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

Kneyber MC, Gazendam RP, Niessen HW, Kuiper JW, Dos Santos CC, Slutsky AS, Plötz FB - Crit Care (2009)

Bottom Line: 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).CML deposition was significantly correlated with the number of macrophages and PMNs in the heart.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatric Intensive Care, VU university medical center, 1007 MB Amsterdam, The Netherlands. m.c.j.kneyber@bkk.umcg.nl

ABSTRACT

Introduction: Increasing evidence links advanced glycation end products (AGE) including Nepsilon-(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.

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Immunohistochemical staining for Nε-(carboxymethyl)lysine (CML) in the left ventricular wall of a mechanically ventilated rat with sepsis. Arrows indicate positive staining of blood vessels for CML (original magnification 200×).
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Figure 1: Immunohistochemical staining for Nε-(carboxymethyl)lysine (CML) in the left ventricular wall of a mechanically ventilated rat with sepsis. Arrows indicate positive staining of blood vessels for CML (original magnification 200×).

Mentions: CML depositions were found in small intra-myocardial arteries (Figure 1). Sepsis induced a significant increase of CML intensity score in both left ventricle (LV) and right ventricle (RV), compared with non-septic controls (Figure 2). The CML intensity score in the RV was significantly higher compared with the LV (0.7 ± 0.1 vs 1.7 ± 0.2; P < 0.001). The combination of sepsis and MV significantly increased the CML intensity score in both the LV and RV compared with non-septic controls (LV 0.3 ± 0.1 vs 1.0 ± 0.1, P < 0.01; RV 0.6 ± 0.1 vs 2.5 ± 0.5, P = 0.03). There were no differences between the LTV and HTV groups in both ventricles, although in the RV there was a trend towards a higher intensity score in the HTV group compared with non-ventilated sepsis (1.0 ± 0.1 vs 0.7 ± 0.09, P = 0.07; Figure 2).


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

Kneyber MC, Gazendam RP, Niessen HW, Kuiper JW, Dos Santos CC, Slutsky AS, Plötz FB - Crit Care (2009)

Immunohistochemical staining for Nε-(carboxymethyl)lysine (CML) in the left ventricular wall of a mechanically ventilated rat with sepsis. Arrows indicate positive staining of blood vessels for CML (original magnification 200×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2717457&req=5

Figure 1: Immunohistochemical staining for Nε-(carboxymethyl)lysine (CML) in the left ventricular wall of a mechanically ventilated rat with sepsis. Arrows indicate positive staining of blood vessels for CML (original magnification 200×).
Mentions: CML depositions were found in small intra-myocardial arteries (Figure 1). Sepsis induced a significant increase of CML intensity score in both left ventricle (LV) and right ventricle (RV), compared with non-septic controls (Figure 2). The CML intensity score in the RV was significantly higher compared with the LV (0.7 ± 0.1 vs 1.7 ± 0.2; P < 0.001). The combination of sepsis and MV significantly increased the CML intensity score in both the LV and RV compared with non-septic controls (LV 0.3 ± 0.1 vs 1.0 ± 0.1, P < 0.01; RV 0.6 ± 0.1 vs 2.5 ± 0.5, P = 0.03). There were no differences between the LTV and HTV groups in both ventricles, although in the RV there was a trend towards a higher intensity score in the HTV group compared with non-ventilated sepsis (1.0 ± 0.1 vs 0.7 ± 0.09, P = 0.07; Figure 2).

Bottom Line: 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).CML deposition was significantly correlated with the number of macrophages and PMNs in the heart.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatric Intensive Care, VU university medical center, 1007 MB Amsterdam, The Netherlands. m.c.j.kneyber@bkk.umcg.nl

ABSTRACT

Introduction: Increasing evidence links advanced glycation end products (AGE) including Nepsilon-(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.

Show MeSH
Related in: MedlinePlus