Microcirculation : the official journal of the Microcirculatory Society, Inc
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Although long recognized in microvascular research, an increasing body of evidence suggests that inflammatory markers are present in human diseases. Since the inflammatory cascade serves as a repair mechanism, the presence of inflammatory markers in patient groups has raised an important question about the mechanisms that initiate the inflammatory cascade (i.e., the mechanisms that cause tissue injury). Using a severe form of inflammation, shock, and multiorgan failure, for which there is no accepted injury mechanism, we summarize studies that suggest that the powerful pancreatic digestive enzymes play a central role in the destruction of the intestine and other tissues if their compartmentalization in the lumen of the intestine and in the pancreas is compromised. ⋯ For example, in a model of metabolic disease with type II diabetes, proteolytic cleavage of the insulin receptor causes the inability of insulin to signal glucose transport across membranes. The evidence suggests that uncontrolled proteolytic and lipolytic enzyme activity may trigger the mechanism for tissue injury. The significance of such mechanisms remain to be explored in human diseases.
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As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. ⋯ Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.
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Oxygen and other substrates, waste products, hormone messengers, and cells and other particles of the immune system are all transported in a closed-loop circulatory system in vertebrates, within which pumped blood travels to within diffusion distances of practically every cell in the body. Exchange of oxygen and carbon dioxide in the pulmonary capillaries and absorption of nutrients in the gut provide the circulating blood with biochemical reactants to sustain bioenergetic processes throughout the body. ⋯ Indeed, the microcirculation is the key system that ties processes at the whole-body level of the cardiovascular system to subcellular phenomena. This tight integration between cellular metabolism and microcirculatory transport begs for integrative simulations that span the cell, tissue, and organ scales.
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Increased morbidity and mortality in critically ill obese patients may result from an exaggerated inflammatory response and/or a diminished effectiveness of routine therapeutic strategies used in the critical care setting. The objectives of this study were to compare the effectiveness of hypertonic saline (HTS) resuscitation in obese and lean mice with sepsis and to address potential mechanisms underlying HTS-mediated protection against the inflammatory and microvascular responses to sepsis. ⋯ HTS exerts significant anti-inflammatory and anti-thrombogenic actions in obese septic mice. These responses may be related to the inhibitory effect of HTS on sepsis-induced P-selectin expression.
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Increased endothelial permeability is the hallmark of inflammatory vascular edema. Inflammatory mediators that bind to heptahelical G protein-coupled receptors trigger increased endothelial permeability by increasing the intracellular Ca2+ concentration ([Ca2+]i). The rise in [Ca2+]i activates key signaling pathways that mediate cytoskeletal reorganization (through myosin-light-chain-dependent contraction) and the disassembly of VE-cadherin at the adherens junctions. ⋯ In addition, TRPC4-/- mouse-lung endothelial cells exhibited lack of actin-stress fiber formation and cell retraction in response to thrombin activation of protease-activated receptor-1 (PAR-1) in endothelial cells. The increase in lung microvascular permeability in response to PAR-1 activation was inhibited in TRPC4-/- mice. These results indicate that endothelial TRP channels such as TRPC1 and TRPC4 play an important role in signaling agonist-induced increases in endothelial permeability.