Morphology and Function of Pulmonary Surfactant Inhibited by Meconium

Bae, Chong‐Woo; Takahashi, Akio; Chida, Shoichi; Sasaki, Mika

doi:10.1203/00006450-199808000-00008

Cited by 67 publications

(43 citation statements)

References 23 publications

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“…It has been shown previously that meconium interferes with surfactant function (25,26). Whereas some experimental studies (27,28) and uncontrolled case series in human infants (29) suggest a beneficial effect of exogenous surfactant treatment, others do not (30).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Breathing during Partial Liquid Ventilation in Animals with Meconium Aspiration

et al. 2001

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Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO 2 (14.5 Ϯ 4.5 versus 25.6 Ϯ 6.7 kPa; p Ͻ 0.01; GV versus PLV) and lung compliance (4.3 Ϯ 0.4 versus 6.1 Ϯ 1.2 mL·kPa -1 ·kg -1 ; p Ͻ 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 Ϯ 2.8 versus 3.5 Ϯ 1.5 mL·kPa·kg -1 ; p Ͻ 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO 2 (3.9 Ϯ 0.5 versus 4.5 Ϯ 0.7 kPa; p Ͻ 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation. Previous studies have shown that PLV can improve gas exchange in animals and human neonates with severe lung disease (1-4). In most studies, PLV has been tested in pharmacologically paralyzed subjects and not during preserved spontaneous respiratory activity. However, there are potential disadvantages of neuromuscular blockade in ventilated infants, such as atrophy of respiratory muscles (5), impaired pulmonary mechanics (6), and a lower functional residual capacity resulting in impaired oxygenation (7). On the other hand, it has been shown that preserved spontaneous breathing during mechanical ventilation may improve ventilation-perfusion match, cardiac output, and blood pressure (8). Furthermore, synchronizing ventilator breaths with the patient's own respiratory effort may increase the efficiency of mechanical ventilation (9), improve oxygenation (10), and may decrease the incidence of chronic lung disease in neonates (11). More recently, it has been shown that assisted modes of ventilation may be combined with PLV to support spontaneously breathing animals without lung dis-

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Section: Discussionmentioning

confidence: 99%

Spontaneous Breathing during Partial Liquid Ventilation in Animals with Meconium Aspiration

et al. 2001

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“…Using electron microscopy, Bae et al (39) noticed that incubation of Survanta with meconium resulted in a transformation from loosely stacked layers, representing active surfactant, to lamellar or folded linear structures representing inactivated material. These findings are reminiscent of the conversion of the highly surface-active subtype of large surfactant aggregates to small aggregates with poor surface activity observed in adults with ARDS (40).…”

Section: Discussionmentioning

confidence: 99%

Resistance of Different Surfactant Preparations to Inactivation by Meconium

et al. 2001

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A disease similar to acute respiratory distress syndrome may occur in neonates after aspiration of meconium. The aim of the study was to compare the inhibitory effects of human meconium on the following surfactant preparations suspended at a concentration of 2.5 mg/mL: Curosurf, Alveofact, Survanta, Exosurf, Pumactant, rabbit natural surfactant from bronchoalveolar lavage, and two synthetic surfactants based on recombinant surfactant protein-C (Venticute) or a leucine/lysine polypeptide. Minimum surface tension, determined with a pulsating bubble surfactometer, was increased Ͼ10 mN/m at meconium concentrations Ն0.04 mg/mL for Curosurf, Alveofact, or Survanta, Ն0.32 mg/mL for recombinant surfactant protein-C, Ն1.25 mg/mL for leucine/lysine polypeptide, and Ն20 mg/mL for rabbit natural surfactant. The protein-free synthetic surfactants Exosurf and Pumactant did not reach minimum surface tension Ͻ10 mN/m even in the absence of meconium. We conclude that surfactant activity is inhibited by meconium in a dose-dependent manner. Recombinant surfactant protein-C and leucine/lysine polypeptide surfactant were more resistant to inhibition than the modified natural surfactants Curosurf, Alveofact, or Survanta but less resistant than natural lavage surfactant containing surfactant protein-A. We speculate that recombinant hydrophobic surfactant proteins or synthetic analogs of these proteins can be used for the design of new surfactant preparations that are relatively resistant to inactivation and therefore suitable for treatment of acute respiratory distress syndrome. Surfactant deficiency has been recognized as the cause of RDS in premature infants, and treatment with modified natural surfactant preparations has considerably improved the prognosis of this disease (1). However, it has been realized that secondary surfactant deficiency caused by inactivation of the surfactant system may occur in patients with mature lungs. In ARDS (acute (adult) RDS), surfactant inhibitors may reach the alveolar space by inhalation or aspiration, and proteins such as albumin or fibrinogen may leak into the airways as a consequence of increased vascular permeability caused by pneumonia, for example (2-4). To treat ARDS in such a patient, relatively large doses of surfactant need to be instilled to overcome the amount of surfactant inhibitors present in the airways (5). Thus, surfactant preparations used for treatment of ARDS should be relatively resistant to inactivation (6). Recent advances in the synthesis and heterologous expression of lung SPs or their analogs might allow the production of designer surfactants (7) that are highly resistant to surfactant inhibitors. Under ARDS-like conditions, such preparations may be superior to currently available modified natural surfactants.Aspiration of meconium can result in severe respiratory failure in term neonates (8 -10). Surfactant inactivation is believed to play a key role in the pathophysiology of MAS, and inhibition of the surface tension-lowering activity of surfactant by meconium has been...

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“…Further suctioning was performed if there was evidence of residual meconium-stained fluid when the oxygen saturation returned to higher than 80%. Curosurf (product of Chiesi Farmaceutici, S.p.A, Parma, Italy, and manufactured for Dey laboratories, Napa, CA); Surfacten (product of Mitsubishi Pharma, Osaka, Japan); Surfactant-TA (product of Tokyo-Tanabe Co. Ltd., Tokyo, Japan); Survanta (product of Abbott Laboratories, Abbott Park, IL); KL 4 -Surfactant (product of Johnson and Johnson Company, Raritan, NJ).…”

Section: Methodsmentioning

confidence: 99%

Effective Lavage Volume of Diluted Surfactant Improves the Outcome of Meconium Aspiration Syndrome in Newborn Piglets

2009

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Meconium aspiration syndrome (MAS) is one of the top causes of severe respiratory failure in neonates. This study was designed to investigate the effective volume of therapeutic bronchoalveolar lavage (BAL) with diluted surfactant in the treatment of MAS in newborn piglets. Human meconium was instilled in 24 piglets to induce MAS, and the piglets were randomly divided into four groups: 1) control, no lavage; 2) lavage-10, BAL with diluted surfactant (5 mg/mL, Survanta) 10 mL/kg in two aliquots; 3) lavage-20, 20 mL/kg in two aliquots; 4) lavage-30, 30 mL/kg in two aliquots. Cardiopulmonary parameters were monitored, and the lung tissue was histologically examined after experiments. The changes in oxygenation and lung compliance of lavage-20 and lavage-30 groups were significantly better than control and lavage-10 groups (p Ͻ 0.05), but there was no significant difference between lavage-20 and lavage-30 groups. The lung injury scores were significantly lower in the dependent site of lavage-20 and lavage-30 groups than the other two groups. In conclusion, using 20 mL/kg diluted surfactant in two aliquots to perform therapeutic BAL was as effective as 30 mL/kg in improving the pathophysiological outcomes in MAS and may warrant consideration clinically in treating MAS. Despite improvement in immediate resuscitation at birth and the use of assisted ventilation, respiratory distress caused by aspirated meconium is difficult to manage. Even with innovative respiratory care, some neonates with severe MAS may become candidates for extracorporeal membrane oxygenation and high rates of mortality may occur (1-3).The mechanisms in pathogenesis of MAS typically includes local obstruction of the airway by meconium debris, with associated impairment of gas diffusion, patchy atelectasis, pulmonary vascular hypertension, pulmonary inflammation, chemical pneumonitis, and surfactant inactivity (4 -10). Bolus surfactant administration has been tested for the treatment of MAS previously, but no significant reduction in mortality and other morbidities was obtained (11)(12)(13)(14).Effective meconium removal without inactivating or washing out surfactant is a potential additional treatment for treating MAS. Theoretically, the concept of therapeutic bronchoalveolar lavage (BAL) involves dilution and removal of the meconium from the airspaces. Intervention to treat progressive MAS using BAL with saline has not proved to be clinically useful (15,16) and may even be detrimental as the volume of saline can further impede gas exchange and worsen lung mechanics. Some authors have tried to use bolus surfactant given after saline lavage (15,(17)(18)(19)(20), but the surfactant distribution was not uniformly obtained in the same manner as when using surfactant lavage (21,22).Recently, technique of therapeutic BAL with diluted exogenous surfactant has been tried and shown some promising benefits in improving pathophysiological responses, increasing meconium removal amount, lowering ventilation duration, and decreasing the severity of ill...

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Morphology and Function of Pulmonary Surfactant Inhibited by Meconium

Cited by 67 publications

References 23 publications

Spontaneous Breathing during Partial Liquid Ventilation in Animals with Meconium Aspiration

Spontaneous Breathing during Partial Liquid Ventilation in Animals with Meconium Aspiration

Resistance of Different Surfactant Preparations to Inactivation by Meconium

Effective Lavage Volume of Diluted Surfactant Improves the Outcome of Meconium Aspiration Syndrome in Newborn Piglets

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