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

Lonneke Smeding1234, Jan Willem Kuiper123, Frans B Plötz5, Martin CJ Kneyber1267 and AB Johan Groeneveld18*

Author Affiliations

1 Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, Netherlands

2 Department of Pediatric Intensive Care, VU University Medical Center, Amsterdam, Netherlands

3 Department of Physiology, VU University Medical Center, Amsterdam, Netherlands

4 Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands

5 Department of Pediatrics, Tergooi Hospital, Blaricum, Netherlands

6 Department of Pediatrics, Division of Pediatric Intensive Care, Beatrix Children’s Hospital/University Medical Center Groningen, The University of Groningen, Groningen, Netherlands

7 Critical Care, Anesthesiology, Peri-operative medicine and Emergency Medicine (CAPE), The University of Groningen, Groningen, Netherlands

8 Department of Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands

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Respiratory Research 2013, 14:92  doi:10.1186/1465-9921-14-92

Published: 18 September 2013



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.


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.


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.

Biotrauma; Ventilator-induced lung injury; Myocardial depression; Endotoxin; Toll like receptor (TLR)2; Chemokine (C-X-C motif) ligand (CXCL)1; Heat shock protein (HSP)70