Delivery of Inhaled Nitric Oxide Using the Ohmeda INOvent Delivery System

Kirmse, Max; Hess, Dean; Fujino, Yuji; Kacmarek, Robert M.; Hurford, William E.

doi:10.1378/chest.113.6.1650

Cited by 40 publications

(24 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One hour after delivery, iNO was administered to the experimental group at a level of 5 ppm with an INOVent according to established procedures (26). The NO gas and INOVent were kindly provided by iNO Therapeutics (Clinton, NJ).…”

Section: Methodsmentioning

confidence: 99%

Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

McCurnin

Pierce

Chang

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

195

153

View full text Add to dashboard Cite

Nitric oxide (NO) serves multiple functions in the developing lung, and pulmonary NO production is decreased in a baboon model of chronic lung disease (CLD) after premature birth at 125 days (d) gestation (term = 185d). To determine whether postnatal NO administration alters the genesis of CLD, the effects of inhaled NO (iNO, 5 ppm) were assessed in the baboon model over 14d. iNO caused a decrease in pulmonary artery pressure in the first 2d and a greater rate of spontaneous closure of the ductus arteriosus, and lung compliance was greater and expiratory resistance was improved during the first week. With iNO, postmortem pressure-volume curves were shifted upward, lung DNA content and cell proliferation were increased, and lung growth was preserved to equal that which occurs during the same period in utero. In addition, the excessive elastin deposition characteristic of CLD was normalized by iNO, and there was evidence of stimulation of secondary crest development. Thus, in the baboon model of CLD, iNO improves early pulmonary function and alters lung growth and extracellular matrix deposition. As such, NO biosynthetic pathway dysfunction may contribute to the pathogenesis of CLD.

show abstract

Section: Methodsmentioning

confidence: 99%

Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

McCurnin

Pierce

Chang

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

195

153

View full text Add to dashboard Cite

show abstract

“…71 In a simulation using a model lung and commercially available ventilators, production of NO 2 during NO inhalation at 20 ppm appears to be minimal (Ͻ0.7 ppm) even with an FiO 2 of 95%. 72 Inhaled NO can combine with Hb to form nitrosylhemoglobin, which is rapidly oxidized to metHb. The rates of uptake and release of NO from ferrous (Fe 2ϩ ) Hb are 10 5 -to 10 6 -fold greater than those of oxygen.…”

Section: Toxicity and Side Effects Of Inhaled Nomentioning

confidence: 99%

Inhaled Nitric Oxide

2004

View full text Add to dashboard Cite

Since the recognition of nitric oxide (NO) as a key endothelial-derived vasodilator molecule in 1987, the field of NO research has expanded to encompass many areas of biomedical research. It is now well established that NO is an important signaling molecule throughout the body. The therapeutic potential of inhaled NO as a selective pulmonary vasodilator was suggested in a lamb model of pulmonary hypertension and in patients with pulmonary hypertension in 1991. 1,2 Because NO is scavenged by hemoglobin (Hb) on diffusing into the blood and is thereby rapidly inactivated, the vasodilatory effect of inhaled NO is limited largely to the lung. This is in contrast to intravenously infused vasodilators that can cause systemic vasodilation and severe systemic arterial hypotension.Recent data indicate that inhaled NO can be applied in various diseases. For example, studies suggest that inhaled NO is a safe and effective agent to determine the vasodilatory capacity of the pulmonary vascular bed. This article summarizes the pharmacology and physiology of inhaled NO and reviews the current uses of inhaled NO for the treatment, evaluation, and prevention of cardiovascular and respiratory diseases. Pharmacology and Physiology of Inhaled NO Chemistry of NO GasNO is a colorless, odorless gas that is only slightly soluble in water. 3 NO and its oxidative byproducts (eg, NO 2 and N 2 O 4 ) are produced by the partial oxidation of atmospheric nitrogen in internal combustion engines, in the burning cinder cones of cigarettes, and in lightning storms. Medical-grade NO gas is produced under carefully controlled conditions, diluted with pure nitrogen, and stored in the absence of oxygen. The recent article by Williams 4 provides a review of the chemistry of NO. Therapeutic Versus Endogenous NO Concentrations in the AirwayAlthough early studies of inhaled NO in the treatment of pulmonary hypertension used concentrations of 5 to 80 ppm, it has since been realized that concentrations Ͼ20 ppm provide little additional hemodynamic benefit in most patients. In some adults with acute respiratory failure, the effective concentrations of inhaled NO required to improve oxygenation can be as low as 10 ppb. 5,6 Of note, NO has been detected in exhaled human breath. The majority of exhaled NO in normal humans appears to be derived from nasal bacterial flora (25 to 64 ppb), with lower concentrations measured in the mouth, trachea, and distal airway (1 to 6 ppb). 5,7 Mechanism of ActionAfter inhalation, NO diffuses rapidly across the alveolarcapillary membrane into the subjacent smooth muscle of pulmonary vessels to activate soluble guanylate cyclase (Figure 1). This enzyme mediates many of the biological effects of NO and is responsible for the conversion of GTP to cGMP. Increased intracellular concentrations of cGMP relax smooth muscle via several mechanisms. The physiological actions of cGMP are limited to its area of synthesis by its hydrolysis to GMP by cyclic nucleotide phosphodiesterases (PDE) or by its export from the cell. Of the 11 reported...

show abstract

“…These hemodynamic measurements were performed in a blinded manner. To explore a possible pulmonary vascular reactivity, RVSP measurements were performed in CCR7 Ϫ/Ϫ and WT mice, which were tracheotomized and connected to a rodent ventilator (model 874092, B. Braun, Melsungen, Germany) at baseline (room air) and after inhalation of 40 ppm nitric oxide (NO) (37) for 5 min using the INOvent delivery system (Datex-Ohmeda, Madison, WI) (28). The injector module of NO was adapted into the circuit, and gas samples were taken immediately before the ventilator to control that inhaled NO was 40 Ϯ 1 ppm.…”

Section: Methodsmentioning

confidence: 99%

Lack of CCR7 induces pulmonary hypertension involving perivascular leukocyte infiltration and inflammation

Larsen

Yndestad²,

Sjaastad

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The chemokine receptor CCR7 regulates lymphocyte trafficking, and CCR7 deficiency induces infiltration of T and B cells adjacent to vessels in mouse lungs. Perivascular infiltration of T and B cells has also been found in human pulmonary arterial hypertension, and downregulation of the CCR7 receptor in circulating leukocytes of such patients has been observed. To investigate whether changes in the CCR7 system contribute to the pathogenesis of pulmonary hypertension, we utilized mice deficient of the CCR7 receptor. The cardiopulmonary and inflammatory responses of CCR7 depletion were evaluated in CCR7-deficient and wild-type mice. Measurements of cytokines upregulated in the animal model were also performed in patients with pulmonary hypertension and controls and in vascular smooth muscle cells. We found that mice lacking CCR7 had increased right ventricular systolic pressure, reduced pulmonary artery acceleration time, increased right ventricular/tibial length ratio, Rho kinase-mediated pulmonary vasoconstriction, and increased muscularization of distal arteries, indicating pulmonary hypertension. These mice also showed increased perivascular infiltration of leukocytes, consisting mainly of T and B cells, and increased mRNA levels of the inflammatory cytokines interleukin-12 and CX3CL1 within pulmonary tissue. Increased serum levels of interleukin-12 and CX3CL1 were also observed in patients with pulmonary hypertension, particularly in those with pulmonary hypertension associated with connective tissue disorder. In smooth muscle cells, interleukin-12 induced secretion of the angiogenic cytokine interleukin-8. We conclude that these results suggest a role for CCR7 in the development of pulmonary arterial hypertension, at least in some subgroups, possibly via pulmonary infiltration of lymphocytes and secretion of interleukin-12 and CX3CL1.

show abstract

Delivery of Inhaled Nitric Oxide Using the Ohmeda INOvent Delivery System

Cited by 40 publications

References 16 publications

Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease

Inhaled Nitric Oxide

Lack of CCR7 induces pulmonary hypertension involving perivascular leukocyte infiltration and inflammation

Contact Info

Product

Resources

About