1 ml/kg associados com 2 ml de Dextran (peso molécula de 70.000) na concentração de 50mg/ml. O Dextran foi associado para explorar a possibilidade de aumento da atividade do surfactante conforme demonstrado em alguns estudos in vitro 28,29 Após a lavagem pulmonar, a PaO 2 média no grupo submetido à ventilação convencional associada à reposição de surfactante (CMV+S) foi de 43,6 +9,9 mmHg sem apresentar diferença (p=0,154) quando comparado com os coelhos submetidos à ventilação de alta freqüência por Em ambos os grupos, após a lavagem pulmonar, a pressão média nas vias aéreas (MAP) era a mesma (p=0,980). Entretanto, aos 15, 60 e 120 minutos após serem alocados para HFO ou CMV+S, observou-se que o grupo CMV+S apresentou uma MAP significativamente menor (p<0,001).…”

Section: Métodosunclassified

High frequency oscillation ventilation compared to conventional mechanical ventilation plus exogenous surfactant replacement in rabbits

Piva¹,

Chatrkaw²,

Choong³

et al. 2000

J Pediatr (Rio J)

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ResumoObjetivos: a) avaliar o efeito na oxigenação e ventilação de coelhos artificialmente depletados de surfactante quando submetidos à ventilação mecânica convencional associada à reposição parcial de surfactante exógeno; b) comparar a evolução deste grupo com outro grupo submetido à ventilação de alta freqüência por oscilação (HFO) sem reposição associada de surfactante.Métodos: Vinte coelhos brancos da raça New Zealand, peso de + 3 kg, foram anestesiados e artificialmente induzidos à depleção de surfactante endógeno através de sucessivas lavagens pulmonares com alíquotas (25 ml/kg) de solução fisiológica, até atingir uma PaO 2 menor que 100 mmHg, quando ventilados via traqueostomia no modo de pressão controlada objetivando um volume corrente de 10ml/kg, com PEEP de 5cm H 2 O, FiO 2 de 100%, freqüência respiratória de 30 mpm, e tempo inspiratório de 0,65 s. Posteriormente, os coelhos foram divididos em (a) grupo CMV+S, submetido à ventilação convencional associada com reposição parcial de surfactante exógeno; (b) grupo HFO submetido à ventilação de alta freqüência por oscilação. Gasometrias arteriais foram coletadas antes da lavagem pulmonar, após a lavagem pulmonar, 15, 60 e 120 minutos após iniciado o tratamento. Os grupos foram comparados utilizando-se o teste t de Student.Resultados: Em ambos grupos a PaO 2 (pós lavagem pulmonar) era inferior a 50mmHg (p=0,154), subindo aos15 minutos de tratamento para 254 mmHg (CMV+S) e 288 mmHg (HFO, p=0,626). Aos 60 e 120 minutos, a PaO 2 foi maior (p=0,001) no grupo HFO (431 e 431 mmHg) quando comparado com o grupo CMV+S, que apresentou queda progressiva (148 e 126 mmHg). Aos 60 minutos a PaCO 2 era significativamente menor no grupo do CMV+S (29 versus 41 mmHg).Conclusões: Em modelo animal com SARA a estratégia de ventilação protetora como a HFO, isoladamente, promove uma rápida e persistente melhora na oxigenação, inclusive, com níveis superiores aos obtidos pelos animais submetidos à ventilação mecâ-nica convencional associada à reposição de surfactante. AbstractObjectives: (a) to evaluate the effect on oxygenation and ventilation of rabbits with induced surfactant depletion when they are submitted to a conventional mechanical ventilation, plus a small dose of exogenous surfactant; (b) to compare this group with another group submitted to a High Frequency Oscillation (HFO) without exogenous surfactant administration.Methods: Twenty New Zealand White rabbits weighing (+ 3 kg) were anaesthetized and artificially induced to a endogenous surfactant depletion by successively lung lavage with normal saline (aliquots of 25 ml/kg) until to reach a persistent PaO 2 less than 100 mmHg when submitted to a mechanical ventilation in a pressure control mode with a target tidal volume of 10ml/kg, PEEP of 5cm H 2 O, FiO 2 1.0, respiratory rate 30/min, and inspiratory time of 0.65 s. Then the rabbits were divided in (a) CMV+S group, submitted to a conventional mechanical ventilation plus exogenous surfactant replacement; (b) HFO group, submitted to a High Frequency Oscillation Vent...

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Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract

Cited by 63 publications

References 27 publications

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

High frequency oscillation ventilation compared to conventional mechanical ventilation plus exogenous surfactant replacement in rabbits

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