Research
Mechanical ventilation during experimental sepsis increases deposition of advanced glycation end products and myocardial inflammation
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* Corresponding author: Martin CJ Kneyber m.c.j.kneyber@bkk.umcg.nl
1 Department of Pediatric Intensive Care, VU university medical center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
2 Institute for Cardiovascular Research (ICaR-VU), VU university medical center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
3 Beatrix Children's Hospital/University Medical Center, P.O. Box 30001, 9700 RB Groningen, The Netherlands
4 Department of Pathology, VU university medical center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
5 Department of Cardiac Surgery, VU university medical center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
6 Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8; University of Toronto, Toronto, Ontario, Canada
Critical Care 2009, 13:R87 doi:10.1186/cc7911
Published: 9 June 2009Abstract
Introduction
Increasing evidence links advanced glycation end products (AGE) including Nε-(carboxymethyl)lysine (CML) to the development of heart failure. Accumulation of AGE leads to myocardial inflammation, which is considered as one of the possible mechanisms underlying sepsis-induced cardiac dysfunction. We hypothesized that mechanical ventilation (MV) augmented sepsis-induced myocardial CML deposition and inflammation.
Methods
Sepsis was induced using a modified cecal ligation and perforation (CLP) technique in 36 male adult Sprague Dawley rats. Rats were randomized to four hours of MV with low tidal volume (LTV: 6 ml/kg, PEEP 5 cmH2O, n = 10) or high tidal volume (HTV: 15 ml/kg, PEEP 3 cmH2O, n = 10) 24 hours after the induction of sepsis. Eight rats served as septic, non-ventilated controls and eight as non-septic, non-ventilated controls. After 28 hours all rats were killed. The number of extravascular polymorphonuclear (PMN) leucocytes, macrophages, and lymphocytes was measured as the number of positive cells/mm2. The number of CML positive endothelial cells were semi-quantified based upon an intensity score. The CML intensity score was correlated with the number of inflammatory cells to study the association between CML depositions and inflammation.
Results
Gas exchange was comparable between the ventilated groups. Sepsis induced a significant increase in CML deposition in both ventricles that was significantly augmented by MV compared with non-ventilated septic controls (left ventricle 1.1 ± 1.0 vs 0.7 ± 0.1, P = 0.030; right ventricle 2.5 ± 0.5 vs 0.6 ± 0.1, P = 0.037), irrespective of ventilatory strategy. In the right ventricle there was a non-significant tendency towards increased CML deposition in the HTV group compared with septic, non-ventilated controls (1.0 ± 0.1 vs 0.7 ± 0.09, P = 0.07). Sepsis induced a significant increase in the number of macrophages and PMNs compared with non-ventilated septic controls that was augmented by MV, irrespective of ventilatory strategy. CML deposition was significantly correlated with the number of macrophages and PMNs in the heart.
Conclusions
Sepsis induces CML deposition in the heart with a predominant right ventricular inflammation that is significantly augmented by MV, irrespective of the ventilatory strategy.