Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets

Schreiber, Michael D.; Dixit, Rajeev; Rudinsky, Brian; Hipps, Robert; Morgan, Sherwin; Keith, A; Meadow, William

doi:10.1097/00003246-200211000-00026

Cited by 14 publications

(4 citation statements)

References 26 publications

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“…Inhaled alternatives to NO, including sodium nitroprusside (31,32), nebulized nitroglycerine (32,33), and various NONOates (34) have shown promise but are less well understood from the standpoint of structure-function relationships. We recently showed that the nitrosalcohol gas ENO has activity similar to that of NO but is resistant to reactions with O 2 that generate potentially toxic NO x .…”

Section: Discussionmentioning

confidence: 99%

A Novel Inhaled Organic Nitrate That Affects Pulmonary Vascular Tone in a Piglet Model of Hypoxia-Induced Pulmonary Hypertension

et al. 2005

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Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extracorporeal membrane oxygenation, but it has potential toxicities, especially in an oxygen-rich environment. A number of other NO-based molecules have been given by inhalation, but their structure-function relationships have not been established. Recent studies have raised the idea that toxic and beneficial properties can be separated. We synthesized a novel organic nitrate [ethyl nitrate (ENO 2 )], tested it in vitro, and administered it to hypoxic piglets. ENO 2 lowered pulmonary artery pressure and raised the PO 2 in arterial blood but did not alter systemic vascular resistance or methemoglobin levels. In addition, we tested the effect of ENO 2 in the presence of the thiol glutathione, both in vivo and in vitro, and found its action to be enhanced. Although ENO 2 is less potent than inhaled NO on a doseequivalency basis, pretreatment of hypoxic animals with glutathione, which may be depleted in injured lungs, led to a markedly enhanced effect (largely mitigating the difference in potency). The disease entity persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance (PVR) after birth leading to extrapulmonary right-to-left shunting through the patent foramen ovale and patent ductus arteriosus with resulting systemic arterial hypoxemia. These patients are frequently treated with inhaled nitric oxide (NO) and may require extracorporeal membrane oxygenation; those with severe respiratory failure are at increased risk for neurodevelopmental impairment (1,2). NO's clinical effectiveness has been well documented (3-6), although some reports suggest that it may exacerbate lung inflammation (7), raising the concern that it may have toxic properties in some clinical settings. Infants who receive inhaled NO for PPHN are often treated with high inspired oxygen, and in the O 2 -rich environment of the lung, higher oxides of nitrogen (NO x ) including peroxynitrite may form (8), which can cause hemorrhage, inflammation, and edema (9,10). Airways of animal and human subjects who have received inhaled NO showed the same patterns of oxidative injury found in animals and humans who were exposed to NO x or hyperoxia (11,12).Inhaled, exogenous NO is delivered to well-ventilated parts of the lung and will stimulate guanylate cyclase activity, leading to vascular smooth muscle relaxation. Thus, NO has been effective in lowering pulmonary artery pressure (PAP)

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Section: Discussionmentioning

confidence: 99%

A Novel Inhaled Organic Nitrate That Affects Pulmonary Vascular Tone in a Piglet Model of Hypoxia-Induced Pulmonary Hypertension

et al. 2005

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“…When administered through a nebulizer connected to the inspiratory limb of the breathing circuit, SNP has been shown to be a selective pulmonary vasodilator. [ 22 23 ] In a porcine model of PH,[ 24 ] nebulized SNP (total dose of 25 mg) caused a rapid reduction in PAP that was equivalent to iNO at 20 ppm, without decreasing MAP. In a sheep model of PH,[ 25 ] low-dose inhaled SNP (concentration ≤0.02 M) decreased PAP by 42% and systemic vascular resistance (SVR) by 5%.…”

Section: Inhaled Nitric Oxide Donorsmentioning

confidence: 99%

Inhaled therapy for the management of perioperative pulmonary hypertension

2015

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Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

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“…2 There are several differences between the two studies. Based on our preliminary animal studies, 3,4 we were able to use a much higher dose of sodium nitroprusside. Second, Palhares' study group was comprised of 50% premature infants (gestational age range, 28-36 weeks), whereas our study was limited to term infants.…”

Section: Replymentioning

confidence: 99%

Nebulized sodium nitroprusside

Palhares

2004

The Journal of Pediatrics

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Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets

Cited by 14 publications

References 26 publications

A Novel Inhaled Organic Nitrate That Affects Pulmonary Vascular Tone in a Piglet Model of Hypoxia-Induced Pulmonary Hypertension

A Novel Inhaled Organic Nitrate That Affects Pulmonary Vascular Tone in a Piglet Model of Hypoxia-Induced Pulmonary Hypertension

Inhaled therapy for the management of perioperative pulmonary hypertension

Nebulized sodium nitroprusside

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