Effects of time-controlled adaptive ventilation on cardiorespiratory parameters and inflammatory response in experimental emphysema

Abstract

The time-controlled adaptive ventilation (TCAV) method attenuates lung damage in acute respiratory distress syndrome. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury (VILI) and cardiac function in emphysema. We hypothesized that the use of the TCAV method to achieve an expiratory flow termination/expiratory peak flow (E_FT/E_PF) of 25% could reduce VILI and improve right ventricular function in elastase-induced lung emphysema in rats. Five weeks after the last intratracheal instillation of elastase, animals were anesthetized and mechanically ventilated for 1 h using TCAV adjusted to either E_FT/E_PF 25% or E_FT/E_PF 75%, the latter often applied in acute respiratory distress syndrome (ARDS). Pressure-controlled ventilation (PCV) groups with positive end-expiratory pressure levels similar to positive end-release pressure in TCAV with E_FT/E_PF 25% and E_FT/E_PF 75% were also analyzed. Echocardiography and lung ultrasonography were monitored. Lung morphometry, alveolar heterogeneity, and biological markers related to inflammation [interleukin 6 (IL-6), CINC-1], alveolar pulmonary stretch (amphiregulin), lung matrix damage [metalloproteinase 9 (MMP-9)] were assessed. E_FT/E_PF 25% reduced respiratory system peak pressure, mean linear intercept, B lines at lung ultrasonography, and increased pulmonary acceleration time/pulmonary ejection time ratio compared with E_FT/E_PF 75%. The volume fraction of mononuclear cells, neutrophils, and expression of IL-6, CINC-1, amphiregulin, and MMP-9 were lower with E_FT/E_PF 25% than with E_FT/E_PF 75%. In conclusion, TCAV with E_FT/E_PF 25%, compared with E_FT/E_PF 75%, led to less lung inflammation, hyperinflation, and pulmonary arterial hypertension, which may be a promising strategy for patients with emphysema.NEW & NOTEWORTHY The TCAV method reduces lung damage in ARDS. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury and cardiac function in experimental emphysema. The TCAV method at E_FT/E_PF ratio of 25%, compared with E_FT/E_PF of 75% (frequently used in ARDS), reduced lung inflammation, alveolar heterogeneity and hyperinflation, and pulmonary arterial hypertension in elastase-induced emphysema. TCAV may be a promising and personalized ventilation strategy for patients with emphysema.

Keywords: alveolar heterogeneity; emphysema; hyperinflation; right ventricle function; time-controlled adjusted ventilation.