Cellular dysoxia

Inherent in the inflammatory response to sepsis is abnormal microvascular perfusion. Maldistribution of capillary red blood cell (RBC) flow in rat skeletal muscle has been characterized by increased 1) stopped-flow capillaries, 2) capillary oxygen extraction, and 3) ratio of fast-flow to normal-flow capillaries. On the basis of experimental data for functional capillary density (FCD), RBC velocity, and hemoglobin O2 saturation during sepsis, a mathematical model was used to calculate tissue O2 consumption (Vo2), tissue Po2 (Pt) profiles, and O2 delivery by fast-flow capillaries, which could not be measured experimentally...

For much of the 20th century, lactate was largely considered a dead-end waste product of glycolysis due to hypoxia, the primary cause of the O2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis-induced tissue damage. Since the 1970s, a 'lactate revolution' has occurred. At present, we are in the midst of a lactate shuttle era; the lactate paradigm has shifted. It now appears that increased lactate production and concentration as a result of anoxia or dysoxia are often the exception rather than the rule...

A two-compartment mass transport model of tissue CO(2) exchange is developed to examine the relative contributions of blood flow and cellular hypoxia (dysoxia) to increases in tissue and venous blood CO(2) concentration. The model assumes perfectly mixed homogeneous conditions, steady-state equilibrium, and CO(2) production occurring exclusively at the tissues. The behavior of the model is compared with published data derived from an isolated dog hindlimb preparation subjected to either reductions in blood flow (ischemic hypoxia) or decreases in arterial PO(2) (hypoxic hypoxia)...

Sepsis is an increasingly common problem, particularly among critically ill patients. Mechanisms by which sepsis induces organ dysfunction have not been elucidated. The coexisting findings (unique to sepsis) of metabolic acidosis yet increased tissue oxygen tensions suggest cellular availability but decreased use of oxygen (tissue dysoxia). Because mitochondria use more than 90% of total body oxygen consumption for adenosine triphosphate (ATP) generation, a bioenergetic abnormality is implied. Cell and animal data have shown that nitric oxide (and its metabolites), produced in considerable excess in patients with sepsis, can affect oxidative phosphorylation by inhibiting several of its component respiratory enzymes...

Changes in red blood cell (RBC) function can contribute to alterations in microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and neutrophil deformability impair the passage of these cells through the microcirculation. While the role of leukocytes has been the focus of many studies in sepsis, the role of erythrocyte rheological alterations in this syndrome has only recently been investigated. RBC rheology can be influenced by many factors, including alterations in intracellular calcium and adenosine triphosphate (ATP) concentrations, the effects of nitric oxide, a decrease in some RBC membrane components such as sialic acid, and an increase in others such as 2,3 diphosphoglycerate...

An estimated 750,000 cases of severe sepsis occur annually in the United States, and the mortality rate is about 30%. As a condition that disproportionately affects the elderly and is related to invasive and immunosuppressive healthcare, increases in the frequency of sepsis are anticipated. The complex pathophysiology of sepsis encompasses the interplay of pro- and anti-inflammatory mediators, activated circulating and resident inflammatory cells, disrupted coagulation, endothelial activation and injury, vasodilatation and vascular hyporesponsiveness to vasoactive mediators, cardiac dysfunction, and cellular dysoxia...

A simple mathematical model of electron flow along the mitochondrial respiratory cytochrome assembly and the transfer of electrons to molecular oxygen is presented. First, an expression for the current-voltage relationship for a biological oxygen electrode is derived, and from this the relationship between oxygen consumption rate and oxygen partial pressure is determined. An independent relationship between mitochondrial oxygen partial pressure and oxygen supply rate is then derived. By eliminating oxygen partial pressure from these two expressions, we may obtain a relationship between oxygen supply rate and oxygen consumption rate...

OBJECTIVE: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early reperfusion in pigs. DESIGN: Descriptive study. SETTING: University hospital research laboratory. ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (DO2) were both calculated using standard formulae...

OBJECTIVE: Mitochondrial cytochrome a,a3 redox shifts can be determined by near-infrared wavelength reflection. Since near-infrared wavelengths penetrate skin and bone, a potential exists to noninvasively measure mitochondrial oxidation using this phenomenon. The purpose of this study was to compare conventional parameters of resuscitation with regional measurements of spectroscopically derived cytochrome redox state in a hemorrhagic shock model. DESIGN: Prospective, controlled laboratory investigation...

Current monitoring of critically ill patients uses measurement of global parameters such as oxygen consumption and lactate levels. With development of new monitoring technologies, it may be possible to monitor patients on an organ or tissue level, allowing manipulation of specific organ or tissue perfusion. Potentially useful techniques for monitoring tissue energetics in the future include NIR and NMR spectroscopy. However, both of these techniques are currently limited in their usefulness due to technical factors; NIR by its inability to monitor "silent" metabolically active organs and NMR by its cost, size, and interference of magnetic fields with electronic equipment...

The acute toxicity of cyanide is largely due to the inhibition of cytochrome oxidase, and the subsequent breakdown of cellular metabolism. Breakdown in cellular metabolism, leading to a disruption of cellular integrity lies at the heart of the permanent neurological damage resulting from ischemic/hypoxic brain insult. In 200 g male Wistar rats treated with 5 mg/kg KCN i.v. and ventilated until spontaneous breathing restarted, the cornea reflex, tail-pinch reaction and righting reflex disappeared for about 20 min...