Nitric Oxide and Nitrogen Dioxide as Inducers of Acute Pulmonary Injury when Inhaled at Relatively High Concentrations for Brief Periods

Stavert, D. M.; Lehnert, Bruce E.

doi:10.3109/08958379009145245

Cited by 106 publications

(17 citation statements)

References 17 publications

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“…Using an adult rat model, Stavert and Lehnert (30) found that exposure of up to 1500 pprn of NO for 15 min or 1000 pprn NO for 30 min produced no detectable histopathologic change in the lungs, although rats exposed to 1000 pprn for 30 min became cyanotic and died due to methemoglobinemia. Exposure to 50 pprn NOz for 30 min produced an increase in lung weight, and histologic evidence of lung injury was observed after 30-min exposures to 25 pprn of NO2, but not at lesser exposure concentrations and times.…”

Section: Resultsmentioning

confidence: 99%

Nitric Oxide Reverses Acute Hypoxic Pulmonary Hypertension in the Newborn Piglet

et al. 1994

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ABSTRACT. Inhaled nitric oxide has been reported to act as a specific pulmonary vasodilator. We used the newborn piglet to create acute hypoxic pulmonary hypertension and examined the effect of inhaled nitric oxide in this model. Six newborn piglets were instrumented in order to measure cardiac index, pulmonary arterial pressure, and systemic arterial pressure. Pulmonary hypertension was induced by reducing the fraction of inspired oxygen to 0.12 to 0.14. With hypoxia (arterial oxygen saturation between 35 and 45%), pulmonary arterial pressure increased by 48% ( p < 0.01), pulmonary vascular resistance increased by 74% ( p < 0.01), and both systemic arterial pressure and systemic vascular resistance decreased by 38 and 31% respectively There is now good evidence that at a cellular level vascular muscle tone is regulated in large measure by NO or an NOrelated compound, which is thought to be identical to the previously described EDRF (1-4). Nitroso-containing vasodilators, such as nitroprusside, are thought to act through liberating NO in tissue (5, 6). NO is synthesized by the vascular endothelium from L-arginine (7, 8), and acts through the stimulation of guanylate cyclase, leading to the production of cyclic GMP (9. 10). The mechanism by which cyclic GMP relaxes vascular smooth muscle is not clear, but probably involves inhibition of activation-induced elevation in cytosolic calcium concentrationUsing a pulmonary hypertension model induced by the infusion of a thromboxane analog, heparin-protamine reaction, or hypoxia, Frostell, Fratacci and co-worker5 ( 12, 1 3) demonstrated reversal of pulmonary vasoconstriction using 40 to 80 ppm of inhaled NO without significant effect on the systemic circulation in 25-to 35-kg mature lambs. Similar results using pulmonary vasoconstriction produced by hypoxia with or without respiratory acidosis were obtained by Roberts et al. (14) who also demonstrated elevated plasma cyclic GMP levels after NO inhalation in a newborn lamb model. Kinsella et al. (1 5) evaluated the effects of NO in mechanically ventilated ovine fetuses maintained at intrauterine arterial oxygen levels. NO (5-20 ppm) produced an increase in pulmonary artery blood flow, an effect that was equal to the response seen when the Fioz was increased to 1 .O. In all of these studies there was no effect on the systemic circulation, specifically on SVR, and in two studies (14, 15) an increase in left-to-right shunting across the ductus occurred during NO inhalation, demonstrating that inhaled NO is a potent selective pulmonary vasodilator in these models.The aims of the current study were to investigate the feasibility of administering NO to a neonatal model, i.e. the 1-to 2-d-old piglet, and to evaluate the dose response characteristics and the time course of the effect of NO on hypoxic pulmonary vasoconstriction. MATERIALS AND METHODS

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Section: Resultsmentioning

confidence: 99%

Nitric Oxide Reverses Acute Hypoxic Pulmonary Hypertension in the Newborn Piglet

et al. 1994

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“…The test atmosphere enters from the top of the chamber and is delivered to the individual animal ports through a tube. A single-level, 12-port all glass exposure chamber was built for exposure of rats to oxidant gases (10). In this system, the gas flows past the rats' heads and exits through a tube at the bottom of the glass animal restraint tube.…”

Section: Nose-only Chambersmentioning

confidence: 99%

Exposing Animals to Oxidant Gases: Nose Only vs. Whole Body

Cheng¹,

Bowen²,

Rando³

et al. 2010

Proceedings of the American Thoracic Society

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Inhalation experiments using laboratory animals are performed under controlled conditions to assess the toxicity of and to investigate interventional strategies to ameliorate injury resulting from oxidant gas exposures. A variety of dynamic inhalation exposure systems that use whole-body or nose-only exposure chambers have been developed for rodents. In a whole-body exposure chamber, the animals are immersed in the test atmosphere, whereas in nose-only or head-only exposure systems, exposures are localized primarily to the head and/or nasal regions. There are advantages and disadvantages with both types of exposure approaches. Considerations such as animal number, exposure duration, end points of study, and availability of test material should influence the selection of a particular exposure system.

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“…The lungs (minus the RCL) were routinely filled at a pressure of 30 cm H20 with 10% formalin in phosphate-buffered saline for 48 hirs. For histological analysis of the lung, each left lobe was sliced on the same plane as the main-stem bronchi from its apex to its base along a line between the most posterior to the most anterior aspects to expose the maximal planar surface area for sectioning (1,4,8,13,15,16). The blocks of tissue were embedded in paraffin, and 4 •m sections were prepared and stained with hematoxylin and cosin by conventional methods.…”

Section: Animal Sacrifices Lung Gravimetric Measuremen•ts and Histomentioning

confidence: 99%

The Acute Inhalation Toxicity of Pyrolysis Products of Halon 1301: Kinetic Course of Lung Injury, Degradation in Work Performance, and Exercise Potentiation of Lung Injury after Phosgene Exposure

Lehnert¹

1992

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Nitric Oxide and Nitrogen Dioxide as Inducers of Acute Pulmonary Injury when Inhaled at Relatively High Concentrations for Brief Periods

Cited by 106 publications

References 17 publications

Nitric Oxide Reverses Acute Hypoxic Pulmonary Hypertension in the Newborn Piglet

Nitric Oxide Reverses Acute Hypoxic Pulmonary Hypertension in the Newborn Piglet

Exposing Animals to Oxidant Gases: Nose Only vs. Whole Body

The Acute Inhalation Toxicity of Pyrolysis Products of Halon 1301: Kinetic Course of Lung Injury, Degradation in Work Performance, and Exercise Potentiation of Lung Injury after Phosgene Exposure

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