Effect of nitric oxide on capillary hemodynamics and cell injury in the pancreas duringPseudomonaspneumonia-induced sepsis

2004 ◽  
Vol 286 (1) ◽  
pp. H340-H345 ◽  
Author(s):  
Barbara Tribl ◽  
Ryon M. Bateman ◽  
Stephanie Milkovich ◽  
William J. Sibbald ◽  
Christopher G. Ellis
Keyword(s):  
Nitric Oxide ◽  
Cell Injury ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Cellular Damage ◽  
Supply Rate ◽  
Injury Model ◽  
Nitrite Nitrate ◽  
Plasma Nitrite

Sepsis-induced nitric oxide (NO) overproduction has been implicated in a redistribution of flow from the pancreas making it vulnerable to ischemic injury in septic shock. To test this hypothesis in a remote injury model of normotensive sepsis, we induced Pseudomonas pneumonia in the rat and used intravital video microscopy (IVVM) of the pancreas to measure functional capillary density, capillary hemodynamics [red blood cell (RBC) velocity, lineal density, and supply rate], and lethal cellular damage (propidium iodine staining) at 6 and 24 h after the induction of pneumonia. With pneumonia, plasma nitrite/nitrate [[Formula: see text]] levels were doubled by 21 h ( P < 0.05). To assess the effect of NO overproduction on microvascular perfusion, N6-(1-iminoethyl)-l-lysine (l-NIL) was administered to maintain [Formula: see text] levels at baseline. Pneumonia did cause a decrease in RBC velocity of 23% by 6 h, but by 24 h RBC velocity and supply rate had increased relative to sham by 22 and 38%, respectively ( P < 0.05). l-NIL treatment demonstrated that this increase was due to NO overproduction. With pneumonia, there was no change in functional capillary density and only modest increases in cellular damage. We conclude that, in this normotensive pneumonia model of sepsis, NO overproduction was protective of microvascular perfusion in the pancreas.

scholarly journals Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis

2001 ◽  
Vol 280 (6) ◽  
pp. H2848-H2856 ◽  
Author(s):  
Ryon M. Bateman ◽  
Justin E. Jagger ◽  
Michael D. Sharpe ◽  
Mary L. Ellsworth ◽  
Sanjay Mehta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Cecal Ligation ◽  
Capillary Density ◽  
Erythrocyte Deformability ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Nitrite Nitrate ◽  
Plasma Nitrite ◽  
Rbc Deformability

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability ([Formula: see text]; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NOx) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NOx increased 254% ( P < 0.05), stopped flow capillaries increased 149% ( P < 0.05), and [Formula: see text] decreased 12.7% ( P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NOx, accumulation of HbNO, and decreases in both [Formula: see text]and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions

2006 ◽  
Vol 291 (5) ◽  
pp. H2445-H2452 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai
Keyword(s):  
Flow Distribution ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Arterial Blood ◽  
Chamber Model ◽  
Kidney Liver ◽  
Window Chamber

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% ( level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.

Microvascular perfusion deficits are not a prerequisite for mucosal injury in septic rats

1999 ◽  
Vol 276 (4) ◽  
pp. G933-G940 ◽  
Author(s):  
R. R. Nevière ◽  
M. L. Pitt-Hyde ◽  
R. D. Piper ◽  
W. J. Sibbald ◽  
R. F. Potter
Keyword(s):  
Cell Injury ◽  
Mucosal Injury ◽  
Endotoxin Tolerance ◽  
Capillary Density ◽  
Microvascular Perfusion ◽  
Myeloperoxidase Activity ◽  
Capillary Perfusion ◽  
Ileal Mucosa ◽  
Mucosal Permeability ◽  
Perfusion Deficits

Our major objective was to investigate whether injury to the mucosa of the small intestine occurred in a normotensive model of sepsis and whether such injury was associated with microvascular perfusion deficits. Using fluorescence intravital microscopy, we show direct evidence of cell injury within the mucosa (pneumonia 12.4 ± 2.6 cells/field, sham 2.2 ± 0.7 cells/field), whereas use of51Cr-labeled EDTA showed evidence of increased mucosal permeability (pneumonia 1.90 ± 0.67 ml · min−1 · 100 g−1; sham 0.24 ± 0.04 ml · min−1 · 100 g−1), 48 h following induction of pneumonia. Despite such injury the capillary density in the ileal mucosa and submucosa of pneumonic rats (1,027 ± 77 and 1,717 ± 86 mm2) was not significantly different compared with sham (998 ± 63 and 1,812 ± 101 mm2). However, a modest albeit significant decrease in capillary perfusion was measured in the muscularis layer of pneumonia (11.0 ± 1.3 mm) compared with sham (13.9 ± 0.63 mm) and appeared to be associated with leukocyte entrapment. Pretreatment using low doses of endotoxin to induce endotoxin tolerance not only increased muscularis capillary density but reduced the number of leukocytes trapped within the microvasculature, decreased myeloperoxidase activity within the ileum in pneumonic rats, and prevented mucosal injury. In conclusion, we have shown that pneumonia results in remote injury to the mucosa of the ileum and that such injury was not associated with concurrent mucosal perfusion deficits.

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer

Nitric Oxide ◽  
2016 ◽  
Vol 52 ◽  
pp. 21-28 ◽  
Author(s):  
A. Pavani Sowjanya ◽  
Meera Rao ◽  
Haripriya Vedantham ◽  
Basany Kalpana ◽  
Usha Rani Poli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Nitrite Nitrate ◽  
Plasma Nitrite ◽  
Inducible Nitric Oxide

scholarly journals Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance

2007 ◽  
Vol 112 (8) ◽  
pp. 429-440 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Claudia Scheuer ◽  
Rene Schramm ◽  
...  
Keyword(s):  
Capillary Flow ◽  
Age Groups ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Tissue Necrosis ◽  
Significant Difference ◽  
Ischaemic Necrosis ◽  
Increased Susceptibility ◽  
Capillary Dilation

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2±1 months), adult (10±2 months) and senescent (19±3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5±2.8 μm compared with 3.95±0.79 μm at baseline) and adult (12.1±3.1 μm compared with 3.36±0.45 μm at baseline) animals compared with senescent animals (8.5±1.7 μm compared with 3.28±0.69 μm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0±0 cm/cm2), whereas adult (11.9±13.5 cm/cm2) and, in particular, adolescent animals (58.4±33.6 cm/cm2; P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49±8% (P<0.05) and 42±8% (P<0.05) in senescent and adult animals respectively, compared with 31±6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance.

Helicobacter Pylori Infection and Migraine

Cephalalgia ◽  
2002 ◽  
Vol 22 (3) ◽  
pp. 222-225 ◽  
Author(s):  
I Ciancarelli ◽  
C Di Massimo ◽  
MG Tozzi-Ciancarelli ◽  
G De Matteis ◽  
C Marini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Helicobacter Pylori ◽  
Migraine Without Aura ◽  
Oxidative Status ◽  
Helicobacter Pylori Infection ◽  
Igg Antibodies ◽  
No Bioavailability ◽  
Nitrite Nitrate ◽  
Plasma Nitrite

The study is aimed to ascertain whether the Helicobacter pylori ( Hp) infection is responsible for the vulnerability to oxidative stress observed in migraineurs. Hp sero-logical positivity was assessed by ELISA evaluation of specific IgA and IgG antibodies in 30 subjects (11 males and 19 females) suffering from migraine without aura during the headache-free period. The Hp infection was detected in 16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an index of systemic oxidative status, was increased in migraineurs without Hp infection with respect to controls ( P< 0.001), while no significant differences of TBA-RS were found in migraineurs with or without Hp infection. Unmodified values of plasma nitrite/nitrate concentrations, expression of systemic nitric oxide (NO), were obtained in migraineurs in comparison to controls indicating that Hp infection does not modify the plasma oxidative status and the systemic NO bioavailability of migraineurs. In conclusion, our results do not support any specific correlation between Hp infection and migraine.

Comparison of Effects of Nitric Oxide Synthase (NOS) Inhibitors on Plasma Nitrite/Nitrate Levels and Tissue NOS Activity in Septic Organs

2005 ◽  
Vol 49 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Yuri Hayashi ◽  
Masayoshi Abe ◽  
Akira Murai ◽  
Naomi Shimizu ◽  
Iku Okamoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nos Inhibitors ◽  
Nitrite Nitrate ◽  
Plasma Nitrite ◽  
Oxide Synthase
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