Modulators of Nitric Oxide in Porcine Endotoxemia: Effects on Hepatic Oxygen Delivery and Consumption

1997 ◽  
Vol 29 (4) ◽  
pp. 237-245 ◽  
Author(s):  
Y. Gundersen ◽  
T. Sætre ◽  
H. Carlsen ◽  
T. Scholz ◽  
P. Lilleaasen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Delivery ◽  
Hepatic Oxygen Delivery

Hepatic oxygen metabolism in porcine endotoxemia: the effect of nitric oxide synthase inhibition

1998 ◽  
Vol 275 (6) ◽  
pp. G1377-G1385 ◽  
Author(s):  
Torunn Saetre ◽  
Yngvar Gundersen ◽  
Otto A. Smiseth ◽  
Tim Scholz ◽  
Hege Carlsen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Delivery ◽  
Statistical Significance ◽  
Liver Blood Flow ◽  
Oxygen Metabolism ◽  
Extraction Ratio ◽  
Oxygen Extraction ◽  
Oxygen Extraction Ratio ◽  
Circulatory Effects ◽  
Hepatic Oxygen Delivery

The role of endotoxin (lipopolysaccharide, LPS) and nitric oxide in hepatic oxygen metabolism was investigated in 36 pigs receiving 1) LPS (1.7 μg ⋅ kg−1 ⋅ h−1) for 7 h and N G-nitro-l-arginine methyl ester (l-NAME; 25 mg/kg) after 3 h, 2) LPS, 3) NaCl andl-NAME, and 4) NaCl. Infusion of LPS reduced hepatic oxygen delivery (Do 2H) from 60 ± 4 to 30 ± 5 ml/min ( P < 0.05) and increased the oxygen extraction ratio from 0.29 ± 0.07 to 0.68 ± 0.04 after 3 h ( P < 0.05). Hepatic oxygen consumption (V˙o 2H) was maintained (18 ± 4 and 21 ± 4 ml/min, change not significant), but acidosis developed. Administration ofl-NAME during endotoxemia caused further reduction of Do 2H from 30 ± 3 to 13 ± 2 ml/min ( P < 0.05) and increased hepatic oxygen extraction ratio from 0.46 ± 0.04 to 0.80 ± 0.03 ( P< 0.05). There was a decrease inV˙o 2H from 13 ± 2 to 9 ± 2 ml/min that did not reach statistical significance, probably representing a type II error. Acidosis was aggravated. Administration of l-NAME in the absence of endotoxin also increased the hepatic oxygen extraction ratio, but no acidosis developed. In a different experiment, liver blood flow was mechanically reduced in the presence and absence of endotoxin, comparable to the flow reductions caused byl-NAME. The increase in hepatic oxygen extraction ratio (0.34) and maximum hepatic oxygen extraction ratio (∼0.90) was similar whether Do 2H was reduced by occlusion or byl-NAME. We concluded thatl-NAME has detrimental circulatory effects in this model. However, neither endotoxin norl-NAME seemed to prevent the ability of the still circulated parts of the liver to increase hepatic oxygen extraction ratio to almost maximum when oxygen delivery was reduced. The effect of l-NAME on oxygen transport thus seems to be caused by a reduction in Do 2H rather than by alterations in oxygen extraction capabilities.

scholarly journals Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia–reperfusion model involving aortic clamping

2018 ◽  
Vol 31 ◽  
pp. 039463201775148 ◽  
Author(s):  
Waldemar Gozdzik ◽  
Stanisław Zielinski ◽  
Marzena Zielinska ◽  
Kornel Ratajczak ◽  
Piotr Skrzypczak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Mrna Expression ◽  
Oxygen Delivery ◽  
Ischemia Reperfusion ◽  
Systemic Inflammatory Response ◽  
Inhaled Nitric Oxide ◽  
Tlr4 Expression ◽  
Sham Surgery ◽  
Tlr4 Mrna

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia–reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)—sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

17β-Estradiol decreases hypoxic induction of erythropoietin gene expression

2002 ◽  
Vol 283 (2) ◽  
pp. R496-R504 ◽  
Author(s):  
Harshini Mukundan ◽  
Thomas C. Resta ◽  
Nancy L. Kanagy
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Oxygen Delivery ◽  
Chronic Hypoxia ◽  
No Synthase ◽  
No Production ◽  
Enos Expression ◽  
Hypoxic Induction ◽  
Endothelial No Synthase ◽  
17Β Estradiol

Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17β-estradiol (E2-β) inhibits this effect. We hypothesized that E2-β decreases EPO gene expression during hypoxia. Because E2-β can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-β inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-β (20 μg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O2) or normoxia. We found that E2-β treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-β treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-β decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.

Hepatic oxygen delivery-consumption relationship during anesthesia and hypoxemia in dogs

1995 ◽  
Vol 9 (2) ◽  
Author(s):  
Nobuyuki Matsumoto ◽  
Yutaka Mizumoto ◽  
K�ichir� Hori ◽  
Yasuo Murakami ◽  
Sinichi Nakamura ◽  
...  
Keyword(s):  
Oxygen Delivery ◽  
Hepatic Oxygen Delivery

Role of nitric oxide in the coupling of myocardial oxygen consumption and coronary vascular dynamics during pregnancy in the dog

2007 ◽  
Vol 293 (4) ◽  
pp. H2479-H2486 ◽  
Author(s):  
Jeffrey G. Williams ◽  
Tibisay Rincon-Skinner ◽  
Dong Sun ◽  
Zipping Wang ◽  
Suhua Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Oxygen Delivery ◽  
Myocardial Oxygen Consumption ◽  
Left Ventricular ◽  
Tissue Samples ◽  
Enalapril Maleate ◽  
Protein Levels ◽  
Nitrite Production

We examined the ability of cardiac endothelial nitric oxide synthase (eNOS) to couple myocardial oxygen consumption (MV̇o2) and oxygen delivery during pregnancy. Awake dogs were studied using echocardiography before and at 40 days, 50 days, and 60 days (60D) of pregnancy and at ∼14 days postpartum. Left ventricular eNOS, phosphorylated eNOS, and copper, zinc-superoxide dismutase (CuZnSOD or SOD-1) were determined by immunoblotting. MV̇o2 of left ventricular tissue samples was measured in vitro in response to increasing doses of bradykinin, enalapril maleate, and amlodipine. We examined the changes in passive diameter and flow-dependant arteriolar dilation of coronary arterioles. Echocardiography indicated increases in cardiac output (∼60%) during pregnancy. Myocardial eNOS (21 ± 4%), phosphorylated eNOS (19 ± 3%), and SOD-1 (61 ± 2.7%) protein levels were significantly increased at 60D. Bradykinin, enalapril maleate, and amlodipine (10−4 mol/l) decreased MV̇o2 in a nitric oxide-dependant manner (by 24 ± 1.3% in controls and 34 ± 2.2% at 60D; by 21 ± 1.1% in controls and 29 ± 1.1 at 60D; and by 22 ± 2.5% in controls and 26 ± 1.0% at 60D, respectively). Arterioles from pregnant dogs showed increased flow-dependant dilation in response to increased shear stress and larger passive diameter. Nitrite production was stimulated by bradykinin and carbachol in microvessels in vitro; pregnancy enhanced nitrite release. Myocardial eNOS, phosphorylated eNOS, and SOD-1 protein expression are increased during pregnancy, and this increase is associated with enhanced nitric oxide-dependant control of MV̇o2. Thus increases in eNOS and SOD-1 promote the coupling of oxygen delivery and efficiency in the heart during pregnancy.

scholarly journals Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology

2020 ◽  
Vol 126 (1) ◽  
pp. 129-158 ◽  
Author(s):  
Richard T. Premont ◽  
James D. Reynolds ◽  
Rongli Zhang ◽  
Jonathan S. Stamler
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Delivery ◽  
Tissue Oxygenation ◽  
Common Factor ◽  
Well Being ◽  
Therapeutic Interventions ◽  
Oxygen Binding ◽  
Metabolic Demand ◽  
Hypoxic Vasodilation

A continuous supply of oxygen is essential for the survival of multicellular organisms. The understanding of how this supply is regulated in the microvasculature has evolved from viewing erythrocytes (red blood cells [RBCs]) as passive carriers of oxygen to recognizing the complex interplay between Hb (hemoglobin) and oxygen, carbon dioxide, and nitric oxide—the three-gas respiratory cycle—that insures adequate oxygen and nutrient delivery to meet local metabolic demand. In this context, it is blood flow and not blood oxygen content that is the main driver of tissue oxygenation by RBCs. Herein, we review the lines of experimentation that led to this understanding of RBC function; from the foundational understanding of allosteric regulation of oxygen binding in Hb in the stereochemical model of Perutz, to blood flow autoregulation (hypoxic vasodilation governing oxygen delivery) observed by Guyton, to current understanding that centers on S-nitrosylation of Hb (ie, S-nitrosohemoglobin; SNO-Hb) as a purveyor of oxygen-dependent vasodilatory activity. Notably, hypoxic vasodilation is recapitulated by native S-nitrosothiol (SNO)–replete RBCs and by SNO-Hb itself, whereby SNO is released from Hb and RBCs during deoxygenation, in proportion to the degree of Hb deoxygenation, to regulate vessels directly. In addition, we discuss how dysregulation of this system through genetic mutation in Hb or through disease is a common factor in oxygenation pathologies resulting from microcirculatory impairment, including sickle cell disease, ischemic heart disease, and heart failure. We then conclude by identifying potential therapeutic interventions to correct deficits in RBC-mediated vasodilation to improve oxygen delivery—steps toward effective microvasculature-targeted therapies. To the extent that diseases of the heart, lungs, and blood are associated with impaired tissue oxygenation, the development of new therapies based on the three-gas respiratory system have the potential to improve the well-being of millions of patients.

Methaemoglobinaemia in the perioperative period with regional block

2021 ◽  
Vol 14 (9) ◽  
pp. e245135
Author(s):  
Arianna Cook ◽  
Stuart Grant ◽  
Sharon Kapeluk ◽  
Patrick Steele
Keyword(s):  
Nitric Oxide ◽  
Differential Diagnosis ◽  
Case Report ◽  
Oxygen Delivery ◽  
Perioperative Period ◽  
Interesting Case ◽  
Erector Spinae ◽  
Dissociation Curve ◽  
Oxyhaemoglobin Dissociation Curve ◽  
Anaesthetic Gases

Methaemoglobin is a form of haemoglobin with oxidised ferric (+3) iron rather than ferrous (+2) iron, which causes a leftward shift in the oxyhaemoglobin dissociation curve and prevents oxygen delivery. Anaesthesiologists need to be familiar with this differential diagnosis for hypoxia given the use of drugs in the perioperative setting known to induce methaemoglobinaemia, including benzocaine and lidocaine, antibiotics such as dapsone and anaesthetic gases, including nitric oxide. This case report details an interesting case of symptomatic methaemoglobinaemia in the perioperative period in the setting of dapsone use and an erector spinae block performed with ropivacaine.

Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs

1990 ◽  
Vol 258 (6) ◽  
pp. G910-G918 ◽  
Author(s):  
K. Nagano ◽  
S. Gelman ◽  
E. L. Bradley ◽  
D. Parks
Keyword(s):  
Reperfusion Injury ◽  
Oxygen Delivery ◽  
Oxygen Supply ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Venous Blood ◽  
Oxygen Demand ◽  
Base Line ◽  
Hepatic Oxygen Delivery ◽  
Normothermic Group

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.

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