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Updated: May 7, 2026
3D Cine Magnetic Resonance Imaging of Respiratory Motion in Mechanically Ventilated Mice and Rats
Published on: September 19, 2025
Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats
Lonneke Smeding1, Jan Willem Kuiper, Frans B Plötz
1Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, Netherlands. a.b.j.groeneveld@erasmusmc.nl.
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 (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.
Results:
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.
Conclusions:
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.
Insights
Mechanical ventilation with high tidal volumes worsens heart dysfunction in LPS-injured lungs, increasing inflammation via HSP70 and TLR2, not calcium pathways.
Area of Science:
- Physiology
- Pathology
- Critical Care Medicine
Background:
- Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI), potentially leading to multiple organ failure.
- Lipopolysaccharide (LPS) instillation models bacterial sepsis, inducing lung injury and systemic inflammation.
- The cardiac effects of VILI, particularly in the context of pre-existing lung injury, require further elucidation.
Purpose of the Study:
- To investigate if injurious MV of lipopolysaccharide (LPS)-pre-injured lungs induces myocardial inflammation and dysfunction.
- To determine if this effect is mediated by a calcium (Ca2+)-dependent mechanism.
Main Methods:
- Rats received LPS or saline intratracheally, followed by either lung-protective or injurious MV for 4 hours.
- Myocardial function was assessed ex vivo using a Langendorff setup with varying Ca2+ concentrations.
- Gene expression of key inflammatory mediators in lung and heart tissue was analyzed.
Main Results:
- Combined LPS and injurious MV significantly worsened gas exchange and lung injury.
- Injurious MV exacerbated LPS-induced myocardial inflammation (increased CXCL1, TLR2 mRNA) and dysfunction (reduced LV pressures and contractility).
- These cardiac effects were not dependent on altered Ca2+ handling or sensitivity.
Conclusions:
- High tidal volume injurious MV aggravates LPS-induced myocardial dysfunction.
- This aggravation is likely mediated by enhanced myocardial inflammation, involving pulmonary heat shock protein 70 (HSP70) stimulating cardiac Toll-like receptor 2 (TLR2).
- The mechanism does not appear to involve alterations in cardiac Ca2+ handling or sensitivity.
