Long-term severe sepsis/septic shock was associated with greater interstitial macrophage infiltration, TNF-alpha expression, lipid accumulation, and actin/myosin disruption compared to controls.
Observational (n=19)
Does long-term severe sepsis/septic shock cause myocardial structural changes that could lead to cardiac dysfunction?
Long-term severe sepsis induces significant myocardial structural and immunohistochemical changes, including oxidative damage and inflammation, which may be responsible for sepsis-induced cardiac dysfunction.
The present investigation sought to determine the cellular mechanisms directly dependent on long-term severe sepsis/septic shock that could lead to myocardial structural changes in humans. Human hearts from eight cases of long-term severe sepsis/septic shock arising from infection, as defined by the ACCP/SCCM Consensus Conference; eight cases of acute necrotizing pancreatitis and acute lung injury, a noninfectious pathologic cause of systemic inflammatory response; and three cases of accidental death without thoracic injury selected from autopsies were studied. Transmural blocks of myocardial tissue were excised from the middle portion of the left ventricular free wall and were fixed in formalin or were frozen. Histochemical and immunohistochemical methods were used to evaluate the cross-striations of the myocardial cells, the number and size of interstitial macrophages, the intracardiomyocyte accumulation of lipid, the actin/myosin contractile apparatus, and the expression of iNOS, nitrotyrosine, and TNF-alpha in the myocardia of septic and control hearts. Greater interstitial cellular infiltration composed of larger and elongated macrophages and TNF-alpha protein expression in myofibers, interstitial macrophage cell types, and smooth muscle cells and endothelial cell in the vessels; intracardiomyocyte lipid accumulation; scattered foci of actin/myosin contractile apparatus disruption; and increased expression for iNOS and nitrotyrosine in myocytes and interstitial macrophage cell types could be observed in long-term human septic myocardium as compared with normal and acute pancreatitis control myocardia. These findings give support to an opinion that structural changes could be responsible for long-term sepsis-induced myocardial dysfunction. The higher number of macrophages, most of them with morphological features of "activation," and TNF-alpha protein expression could favor the reduction of cardiac function in septic hearts. The intramyocyte lipid accumulation in these hearts very likely reflects myocardium ventricular contractile dysfunction. In addition, the increased expression of iNOS and the evidence for the significant presence of peroxynitrite in cardiomyocytes and interstitial macrophage cell types suggest that oxidative damage may play a role in actin/myosin disruption in the hearts of septic patients.
Rossi et al. (Fri,) conducted a observational in Long-term severe sepsis/septic shock (n=19). Long-term severe sepsis/septic shock vs. Acute necrotizing pancreatitis and accidental death was evaluated on Myocardial structural changes including macrophage infiltration, lipid accumulation, and protein expression. Long-term severe sepsis/septic shock was associated with greater interstitial macrophage infiltration, TNF-alpha expression, lipid accumulation, and actin/myosin disruption compared to controls.