title: Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats.
abstract: 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.
  
  
  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.
authors.affiliation: Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, Netherlands. a.b.j.groeneveld@erasmusmc.nl.
authors.forename: Lonneke
authors.initials: L
authors.lastname: Smeding
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Kuiper
authors.forename: Frans B
authors.initials: FB
authors.lastname: Plötz
authors.forename: Martin Cj
authors.initials: MC
authors.lastname: Kneyber
authors.forename: Ab Johan
authors.initials: AJ
authors.lastname: Groeneveld
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2
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