RESPIR MED 2007 OCT101(10)212532 EPUB 2007 JUL 20 LINKS

1 NEONATAL RESPIRATORY DISTRESS INCLUDING CPAP CLINICAL LEARNING RESOURCE
17 TABLE 1 COMMON MICROBIOTA OF THE RESPIRATORY TRACT
20 PREVENTION OF RESPIRATORY INSUFFICIENCY AFTER SURGICAL MANAGEMENT (PRISM)

21 NCAC 46 2610 MEDICAL GAS OXYGEN AND RESPIRATORY
22 PROPAGACIÓN DE INFECCIONES HIGIENE RESPIRATORIA
22 PROPAGACIÓN DE INFECCIONES HIGIENE RESPIRATORIA

Respir Med

Respir Med. 2007 Oct;101(10):2125-32. Epub 2007 Jul 20. Links

Hypoxia-induced pulmonary hypertension: different impact of iloprost, sildenafil, and nitric oxide.

Weissmann N, Gerigk B, Kocer O, Nollen M, Hackemack S, Ghofrani HA, Schermuly RT, Butrous G, Schulz A, Roth M, Seeger W, Grimminger F.

University of Giessen Lung Center (UGLC), Medical Clinic II/V, Justus-Liebig University Giessen, Klinikstrasse 36, 35392 Giessen, Germany. [email protected]

OBJECTIVES: Chronic alveolar hypoxia induces pulmonary hypertension, evident from elevated pulmonary artery pressure (PAP), pulmonary vascular resistance, right ventricular hypertrophy (RVH), and increased muscularization of the pulmonary vasculature. Additionally, the vasoconstrictor response to acute hypoxia (HPV) may be reduced in the remodeled vasculature. However, no direct comparison of different treatments on the various parameters characterizing pulmonary hypertension has been performed yet. Against this background, we compared the effects of inhaled NO, infused iloprost, a stable prostacyclin analogue, and oral sildenafil, a phosphodiesterase 5 inhibitor, on hypoxia-induced pulmonary hypertension. METHODS: Exposure of rabbits to chronic hypoxia (FiO(2)=0.10) for 42 days. Treatment with infused iloprost, oral sildenafil, and inhaled nitric oxide. RESULTS: We quantified PAP, pulmonary vascular resistance, RVH, vascular remodeling, vasoreactivity, and the strength of HPV. Chronic hypoxia resulted in an increase in (a) the right ventricle/(left ventricle+septum) ratio from 0.26+/-0.01 to 0.44+/-0.01, (b) PAP, and (c) the degree of muscularization from 14.0+/-4.0% to 43.5+/-5.3%. Treatment with iloprost and sildenafil, but not with NO, prevented the increase in muscularization. In contrast, RVH was strongly inhibited by sildenafil, whereas NO had some minor, and iloprost had no effect. Only iloprost reduced PAP compared to NO and sildenafil. The downregulation of HPV was abrogated only by NO. CONCLUSION: We demonstrated (a) that the parameters characterizing hypoxia-induced pulmonary hypertension are not functionally linked, (b) that the downregulation of HPV under chronic hypoxia can be prevented by inhaled NO but not by sildenafil and iloprost, and (c) that iloprost is particularly effective in preventing vascular remodeling and sildenafil in preventing RVH.

PMID: 17643279 [PubMed - indexed for MEDLINE]

: Chest. 2004 Feb;125(2):580-6. Links

Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension.

Leuchte HH, Schwaiblmair M, Baumgartner RA, Neurohr CF, Kolbe T, Behr J.

Department of Internal Medicine I, Section for Pulmonary Diseases, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany. [email protected]

STUDY OBJECTIVES: Different vasodilators and different routes of application are used for the treatment of primary pulmonary hypertension (PPH). Recently, sildenafil, a phosphodiesterase-V inhibitor, has been shown to have beneficial hemodynamic effects in PPH. However, the hemodynamic effects of sildenafil have not been characterized and compared to other vasodilators such as inhaled nitric oxide (iNO) or iloprost in PPH in the same group of patients. STUDY DESIGN: We investigated prospectively 10 consecutive patients with PPH using iNO, iloprost aerosol, and oral sildenafil to test acute hemodynamic response during right-heart catheterization. RESULTS: iNO, iloprost aerosol, and sildenafil caused a significant fall of mean pulmonary artery pressure and pulmonary vascular resistance (PVR) [p < 0.05]. Correspondingly, cardiac output and mixed venous saturation increased slightly in all groups. Systemic arterial pressure and vascular resistance were mainly unaltered. Using a PVR reduction of > or =20% to define a significant response, 7 of 10 patients were responders to iloprost aerosol, whereas 4 of 10 patients responded to iNO and oral sildenafil. Improvement of oxygenation as indicated by an increase of arterial oxygen tension was observed with iloprost aerosol (p < 0.01). CONCLUSION: All of the three substances, iNO, iloprost aerosol, and oral sildenafil, significantly improved pulmonary hemodynamics in patients with PPH. The most prominent hemodynamic effects and improvement of oxygenation were observed with iloprost aerosol.

1: Circulation. 2002 May 21;105(20):2398-403. Links

Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide.

Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S.

Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Canada. [email protected]

BACKGROUND: The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO. METHODS AND RESULTS: We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001). CONCLUSIONS: A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.

49714 §497—SCHEDULE OF RATINGS–RESPIRATORY SYSTEM 49714 §497 SCHEDULE OF
54 FISIOLOGÍA RESPIRATORIO RESPIRATORIO 1 MECÁNICA RESPIRATORIA VOLUMEN
AIRSTREAM MECHANISMS PULMONIC MOVEMENT OF LUNG AIR BY RESPIRATORY

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