Methods: An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high-pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid- and slow-response chemiluminescence analyzers. The ventilator was set for constant-flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s.
Results: The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow-response chemiluminescence analyzer was used. 相似文献
Methods: Inhaled nitric oxide (80 ppm) was administered before tourniquet application and continued throughout reperfusion until the completion of surgery. Venous blood samples were collected before and after reperfusion, for the measurements of nitrate and nitrite, CD11b/CD18, soluble P-selectin, and lipid hydroperoxide. Muscle biopsies were obtained from the quadriceps muscle before skin closure and analyzed for myeloperoxide, conjugated dienes, and nuclear factor-[kappa]B translocation.
Results: Administration of inhaled nitric oxide (80 ppm) significantly attenuated the inflammatory response characterized by reduced expression of CD11b/CD18, P-selectin, and nuclear factor [kappa]B compared with the control group. This was accompanied by increased plasma levels of nitrate and nitrite and reduced oxidative stress. 相似文献
Methods: Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli 0111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured.
Results: Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75 +/- 0.25, 1.25 +/- 0.25, 1.75 +/- 0.25 mmHg) than in lungs of control rats (3 +/- 0.5, 4.25 +/- 0.25, 4.5 +/- 0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75 +/- 0.25, 4.5 +/- 0.25, 4.5 +/- 0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0 +/- 1.0, 4.0 +/- 1.0, 4.0 +/- 0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75 +/- 0.25, 2.25 +/- 0.5, 2.75 +/- 0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness. 相似文献
Methods: After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14), NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (t0), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively.
Results: Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (+13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure. 相似文献
Methods. A left lung, which had been preserved for 24 hours, was transplanted and a right pneumonectomy was performed in 5 pigs. After a 24-hour observation period the pigs inhaled 5, 20, and 80 ppm nitric oxide, and pulmonary vascular resistance was recorded continuously. From the same donors preserved pulmonary arteries from the contralateral lung were studied simultaneously in organ baths. Acetylcholine chloride was used to elicit endothelium-dependent relaxation in vessel segments contracted with the thromboxane A2 analogue U-46619.
Results. Maximal endothelium-dependent relaxation decreased in the preserved lungs and correlated to the pulmonary vascular resistance in the simultaneously transplanted lungs. Inhalation of nitric oxide in the pigs that had received transplants caused the pulmonary vessels to dilate in proportion to the endothelial dysfunction.
Conclusions. Preservation of lung for transplantation induces an endothelial dysfunction, and the degree of the decrease in pulmonary vascular resistance caused by nitric oxide inhalation may be an indication of the degree of this endothelial damage. The vasodilation caused by inhaled nitric oxide increases as the endothelial function deteriorates. 相似文献
Introduction and Objectives
Inhaled nitric oxide (iNO) is a gaseous drug with known properties of specific pulmonary vasodilation and improved oxygenation. In some clinical trials on lung transplantation (LT) in animals, it has been demonstrated to reduce primary graft dysfunction (PGD) by limiting neutrophil adhesion and the inflammatory cascade. Our objective was to assess whether iNO showed this immunomodulatory effect by determining interleukin (IL)-6, -8, and -10 levels in blood and bronchoalveolar lavage (BAL) in LT patients, and its relationship with PGD incidence.Materials and Methods
Forty-nine LT patients were recruited and included in the iNO or in the control group. Patients in the first group were given iNO (10 ppm) from the start of LT to 48 hours afterward. BAL and blood samples were taken preimplantation and at 12, 24, and 48 hours after graft reperfusion.Results
The iNO group displayed a significantly lower incidence (P < .035) of PGD (17.2%) than the control group (45%). Significant differences (P < .05) were also observed in the iNO group with lower levels of IL-6 (in blood at 12 hours), IL-8 (in blood and BAL at 12 and 24 hours), and IL-10 (in blood at 12 and 24 hours and BAL at 24 hours).Conclusions
PGD is associated with the development of an inflammatory process that is reduced by giving iNO to lung recipients. In our series, the iNO group displayed significantly lower content of IL-6, IL-8, and IL-10 in the majority of samples at 12 and 24 hours compared with the control group. 相似文献Methods: Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 micro Meter) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 micro Meter), and Kfc was estimated at baseline and after 30 min of reperfusion.
Results: (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. 相似文献
Methods: The vasorelaxation to inhaled NO was studied in isolated, perfused, and ventilated lungs obtained from mice 16 h after an intraperitoneal challenge with saline or 50 mg/kg Escherichia coli lipopolysaccharide. In some mice, challenge with saline or lipopolysaccharide was followed by intraperitoneal administration of N-acetylcysteine, dimethylthiourea, EUK-8, or polyethylene glycol-conjugated catalase.
Results: The pulmonary vasodilator response of U46619-preconstricted isolated lungs to ventilation with 0.4, 4, and 40 ppm inhaled NO in lipopolysaccharide-challenged mice was reduced to 32, 43, and 60%, respectively, of that observed in saline-challenged mice (P < 0.0001). Responsiveness to inhaled NO was partially preserved in lipopolysaccharide-challenged mice treated with a single dose of N-acetylcysteine (150 or 500 mg/kg) or 20 U/g polyethylene glycol-conjugated catalase (all P < 0.05 vs. lipopolysaccharide alone). Responsiveness to inhaled NO was fully preserved by treatment with either dimethylthiourea, EUK-8, two doses of N-acetylcysteine (150 mg/kg administered 3.5 h apart), or 100 U/g polyethylene glycol-conjugated catalase (all P < 0.01 vs. lipopolysaccharide alone). 相似文献