Nitric oxide inhalation and nitric oxide synthase inhibitor supplement for endotoxin‐induced hypotension

Suzuki, Satoshi; Togari, Hajime; Yamaguchi, Nobuyuki; Haas, Kelly Mullins

doi:10.1046/j.1442-200x.2001.01419.x

Cited by 5 publications

(4 citation statements)

References 34 publications

(89 reference statements)

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“…It is worth noting that increased pressure in pulmonary circulation during sepsis is associated with a reduced patient survival [ 13 ]. Numerous studies besides our own have shown that administration of inhaled NO may normalize increased pulmonary arterial pressure [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

R-100 improves pulmonary function and systemic fluid balance in sheep with combined smoke-inhalation injury and Pseudomonas aeruginosa sepsis

et al. 2017

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BackgroundSeptic shock is a major cause of death in intensive care units around the world . The aim of the study was to investigate whether the novel drug R-100 (a superoxide degradation catalyst and nitric oxide donor) improves pulmonary function in a sheep model of septic shock caused by Pseudomonas aeruginosa and smoke inhalation.MethodsEleven female sheep were prepared surgically and randomly assigned to a treatment group (n = 5) or a control group (n = 6) after inhalation of cooled cotton smoke and airway instillation of live P. aeruginosa (2.5 × 1011 CFU) by bronchoscope under deep anesthesia and analgesia. The treatment group received an intravenous infusion of a total of 80 mg/kg of R-100 diluted in 500 mL of 5% dextrose. The control group was given 500 mL of 5% dextrose. All animals received intravenous lactated Ringer’s solution to maintain a hematocrit level at baseline ± 3%. Blood gas and hemodynamics were measured at baseline and then analyzed every 3 h during the 24-h study period. Results are expressed as mean ± SEM.ResultsThe treated animals showed significant improvement in their pulmonary gas exchange (PaO2/FiO2 ratio at 24 h: 246 ± 29 vs. 90 ± 40 mmHg control, P < 0.05). Pulmonary arterial pressures were reduced in the treated group (24 h: 26 ± 1 vs. 30 ± 2 cm mmHg control, P < 0.05). The treated animals also had an improved total fluid balance after 24 h (190 ± 45/24 h mL vs. 595 ± 234/24 h mL control, P < 0.05).ConclusionsTreatment with R-100 improves pulmonary gas exchange and blood oxygenation, and prevents a fluid imbalance in sheep subjected to smoke inhalation and P. aeruginosa.

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Section: Introductionmentioning

confidence: 99%

R-100 improves pulmonary function and systemic fluid balance in sheep with combined smoke-inhalation injury and Pseudomonas aeruginosa sepsis

et al. 2017

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“…The findings show partially beneficial effects and suggest that this approach deserves further evaluation (11, 12). However, it is not known whether NOS blockade, in hemodynamically stable lung injury, is associated with improved oxygenation with NO inhalation.…”

Section: Introductionmentioning

confidence: 87%

“…Prior studies on the effects of combined treatment, with blockade of NOS and NO inhalation, have been reported on both neonatal and adult models of experimental sepsis and endotoxemia (10-12), where recovery of the systemic blood pressure by blockade of NOS and simultaneous attenuation of pulmonary hypertension by NO inhalation were targeted. The findings show partially beneficial effects and suggest that this approach deserves further evaluation (11, 12).…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with N-nitro-L-arginine Methyl Ester Improved Oxygenation After Inhalation of Nitric Oxide in Newborn Piglets with Escherichia coli Pneumonia and Sepsis

Chang

Kang

et al. 2006

J Korean Med Sci

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We evaluated the effects of a combined therapy of pre-blockade endogenous nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn piglets were randomized into 5 groups: control, E. coli pneumonia control, pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI. Only two of 8 animals with L-NAME-pretreated pneumonia survived. Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection. This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.

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“…L-NAME) or an iNOS inhibitor (aminoguanidine) is deleterious, but the use of N w-nitro-L-arginine (L-NNA) prevents hypotension. [106][107][108] These investigations are inconclusive as to the role of NO in sepsis-induced hypotension. Use of an angiotensin receptor 2 antagonist alone or with a bradykinin B2 receptor antagonist may be beneficial in sepsis.…”

Section: Summary and Implications For Therapymentioning

confidence: 99%

Review: The plasma kallikrein/kinin and renin angiotensin systems in blood pressure regulation in sepsis

Shariat‐Madar

2004

Journal of Endotoxin Research

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The hemodynamics of septic shock after endotoxinemia is influenced by the plasma kallikrein/kinin and the renin angiotensin systems. In recent years, new information has improved understanding of the protein/biologically active peptide interactions between these two systems. The plasma kallikrein/kinin system, more commonly known as the contact system, has undergone a re-evaluation as to how it assembles on cell membranes for physiological and pathophysiological activation and as to its role in Gram-negative sepsis. It has been proposed that it counterbalances the plasma renin angiotensin system. Furthermore, more knowledge about the renin angiotensin system has become available on how it either opposes the actions of the kallikrein/kinin system or, in some cases, summates with it. Understanding the interactions between these two systems may lead to development of better pharmacological treatments for endotoxin-induced shock.

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Nitric oxide inhalation and nitric oxide synthase inhibitor supplement for endotoxin‐induced hypotension

Cited by 5 publications

References 34 publications

R-100 improves pulmonary function and systemic fluid balance in sheep with combined smoke-inhalation injury and Pseudomonas aeruginosa sepsis

R-100 improves pulmonary function and systemic fluid balance in sheep with combined smoke-inhalation injury and Pseudomonas aeruginosa sepsis

Pretreatment with N-nitro-L-arginine Methyl Ester Improved Oxygenation After Inhalation of Nitric Oxide in Newborn Piglets with Escherichia coli Pneumonia and Sepsis

Review: The plasma kallikrein/kinin and renin angiotensin systems in blood pressure regulation in sepsis

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