Mechanical ventilation during experimental sepsis increases deposition of advanced glycation end products and myocardial inflammation.

Crit Care. 2009 Jun 9; 13(3): R87Kneyber MC, Gazendam RP, Niessen HW, Kuiper JW, Dos Santos CC, Slutsky AS, Plotz FBABSTRACT: INTRODUCTION: Increasing evidence links advanced glycation end (AGE) products, including N(epsilon)-(carboxymethyl)lysine (CML), to the development of heart failure. Accumulation of AGE products 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 4 hrs 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) twenty-four hours after the induction of sepsis. Eight rats served as septic, non-ventilated controls and eight as non-septic, non-ventilated controls. After 28 hrs 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 to 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 to 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 to non-ventilated septic controls that was augmented by mechanical ventilation, 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 mechanical ventilation, irrespective of the ventilatory strategy.