RESUMEN
BACKGROUND: Raised concentrations of nitrate and nitrite have been found in exhaled breath condensate (EBC) in airway disease, and it has been postulated that this reflects increased nitric oxide (NO) metabolism. However, the chemical and anatomical origin of nitrate and nitrite in the airways has not yet been sufficiently studied. METHODS: The fraction of exhaled NO at an exhalation flow rate of 50 ml/s (FE(NO)) and nitrite and nitrate in EBC, nasal condensate, and saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects, all of whom were non-smokers without respiratory disease. Tracheal and oral samples were taken from the tracheostomised subjects and nasal (during velum closure) and oral samples from the non-tracheostomised subjects. Measurements were performed before and after sodium nitrate ingestion (10 mg/kg) and use of antibacterial mouthwash (chlorhexidine 0.2%). RESULTS: In tracheostomised subjects oral FE(NO) increased by 90% (p<0.01) while tracheal FE(NO) was not affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were increased 23-fold at 60 minutes (p<0.001) whereas the nitrite levels in tracheal EBC showed only a minor increase (fourfold, p<0.05). Nitrate was increased the same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p<0.05). In non-tracheostomised subjects oral FE(NO) and EBC nitrite increased after nitrate ingestion and after chlorhexidine mouthwash they approached baseline levels again (p<0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in oral EBC or saliva, whereas significant reductions were seen after antibacterial mouthwash (p<0.05 and p<0.001, respectively). CONCLUSIONS: Besides the salivary glands, plasma nitrate is taken up by the lower airways but not the nasal airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is reduced to nitrite by bacterial activity which takes place primarily in the oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to contribute to exhaled NO in non-inflamed airways, and there is also a substantial contribution of nitrite from the oropharyngeal tract during standard collection of EBC.
Asunto(s)
Nitratos/análisis , Óxido Nítrico/metabolismo , Nitritos/análisis , Adulto , Anciano , Antiinfecciosos Locales/farmacología , Pruebas Respiratorias , Clorhexidina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antisépticos Bucales/farmacología , Nitratos/administración & dosificación , Nitratos/metabolismo , Nitritos/metabolismo , Nariz/química , Saliva/química , TraqueostomíaRESUMEN
BACKGROUND: Pulmonary endothelial dysfunction may occur after ischaemia-reperfusion injury and can be revealed as a reduced vasodilatory response upon administration of acetylcholine (ACh). ACh also releases the endothelium-derived vasodilator nitric oxide but direct measurements of this gas are difficult to perform in vivo. We wanted to study the effects of i.v. administration of ACh and the endothelium-independent vasodilator nitroglycerin on exhaled nitric oxide in relation to pulmonary endothelial dysfunction after open-heart surgery and cardiopulmonary bypass (CPB). METHODS: Basal exhaled nitric oxide and the response in exhaled nitric oxide to i.v. injections of ACh and nitroglycerin were measured with chemiluminescence in 10 patients before and after open-heart surgery. RESULTS: Exhaled nitric oxide decreased significantly after CPB. I.V. bolus injections of ACh induced a reproducible and dose-dependent increase in exhaled nitric oxide that was unaltered after CPB. In contrast, the increase in exhaled nitric oxide evoked by nitroglycerin was attenuated after CPB. The response in pulmonary vascular resistance index (PVRI) to an infusion of ACh decreased after CPB, indicating endothelial dysfunction. The decrease in PVRI response to ACh correlated to the duration of CPB. CONCLUSIONS: Interestingly, pulmonary vascular dysfunction after CPB was accompanied by a reduction in the exhaled nitric oxide response to nitroglycerin and lower levels of basal exhaled nitric oxide. The ACh-induced responses in exhaled nitric oxide were unchanged, which could indicate nitric oxide-independent mechanisms behind the endothelial dysfunction in this study. The possibility of using exhaled nitric oxide dynamics to investigate pulmonary endothelial dysfunction merits further studies.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Óxido Nítrico/metabolismo , Complicaciones Posoperatorias/metabolismo , Daño por Reperfusión/metabolismo , Acetilcolina/farmacología , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Pruebas Respiratorias/métodos , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/farmacología , Complicaciones Posoperatorias/fisiopatología , Arteria Pulmonar/fisiopatología , Daño por Reperfusión/fisiopatología , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
The ex utero intrapartum treatment (EXIT) procedure is a method of maintaining utero-placental circulation during cesarean section to gain time to secure a potentially obstructed fetal airway. Four cases of the EXIT procedure are described with special reference to the maternal anesthetic technique. Deep volatile anesthesia (approximately 2 MAC) with isoflurane or sevoflurane for a prolonged period of time, in three cases in combination with an intravenous nitroglycerin infusion, was used to ensure a fully relaxed uterus during the procedure. All mothers were maintained hemodynamically stable with preserved utero-placentary perfusion. It was possible to intubate the tracheas of two fetuses, whereas in the other two tracheostomies had to be performed. Fetal gas exchange was not negatively affected during the EXIT procedure as evidenced by normal blood gas values in the umbilical artery at the time of delivery. After reducing the concentration of volatile anesthetic, delivery of the neonate and administration of oxytocin, uterine contractility was promptly re-established and there were no signs of uterine atony in the postoperative period. All four neonates survived the procedure without complications.
Asunto(s)
Obstrucción de las Vías Aéreas/congénito , Obstrucción de las Vías Aéreas/terapia , Anestesia por Inhalación , Anestesia Obstétrica , Cesárea/métodos , Adulto , Anestésicos por Inhalación , Quistes/congénito , Quistes/terapia , Femenino , Hipoxia Fetal/prevención & control , Hipoxia Fetal/terapia , Neoplasias de Cabeza y Cuello/congénito , Neoplasias de Cabeza y Cuello/terapia , Humanos , Recién Nacido , Intubación Intratraqueal , Isoflurano , Laringoestenosis/congénito , Laringoestenosis/terapia , Masculino , Éteres Metílicos , Enfermedades de la Boca/congénito , Enfermedades de la Boca/terapia , Nitroglicerina/uso terapéutico , Embarazo , Sevoflurano , Tocolíticos/uso terapéutico , TraqueostomíaRESUMEN
Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation. Ten tracheotomized patients and seven healthy subjects were studied. The mean+/-SEM fraction of exhaled NO from the nose, mouth and trachea was 56+/-8, 14+/-4 and 6+/-1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64+/-14, 11+/-3 and 4+/-1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation. There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.