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Abstract

This review examines experimental evidence that the microvascular dysfunction that occurs early in sepsis is the critical first stage in tissue hypoxia and organ failure. A functional microvasculature maintains tissue oxygenation despite limitations on oxygen delivery from blood to tissue imposed by diffusion; the density of perfused (functional) capillaries is high enough to ensure appropriate diffusion distances, and arterioles regulate the distribution of oxygen within the organ precisely to where it is needed. Key components of this regulatory system are the endothelium, which communicates and integrates signals along the microvascular network, and the erythrocytes, which directly monitor and regulate oxygen delivery. During hypovolemic shock, a functional microvasculature responds to diminish the impact of a decrease in oxygen supply on tissue perfusion. However, within hours of the onset of sepsis, a dysfunctional microcirculation is, due to a loss of functional capillary density and impaired regulation of oxygen delivery, unable to maintain capillary oxygen saturation levels and prevent the rapid onset of tissue hypoxia despite adequate oxygen supply to the organ. The mechanism(s) responsible for this dysfunctional microvasculature must be understood in order to develop appropriate management strategies for sepsis.

Preparation of a Designed Poly(trimethylene carbonate) Microvascular Network by Stereolithography

“…For a cell to survive and for an organ to function properly, adequate concentrations of oxygen are required. In healthy tissue, the supply of oxygen, as mentioned before, is ensured by the microcirculation . It is clear that to adequately function as a microvascular network and scaffold in tissue engineering, oxygen and nutrients also need to reach the cells in the developing tissues.…”

Resuscitation from hemorrhagic shock using polymerized hemoglobin compared to blood

“…Microvascular function, in terms of blood flow and functional capillaries, is essential for the maintenance of tissue viability because the microcirculation is where O 2 is delivered and metabolic byproducts are washed out (21). HBOC biophysical characteristics determine the mechanisms required to restore volume, microvascular blood flow, and O 2 delivery.…”

Prognostic value of echocardiographic and Doppler parameters in horses admitted for colic complicated by systemic inflammatory response syndrome

“…4,5,46 This hypoxia could be worsened by an impairment of auto-regulating mechanisms of microcirculation, which generates a heterogenous myocardial oxygen supply. 47 Furthermore, endotoxins disrupt calcium transfer at various sites, causing a decrease in calcium sensitivity and an unresponsiveness to ␤-adrenergic stimulation of the cardiomyocytes. 4 Other factors such as autonomic nervous system dysfunction, 5 myocardial inflammatory infiltration, 46 or a tachycardiainduced cardiomyopathy 4 may similarly contribute to myocardial depression.…”