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

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 (Ca(2+))-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 (V(t)) of 6 mL/kg and 5 cmH(2)O positive end-expiratory pressure (PEEP)) or injurious ventilation (high V(t) of 19 mL/kg and 1 cmH(2)O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca(2+) exposure. Key mediators were determined in lung and heart at the mRNA level. RESULTS: Instillation of LPS and high V(t) 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 V(t) 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/dt(max) and contractile responses to increasing Ca(2+) exposure ex vivo decreased by LPS. High V(t) ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca(2+) responses. CONCLUSIONS: Injurious MV by high V(t) 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 Ca(2+) handling and sensitivity.