Inhaled Nitric Oxide A Selective Pulmonary Vasodilator of Heparin-Protamine Vasoconstriction in Sheep

Fratacci, Marie-Dominique; Frostell, Claes; Chen, Tong-Yen; Wain, John C.; Robinson, Dwight R.; Zapol, Warren M.

doi:10.1097/00000542-199112000-00011

Cited by 269 publications

(81 citation statements)

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“…is required to mimic the effects of endogenous NO on pulmonary vasculature (Persson et al, 1994a), suggesting that this corresponds to endogenous concentrations. Also in favour of this concentration is that it has been used successfully in clinical trials (Frostell et al, 1993) and is considered relatively non-toxic (Fratacci et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

The promotion of patent airways and inhibition of antigen‐induced bronchial obstruction by endogenous nitric oxide

Persson

Friberg

Gustafsson

et al. 1995

British J Pharmacology

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1 The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2 Challenge with nebulised antigen (0.1-1 mg) elicited dose-dependent increases in insuflation pressure which were abolished by combined administration of histamine and leukotriene antagonists. 3 Challenge with nebulised antigen (0.1-mg) also elicited dose-dependent increases in the concentration of endogenous nitric oxide in the exhaled air. After an initial peak, exhaled NO concentrations returned to pre-challenge levels. 4 The increase in insufilation pressure and in exhaled NO caused by ovalbumin challenge was inhibited by combined administration of histamine and leukotriene antagonists. 5In non-immunised guinea-pigs, challenge of the airways with nebulised histamine (10-1000 nmol) or leukotriene C4 (LTC4, 30-300 pmol) elicited dose-dependent increases in insufflation pressure and in concentrations of endogenous NO in exhaled air. 6 The increase in exhaled NO correlated with the increase in insuiflation pressure in response to ovalbumin, histamine and LTC4. An inhibitor of endogenous NO synthesis, N-nitro-L-arginine methylester (L-NAME, 30 mg kg-' i.v.) abolished NO exhalation, and markedly augmented the airway responses to ovalbumin, histamine, or LTC4. 7 The potentiation by L-NAME of the increase in insufflation pressure in response to ovalbumin or histamine was prevented by exogenous NO (20 p.p.m.) in the inhaled air. 8 The results indicate that endogenous NO has an inhibitory effect on bronchial obstruction. Increased NO release during allergen challenge is likely to be due to actions of histamine and leukotrienes.

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Section: Discussionmentioning

confidence: 99%

The promotion of patent airways and inhibition of antigen‐induced bronchial obstruction by endogenous nitric oxide

Persson

Friberg

Gustafsson

et al. 1995

British J Pharmacology

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“…This is particularly serious since systemic hypotension impairs myocardial perfusion in a failing right ventricle (271. Hitherto, only inhaled nitric oxide has been shown to be a selective pulmonary vasodilator with a potential for clinical use [4, 5,9,28,29].…”

Section: Discussionmentioning

confidence: 99%

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia

Frostell¹,

Lönnqvist

Sonesson

et al. 1993

Anaesthesia

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SummaryThe addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises. Key wordsSurgery; congenital diaphragmatic hernia. Lung; blood flow. Complications; pulmonary hypertension. Gases, nonanaesthetic; nitric oxide.Pulmonary vasospasm with severe pulmonary hypertension is a much feared complication following surgery for congenital diaphragmatic hernia. The condition is difficult to manage and carries a substantial mortality [I]. State of the art therapy includes prophylactic hyperventilation, with careful control of acid-base balance and profound sedation. Life-threatening pulmonary hypertension with cardiac failure and refractory hypoxaemia may be treated with extracorporeal membrane oxygenation (ECMO), if available, although the use of this treatment is still controversial [2]. Pharmacological efforts to dilate the pulmonary vasculature often result in systemic dilatation and hypotension, since no vasodilator used so far has proved to be selective for the pulmonary vasculature.Nitric oxide has been identified as endothelium-derived relaxing factor (EDRF) [3]. Recently, the addition of low doses (5-80 parts per million, ppm) of nitric oxide to inspired gas has been shown to provide selective pulmonary vasodilatation in awake sheep [4, 51. Selective pulmonary vasodilatation with inhaled nitric oxide was also confirmed in healthy volunteers in whom acute pulmonary hypertension was provoked, by the inhalation of a hypoxic (12% 0,) gas mixture [6]. A similar effect was also found in patients with established pulmonary hypertension of varied aetiology [7-91. The rationale for inhalation of nitric oxide is to supply the vasodilator directly to the lung via the inspired gas, whilst its rapid inactivation by binding to haemoglobin in blood will protect the systemic vascular bed from its vasodilatator effects and the resultant unwanted systemic hypotension [4]. We report a case of near fatal pulmonary hypertension following surgical repair of congenital diaphragmatic hernia in a full term baby. Inhalation of nitric oxide, 5-10 ppm for 60 h, reversed hypoxaemia, reduced pulmonary hypertension and permitted a substantial reduction in ventilatory support. Case historyThe human ethics committee of the Karolinska Institute has approved the use of nitric oxide inhalation in patients

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“…Using awake lambs, Frostell and colleagues [49] used inhaled nitric oxide (5,10,20,40 and 80 ppm) to reverse pulmonary vasoconstriction induced by hypoxia and U-46619 (a thromboxane analogue). Fratacci and colleagues demonstrated that inhaled nitric oxide reversed the pulmonary hypertension induced by the protamine-heparin complex in awake lambs [50]. Methaemoglobin did not rise significantly in either study.…”

Section: Gaseous Nitric Oxidementioning

confidence: 95%

Nitric oxide: basic science and clinical applications

Kam

Govender

1994

Anaesthesia

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Inhaled Nitric Oxide A Selective Pulmonary Vasodilator of Heparin-Protamine Vasoconstriction in Sheep

Cited by 269 publications

References 0 publications

The promotion of patent airways and inhibition of antigen‐induced bronchial obstruction by endogenous nitric oxide

The promotion of patent airways and inhibition of antigen‐induced bronchial obstruction by endogenous nitric oxide

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia

Nitric oxide: basic science and clinical applications

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