Endothelial and Microcirculatory Function and Dysfunction in Sepsis

Abstract

SYNOPSISThe microcirculation is a series of arterioles, capillaries, and venules that performs essential functions of oxygen and nutrient delivery, customized to the unique physiologic needs of the supplied organ. The homeostatic microcirculatory response to infection, which includes barrier hyperpermeability, leukocyte adhesion, and coagulation activation, can become harmful if overactive and/or dysregulated, contributing to the organ failure characteristic of sepsis. In humans, pathologic microcirculatory dysfunction can be directly visualized by intravital microscopy or indirectly measured via detection of circulating biomarkers, such as endothelial glycocalyx fragments. While several treatments have been shown to protect the microcirculation during sepsis, these therapies have not improved patient outcomes when applied indiscriminately. Future outcomes-oriented studies are needed to test the utility of sepsis therapeutics when applied in a manner "personalized" to a patient's microcirculatory dysfunction.

Fibroblast Growth Factor Signaling Mediates Pulmonary Endothelial Glycocalyx Reconstitution

“…In human diseases characterized by ESL degradation, HS fragments are released into the circulation (22). We previously observed (8) that these plasma HS fragments include hexasaccharides to octasaccharides (degree of polymerization [dp] 6 to dp8) as well as larger-weight fractions, with high degrees of glucosamine amino-sulfation (N-sulfated, Figure 4A).…”

Coenzyme Q10 improves the survival and reduces inflammatory markers in septic patients

“…The recent researches in sepsis are focusing on two separate mechanism. The fi rst is the role of the microcirculation in the body and the mixed response of various circulatory beds to sepsis (36)(37)(38). The second is that the cells and mitochondria receiving adequate perfusion and oxygenation may still have a decreased ability to properly utilize energy to form ATP, referred to as cytopenic hypoxia, which can lead to profound metabolic alterations and the ability to supply energy to the tissues.…”

Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome

“…Damage to the alveolar-capillary barrier can be further fueled by alterations to microvascular endothelial cells and through formation of microthrombi. Injury to the endothelial cell surface, through alteration of the glycocalyx, formation of platelet-leukocyte aggregates, and triggered release of inflammatory mediators, can also facilitate loss of alveolar-capillary barrier function (31)(32)(33). Thus, in contrast with direct lung injury, pathways downstream of endothelial injury (discussed below) may be disproportionately activated following indirect lung injury.…”