Abstract
BackgroundMechanical 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 methodsN = 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.ResultsInstillation 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.ConclusionsInjurious 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.
Highlights
Injurious mechanical ventilation (MV) can induce ventilator-induced lung injury (VILI) and may thereby contribute to multiple organ failure, potentially by spillover from lung-borne inflammatory mediators into the circulation which may act on distant organs such as the kidneys [1,2,3]
Instillation of LPS and high Vt Mechanical ventilation (MV) impaired gas exchange and, when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression increased by the interaction between LPS and high Vt MV
C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, left ventricular (LV) developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS
Summary
Injurious mechanical ventilation (MV) can induce ventilator-induced lung injury (VILI) and may thereby contribute to multiple organ failure, potentially by spillover from lung-borne inflammatory mediators into the circulation which may act on distant organs such as the kidneys [1,2,3]. We have shown that injurious MV (ie high tidal volume (Vt) ventilation) for 4 hours augmented myocardial inflammation in a cecal ligation and puncture model through an enhanced deposition of advanced glycation end products resulting in increased myocardial inflammation [9]. These latter studies suggest that pulmonary overdistention and VILI may induce myocardial inflammation but the functional consequences were not examined. 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
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