TY - JOUR
T1 - Mechanical ventilation during experimental sepsis increases deposition of advanced glycation end products and myocardial inflammation
AU - Kneyber, Martin C. J.
AU - Gazendam, Roel P.
AU - Niessen, Hans W. M.
AU - Kuiper, Jan-Willem
AU - Dos Santos, Claudia C.
AU - Slutsky, Arthur S.
AU - Plötz, Frans B.
AU - Kneijber, M.C.J.
PY - 2009/6/9
Y1 - 2009/6/9
N2 - 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. © 2009 Kneyber et al.; licensee BioMed Central Ltd.
AB - 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. © 2009 Kneyber et al.; licensee BioMed Central Ltd.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67649716613&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/19508707
U2 - https://doi.org/10.1186/cc7911
DO - https://doi.org/10.1186/cc7911
M3 - Article
C2 - 19508707
SN - 1364-8535
VL - 13
JO - Critical Care
JF - Critical Care
IS - 3
M1 - R87
ER -