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.