Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis

2002 ◽  
Vol 282 (1) ◽  
pp. H156-H164 ◽  
Author(s):  
Christopher G. Ellis ◽  
Ryon M. Bateman ◽  
Michael D. Sharpe ◽  
William J. Sibbald ◽  
Ravi Gill

Inherent in the remote organ injury caused by sepsis is a profound maldistribution of microvascular blood flow. Using a 24-h rat cecal ligation and perforation model of sepsis, we studied O2 transport in individual capillaries of the extensor digitorum longus (EDL) skeletal muscle. We hypothesized that erythrocyte O2 saturation (So 2) levels within normally flowing capillaries would provide evidence of either a mitochondrial failure (increased So 2) or an O2 transport derangement (decreased So 2). Using a spectrophotometric functional imaging system, we found that sepsis caused 1) an increase in stopped flow capillaries (from 10 to 38%, P < 0.05), 2) an increase in the proportion of fast-flow to normal-flow capillaries ( P< 0.05), and 3) a decrease in capillary venular-end So 2 levels from 58.4 ± 20.0 to 38.5 ± 21.2%, whereas capillary arteriolar-end So 2levels remained unchanged compared with the sham group. Capillary O2 extraction increased threefold ( P < 0.05) and was directly related to the degree of stopped flow in the EDL. Thus impaired O2 transport in early stage sepsis is likely the result of a microcirculatory dysfunction.

1996 ◽  
Vol 270 (4) ◽  
pp. H1294-H1302 ◽  
Author(s):  
P. Wang ◽  
Z. F. Ba ◽  
S. S. Reich ◽  
M. Zhou ◽  
K. R. Holme ◽  
...  

Although heparinization of animals before hemorrhage improves cell and organ function, the potent anticoagulant activity of conventional heparin sodium precludes its potential clinical use. To determine whether a novel nonanticoagulant heparin, GM1892, would have any beneficial effects on cardiovascular and hapatocellular functions and would decrease susceptibility to sepsis after hemorrhage, laparotomy was performed on rats (i.e., trauma induced), after which they were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleedout volume was returned in the form of Ringer lactate solution (RL). The rats were then resuscitated with three times the volume of shed blood with RL over 45 min, followed by infusion of two times RL plus GM1892 (7 mg/kg body wt; approximately 2% the anticoagulant activity of regular heparin) of saline over 60 min. At 2 and 4 h after the completion of resuscitation, cardiac output, hepatocellular function, and microvascular blood flow were determined. The results indicated that cardiac output, hepatocellular function, and microvascular blood flow in the liver, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Administration of GM1892, however, restored these parameters. The morphological abnormality observed after hemorrhage in the liver, kidney, and small gut was also attenuated with GM1892 treatment. Moreover, GM1892 normalized the elevated plasma prostaglandin E2 levels. Sepsis was induced in additional rats by cecal ligation and puncture (CLP) 20 h after hemorrhage, and the necrotic cecum was excised 10 h thereafter. GM1892 treatment significantly decreased mortality after CLP and cecal excision. Thus GM1892 appears to be a useful adjunct to fluid resuscitation, since it restores the depressed cardiovascular responses and decreases susceptibility to sepsis after trauma and hemorrhage.


1992 ◽  
Vol 263 (1) ◽  
pp. G38-G43 ◽  
Author(s):  
P. Wang ◽  
M. Zhou ◽  
M. W. Rana ◽  
Z. F. Ba ◽  
I. H. Chaudry

Although cellular dysfunction occurs very early in sepsis, it remains controversial whether this is solely due to a decrease in tissue perfusion. Recent studies have indicated that while active hepatocellular function was depressed, hepatic surface microvascular blood flow (MBF) increased in early sepsis but decreased in late sepsis as produced by cecal ligation and puncture (CLP). However, it is not known whether microvascular hyperperfusion in early sepsis and microvascular hypoperfusion in late sepsis are common events in other organs under such conditions. To study this, rats were subjected to sepsis by CLP, after which these and the corresponding shams received 3 ml/100 g body wt normal saline. Microvascular perfusion and MBF in various tissues were assessed by colloidal carbon infusion and laser-Doppler flowmetry, respectively, at 5 h (i.e., early sepsis) or 20 h (late sepsis) after CLP or sham operation. Carbon-perfused areas were quantitated by an Optomax image analyzer. The results indicate that the carbon-perfused areas and MBF in the liver, renal cortex, spleen, and small intestinal serosa (only MBF) increased significantly 5 h after CLP. In late sepsis, however, the carbon-perfused areas and MBF were found to be significantly decreased. A highly linear relationship was observed between the changes of carbon-perfused areas and MBF during sepsis in the tested organs. Thus the microvascular responses in the fluid-resuscitated sepsis model are characterized by hyperperfusion in the early stage and hypoperfusion in the late stage of sepsis in the tested tissues. The cellular dysfunctions observed during the early stage of sepsis are, therefore, not due to any reduction in tissue perfusion.


2007 ◽  
Vol 141 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Aysen Erdem ◽  
A. Meltem Sevgili ◽  
Filiz Akbiyik ◽  
Pergin Atilla ◽  
Nur Cakar ◽  
...  

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
B. G. H. Janssen ◽  
Y. M. Zhang ◽  
I. Kosik ◽  
A. Akbari ◽  
C. W. McIntyre

AbstractHemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1715-P
Author(s):  
KATHERINE ROBERTS-THOMSON ◽  
RYAN D. RUSSELL ◽  
DONGHUA HU ◽  
TIMOTHY M. GREENAWAY ◽  
ANDREW C. BETIK ◽  
...  

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