Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

Abstract

Background: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.

Materials and methods: N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.

Results: Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.

Conclusions: Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.

Figure 1

In vivo measurements in the course of time (LPS=lipopolysaccharide; LVt=low tidal volume (V_t) ventilation, HVt=high V_t ventilation). Mean arterial pressure (A), central venous pressure (B) and heart rate (C). Cardiac output (D) decreased by the interaction between LPS installation and HVt ventilation.

Figure 2

Ventilator-induced lung injury induction in the course of time (LPS=lipopolysaccharide; LVt=low tidal volume (V_t) ventilation, HVt=high V_t ventilation). A. pH. B. PCO₂. C. P_aO₂/F_iO₂. D. PO₂. E. Mean airway pressure. F Pulmonary wet/dry ratio increased by LPS and HVt ventilation interaction.

Figure 3

Myocardial function ex vivo (LPS=lipopolysaccharide; LVt=low tidal volume (V_t) ventilation, HVt=high V_t ventilation). A. Left ventricular (LV) systolic pressure. B. LV diastolic pressure. C. LV developed pressure decreased by the interaction between LPS installation and HVt ventilation. D. LV contractility, measured as +dP/_dtmax, decreased by the interaction between LPS installation and HVt ventilation. E. LV relaxation, measured as –dP/dt_min, decreased by the interaction between LPS installation and HVt ventilation. F. LV pCa₅₀.