A Prospective Trial of Inhaled Nitric Oxide in Clinical Lung Transplantation

Ardehali, A.; Laks, Hillel; Levine, Michael S.; Shpiner, Robert; Ross, David J.; Watson, Larry; Shvartz, Oleg; Sangwan, Susheela; Waters, Paul F.

doi:10.1097/00007890-200107150-00022

Cited by 95 publications

(43 citation statements)

References 18 publications

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“…Careful use of sedation and paralysis, close hemodynamic monitoring, and avoidance of nosocomial pneumonia are important. Nitric oxide has been shown to improve oxygenation, reduce pulmonary artery pressure without affecting systemic pressure, and shorten the duration of mechanical ventilation in case series (Date et al 1996;Ardehali et al 2001). Its primary effect is likely due to improvement in V/Q matching because NO is delivered to alveoli that are ventilated, although NO also has important anti-inflammatory properties related to neutrophil, macrophage, and platelet function (Coggins and Bloch 2007).…”

Section: Postoperative Carementioning

confidence: 99%

Overview of Clinical Lung Transplantation

Yeung

Keshavjee

2014

Cold Spring Harbor Perspectives in Medicine

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Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short-and long-term outcomes in the near future.

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Section: Postoperative Carementioning

confidence: 99%

Overview of Clinical Lung Transplantation

Yeung

Keshavjee

2014

Cold Spring Harbor Perspectives in Medicine

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“…NO possesses anti-inflammatory properties, and inhaled NO has been shown to attenuate pulmonary I-R injury in preclinical studies [51]. While two uncontrolled clinical studies suggested that inhaled NO may be beneficial in patients who develop lung I-R injury [52,53], a small randomized, placebo-controlled study demonstrated that inhaling NO (20 ppm) commencing 10 min after reperfusion did not affect the physiological or clinical outcome of patients after lung transplantation [54]. Additional studies will be required to define the therapeutic role of inhaled NO in patients who have developed I-R injury after lung transplantation.…”

Section: Treatment Of Pulmonary Ischemia-reperfusion Injurymentioning

confidence: 99%

Inhaled NO as a therapeutic agent

Bloch

Ichinose

Roberts

et al. 2007

Cardiovascular Research

139

101

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In 1991, Frostell and colleagues reported that breathing low concentrations of nitric oxide (NO) decreased pulmonary artery pressure (PAP) in awake lambs with experimental pulmonary hypertension (PH) [Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 1991;83:2038-47]. Subsequently, efforts of multiple research groups studying animals and patients led to approval of inhaled NO by the US Food and Drug Administration in 1999 and the European Medicine Evaluation Agency and European Commission in 2001. Inhaled NO is currently indicated for the treatment of term and near-term neonates with hypoxemia and PH. Since regulatory approval, several studies have suggested that NO inhalation can prevent chronic lung disease in premature infants. In addition, unanticipated systemic effects of inhaled NO may lead to treatments for a variety of disorders including ischemia-reperfusion injury. This review summarizes the pharmacology and physiological effects of breathing NO. The application of inhaled NO to hypoxemic neonates with PH is discussed including recent studies exploring the use of inhaled NO to prevent bronchopulmonary dysplasia in premature infants. This review also highlights the application of inhaled NO to treat adults with cardiopulmonary disease, strategies to augment the efficacy of inhaled NO, and potential applications of the systemic effects of the gas.

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“…Inhaled NO has been shown to attenuate ischemia-reperfusion injury in the lung and other organs in preclinical 55 and in clinical studies. 56,57 However, a recent randomized, placebo-controlled study demonstrated that inhaling 20 ppm NO beginning 10 minutes after reperfusion does not affect the physiological or clinical outcome of patients after lung transplantation. 58 …”

Section: Inhaled No To Treat Ischemia-reperfusion Injurymentioning

confidence: 99%

Inhaled Nitric Oxide

2004

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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...

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A Prospective Trial of Inhaled Nitric Oxide in Clinical Lung Transplantation

Abstract: Prophylactic-inhaled NO does not prevent RI in human lung transplantation. However, inhaled NO, started at reperfusion, improves gas exchange and reduces pulmonary artery pressure in those patients who develop RI.

Cited by 95 publications

References 18 publications

Overview of Clinical Lung Transplantation

Overview of Clinical Lung Transplantation

Inhaled NO as a therapeutic agent

Inhaled Nitric Oxide

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