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

Lonneke Smeding, Jan Willem Kuiper, Frans B. Plotz, Martin C. J. Kneyber, A. B. Johan Groeneveld*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

11 Citaten (Scopus)
157 Downloads (Pure)


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 (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 Ca2+ 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 Ca2+ exposure ex vivo decreased by LPS. High V-t ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ 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 Ca2+ handling and sensitivity.

Originele taal-2English
Aantal pagina's9
TijdschriftRespiratory Research
StatusPublished - 18-sep-2013

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