Disturbances of surfactant activity and possibilities its correction in acute lung lesions

Special studies have shown surfactant activity disorders in the development of acute lung injuries, such as shock lung, respiratory distress syndrome (RDS), pneumonia, which plays an essential role in the development and severity of disease [1]. Surfactant, reducing the surface tension in the alveoli and thereby ensuring their stability on the exhale, and reduces the hydrostatic pressure in the pulmonary capillaries, preventing transudation of fluid fr om them [2]. Thus, the lack of surfactant leads to both atelectasis and pulmonary edema. The main active principle is a surfactant dipalmitoyl phosphatidyl choline, but there are protein components thereof, that is the surfactant is a lipoprotein synthesis that occurs in type II alveolocytes.

There are several attempts to explain the decrease in the activity of surfactant. In particular, it is believed that the protein and the liquid entering the alveolus edema, disrupt the surfactant layer, wash it. And possible direct inhibition of surfactant under the influence of some toxic substances, among which are there fatty acids. Histochemical studies have shown that within 15 minutes after intravenous injection of oleic acid changes occur of surface-active film alveoli, its fragmentation. And there is direct evidence that the septic complications increases the level of free fatty acids, is directly correlated with mortality. Suppress the activity of the surfactant with the development of RDS may increase levels of endotoxin in the blood [3, 4].

All this was the basis for the use of exogenous surfactant in the treatment of RDS [5]. However, voices were heard and the inability of exogenous surfactant to correct respiratory failure with RDS, especially in adults [6, 7]. However, the use of surfactant in infants proved more rapid decline in FiO2 to 40% and reducing the length of mechanical ventilation, but to increase survival to 7 and 28 days has not been reached [8]. A.V.Vlasenko et al. [9] also noted that the use of surfactant dave only a temporary effect. This reduces the duration of mechanical ventilation and length of stay in the ICU, but significant reduction in mortality not occurred.

The aim of this work was to determine the causes of violations of surfactant activity and possibilities of their correction in patients with RDS.  

Studying surfactant activity was conducted according to the procedure J.A.Clements [10] (A.F.Ovchinin). To 3 g of lung tissue minced with scissors and extracted surfactant in 50 ml isotonic sodium chloride solution. After 30 minutes of exposure with constant agitation extract was placed in a special cell with a fortified movable barrier. The area of the cell smoothly or tiers could be reduced from 100 to 20%, making it possible to record the hysteresis loop of the surface tension, which was measured by a quartz plate retracting force on the balance of Wilhelmy-Longmure.
Was the most informative while reducing the surface tension of the cell area to 20% (corresponding to the expiration of the lungs), reflecting the highest possible activity of surfactant in the extract or “minimal surface tension”. In the description below, the results of research, the term “surface tension” is meant “the minimum surface tension”, expressed in dyne/cm (mN/m).

Surfactant activity was determined by measuring the surface tension of lung extracts obtained from 12 patients who died with symptoms of RDS because of acute pneumonia and infectious lung destruction.

Activity standard for surface tension took pieces of lung tissue of 20 healthy dogs that under intratracheal anesthesia, thoracotomy was performed and the subsequent experiments, unrelated to the current tasks.

To elucidate the causes of impaired surfactant activity that was excluded influence the whole organism were special experiments in vitro, when to the extracts  of dog lungs were added to 10 ml of blood from healthy dogs (5), healthy donors (5) or 10 patients suffering from acute lung injury (RDS, pneumonia, abscess or gangrene of the lungs).

Surface tension of lung extracts of healthy dogs averaged 5.2±0.7, wile in patients it was 20.29±1.6 dynes/cm. However, a closer examination reveals that the surface tension in the extracts of the modified areas of the lung with their “hepatization” (most of posterolateral their departments) reached 27.37±3.2 dyne/cm. At the same time, the tissue with symptoms of edema, but still the  aerial (in the upper front of the lungs), the surface tension was only 14.41±1.29 dynes/cm. Even more pronounced this difference is visible in Fig. 1, which shows the hysteresis loop of the surface activity of extracts of lung tissue from the lower and upper lobe  of the right lung patient K., 33 years.

In in vitro experiments, was originally established the absence of any inhibitory effect on the activity of the surfactant blood of healthy humans and animals (blood donors). At the same time, the addition of blood of sick people surfactant activity significantly inhibited

  More clearly it is presented in Fig. 2, which shows the effect of adding to the extract dog long blood of the same patient K.

  This difference of surfactant activity in different parts of the lungs could depend on it more inhibition in the place wh ere  the maximum yield in the alveoli of toxic components of blood plasma in toxic pulmonary edema.
Possibility of direct inhibition of surfactant some substances circulating in the blood, at first view, it may seen unlikely, since the surfactant lining the alveoli inside, protected from the effects of these substances alveolar-capillary membrane. However, with the development of  RDS permeability of the membrane is broken, and that allows it to penetrate into the alveolus with edematous fluid and thus toxic substances. In this case, and their possible direct contact with surfactant.
This was confirmed by experiments carried out earlier modeling RDS in animals [11]. The findings showed that RDS is a consequence of endotoxemia. And it is based on toxic pulmonary edema.  Proof toxic nature of RDS was the basis for its treatment tactics developed using various methods of detoxification – hemoadsorption and plasma exchange [12].      Even when the extracorporeal membrane oxygenation (ECMO), the main effect is the sorption column perfusion circuit. At the same time, even against the background of almost total destruction of the lungs, after 8-10 hours of light airiness observed recovery, and their almost complete normalization was achieved in 24-36 hours ECMO. At the same time when using only ECMO but without detoxification, to achieve the same effect required two weeks. On the other hand, through detoxification, without resorting to ECMO and even the introduction of surfactant, managed to reduce mortality in severe RDS from 74 to 31% [12].

Exactly the same positive effect gave the use of detoxification (membrane plasmapheresis), with respiratory distress syndrome in neonates, including very preterm and weighing up to 700g, which is considered a major deficiency of surfactant mechanism of pathogenesis of pulmonary lesions. At the same time without any additional surfactant is also a few hours on radiographs showed regeneration of airiness lungs [13].

Thus, no satisfactory results of use of surfactant, on the one hand, and achieving much better results when using detoxification methods in RDS, on the other hand, suggests that the true cause of the fall of surfactant activity is its inhibition of toxic substances penetrating into the alveolus at toxic violation of vascular permeability. Thus introduced exogenous surfactant, as well as natural and falls under the effect of these toxic substances, and their activity ceases.
Using detoxification contributes to the elimination of porosity vascular pathogenetic is more reasonable treatment of RDS, as after the termination proceeds into the alveolus of toxic substances in the coming hours restored reproduction of natural surfactant, which eliminates the need for its introduction of exogenous drugs.

This also applies to cases of of RDS in premature infants who do have a deficiency of surfactant, but most often develops ok RDS “adult” type – as toxic pulmonary edema as a result of entering of mothers endotoxins into the bloodstream of the fetus when the mother disorders of pregnancy, which caused a preterm birth.  Therefore, such a newborn justified the use of detoxification – a specially designed syringe membrane plasmapheresis method [14], after which there is no need in additional administration of exogenous surfactant.

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