Impact of ventilation-induced lung injury on the structure and function of lamellar bodies

Abstract

Alterations to the pulmonary surfactant system have been observed consistently in ventilation-induced lung injury (VILI) including composition changes and impairments in the surface tension reducing ability of the isolated extracellular surfactant. However, there is limited information about the effects of VILI on the intracellular form of surfactant, the lamellar body. It is hypothesized that VILI leads to alterations of lamellar body numbers and function. To test this hypothesis, rats were randomized to one of three groups, nonventilated controls, control ventilation, and high tidal volume ventilation (VILI). Following physiological assessment to confirm lung injury, isolated lamellar bodies were tested for surfactant function on a constrained sessile drop surfactometer. A separate cohort of animals was used to fix the lungs followed by examination of lamellar body numbers and morphology using transmission electron microscopy. The results showed an impaired ability of reducing surface tension for the lamellar bodies isolated from the VILI group as compared with the two other groups. The morphological assessment revealed that the number, and the relative area covered by, lamellar bodies were significantly decreased in animals with VILI animals as compared with the other groups. It is concluded that VILI causes significant alterations to lamellar bodies. It is speculated that increased secretion causes a depletion of lamellar bodies that cannot be compensated by de novo synthesis of surfactant in these injured lungs.

Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits

“…Milos et al found quite recently that high tidal volume ventilation (VILI) lead to significant alterations of lamellar body (LB) numbers and function . An impaired ability of reducing surface tension for the LB isolated from the VILI group was observed, the LB number and LB area was also significantly decreased, suggesting that LB changes after VILI contribute to impairments in surface tension reduction within the alveolar hypophase.…”

“…(VILI) lead to significant alterations of lamellar body (LB) numbers and function. 19 An impaired ability of reducing surface tension for the LB isolated from the VILI group was observed, the LB number and LB area was also significantly decreased, suggesting that LB changes after VILI contribute to impairments in surface tension reduction within the mice. 25 Another study showed that inhalation of BUD could significantly increase the SP-B precursors in the bronchoalveolar lavage fluids of patients with chronic lung diseases.…”

The micromechanics of lung alveoli: structure and function of surfactant and tissue components

“…Conversely, surfactant dysfunction may also be a direct consequence of abnormal alveolar micromechanics. Mechanical but also spontaneous ventilation can be associated with undue alveolar strain and large changes of the alveolar surface area which has been shown to be responsible for alterations of the intracellular and intra-alveolar surfactant system and finally acute lung injury (Milos et al 2017 ; Veldhuizen et al 2002 ; Mascheroni et al 1988 ). Mechanical ventilation with high tidal volumes to induce abnormally high strain of the lung results in a conversion of biophysically active large aggregates of surfactant to inactive small aggregates of surfactant within the airspaces (Veldhuizen et al 2002 ).…”

Fluid restriction reduces pulmonary edema in a model of acute lung injury in mechanically ventilated rats

“…In experimental animal models, the choice of intravenous fluid maintenance varies widely [9, 19–21]. For example, in rat models rates starting at 1 ml/kg/hour [9] up to 10 ml/kg/hour [11, 21] have been used, and sometimes even with volumes varying between animals within a study [11]. It is an interesting realization, that while evidence of the adverse effects of fluid overload in ARDS patients is accumulating [1, 4], fluid strategies in animal models are not already under a stricter, well-formed policy.…”

“…Given the above mentioned important influences of fluid treatment for the course of ARDS in humans it is remarkable that so far the potential effects of intravenous fluid maintenance strategies on markers of acute lung injury in animals have not been addressed. There is currently no protocol or consensus regarding a standard fluid strategy, resulting in the use of a wide range of fluid rates within models using the same animal species [9, 11]. Likewise, the potential effect of age-related differences in the response to fluids during acute lung injury remains unknown.…”