Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Effects of hyperbaric oxygen and iloprost on intestinal ischemia-reperfusion induced acute lung injury

PURPOSE: To research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration. METHODS: Forty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination. RESULTS: Compared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group. CONCLUSION: Both HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.

Inhaled Iloprost as a First-Line Therapy for Persistent Pulmonary Hypertension of the Newborn

PURPOSE: Persistent pulmonary hypertension of the newborn (PPHN) is a potentially fatal disease. Inhaled iloprost, a stable analogue of prostacyclin, has recently been used as a therapeutic option. However, there are no clinical guidelines on the use of iloprost, specifically for neonates. This study aimed to suggest the use of inhaled iloprost as a rescue therapy for PPHN based on our experience.METHODS: The efficacy and adverse events of inhaled iloprost were evaluated prospectively in nine full-term neonates with PPHN. We monitored the following parameters: fraction of inspired oxygen (FiO₂), respiratory severity score (RSS), heart rate, and mean blood pressure.RESULTS: The inhalation dose was 1 to 2 µg/kg initially, and 4 to 8 inhalations per day were applied over 2 to 8 days, except in the case of one neonate who died 2 days after birth. Echocardiographic findings, changes in FiO₂, and RSS improved within the next 7 days in eight of the nine patients. Severe side effects on heart rate and blood pressure were not observed.CONCLUSION: Our experience suggests that inhaled iloprost can be used as a first-line treatment in newborn infants with PPHN when inhaled nitric oxide is not available. To the best of our knowledge, this report is the first prospective case series on the use of inhaled iloprost in PPHN.

Effect of aerosolized iloprost inhalation on pulmonary arterial pressure and hypoxic pulmonary vasocon-striction during one-lung ventilation / 临床麻醉学杂志

Objective To investigate the effect of aerosol inhalation of iloprost on pulmonary arterial pressure and hypoxic pulmonary vasoconstriction (HPV)during one-lung ventilation (OLV) in rats.Methods Thirty male rats were randomly divided into three groups,10 in each group. Models of lung perfusion were established,100% FiO 2 was ensured under the condition of OLV and the atomizers were opened.Atomization inhalation with normal saline was performed in group A,ilo-prost at a concentration of 0.05 μg·kg-1 ·min-1 in group B and iloprost at a concentration of 0.1μg·kg-1 ·min-1 in group C.Mean pulmonary artery pressure (MPAP)and PaO 2 of drainage-fluid from left atrium were recorded at time points of perfusion for 10 min (T1 ),aerosol inhalation for 10 min (T2 )and OLV for 1 h (T3 ).Oxygenation index (OI)was calculated with PaO 2 at each time point.Both lungs were harvested for electronic microscope detection.Results MPAPs at T2 and T3 were higher in contrast with that at T1 (P <0.05).A decrease of MPAP at T2 and T3 showed in group B and C when compared with those in group A (P <0.05).Group C had lower MPAP in comparison with group B at each time point.Considering the time span,we found that OIs at T2 and T3 were lower than that at T1 .In addition,OIs at T2 and T3 in group C were higher than those in group B,respectively.Under elec-tronic microscope,nuclear membranes typeⅡ alveolar epithelial cells of both lungs in group A and of non-ventilated lungs in group B and C bulged out or invaginated and lamellar bodies were evacuated,especially when compared to those in ventilated lungs in groups B and C.Conclusion In rat models of lung perfusion, atomization inhalation with iloprost can decreased MPAP,reduce intrapulmonary shunt and increase oxygen-ation.

Effects of iloprost on expression of Endothelin-1 in lung in rats with hypoxic pulmonary hypertension / 重庆医学

Objective To investigate the influence of iloprost on the expression of lung endothelin-1(ET-1) in rats with hypoxic pulmonary hypertension(HPH).Methods Thirty-two male SD rats were randomly divided into four groups:normal control (NC) group,normal treatment(NT) group,hypoxia control(HC) group,hypoxia treatment (HT) group.NC group and NT group raised under normal Oxygen conditions 3 weeks.HC and HT group placed in a low Oxygen chamber (O2 10％) were treated 3 weeks of hypoxia 8 hours per day.NT and HT group were treated daily iloprost by inhalation therapy (2μg/kg).Affer three weeks,measured mean pulmonary arterial pressure (mPAP),right ventricular systolic pressure (RVSP),index of right ventricular hypertrophy.HE staining was used to observe the morphological changes of pulmonary arteries and image analysis system was used to calculate the percentage of vascular wall thickness of small pulmonary arteries in each group,RT-PCR technique was used to assess the trends of ET-1 in lung tissue homogenates.Results The hemodynamics in HC group was significantly higher than other groups(P＜0.05),there was no significant statistically difference of the hemodynamics in HT group compare with normal control group.Pulmonary arteries morphology,vessel wall thickening and vessel lumina stenosis in HC group than NC、NT、group.These indicators were significant improved in HT group.ET-1 expression in lung tissue were significantly increased in HC group than NC groups.No significant difference was found between and NC group HT group.Conclusion Aerosol inhalation of iloprost has exact therapeutic effect for rats with HPH.Iloprost reduced ET-1 overexpression in lung tissue in HPH rats and prevent pulmonary vascular remodeling.

Pulmonary Arterial Hypertension is Normalized Following Six Years of Inhaled Iloprost Treatment in a Patient with Systemic Sclerosis

Pulmonary arterial hypertension is a critical manifestation of systemic sclerosis (SSc) and is a main cause of death. Several treatment modalities for SSc have been identified, with effects that improve quality of life and mortality rates. However, whether these drugs can also normalize pulmonary arterial pressure, remains unclear. Here, we report the case of a woman with diffuse SSc with pulmonary arterial hypertension, who had a functional status equivalent to the New York Heart Association class III. The patient was treated with inhaled iloprost. After six years of inhaled iloprost therapy, echocardiography showed that pulmonary arterial pressure normalized, accompanied by improvement in functional capacity. Inhaled iloprost might not only normalize pulmonary arterial pressure, but also improve the functional status of patients with SSc with pulmonary arterial hypertension.

Prueba de vasorreactividad con iloprost en hipertensión arterial pulmonar / Proof of vasoreactivity with iloprost in pulmonary arterial hypertension

Resumen Introducción: la detección de vasorreactividad pulmonar en hipertensión pulmonar es importante para determinar el beneficio del tratamiento con calcioantagonistas a largo plazo. En los últimos años se ha utilizado el iloprost como alternativa para la realización de la prueba con buenos resultados, por lo que es importante evaluar su respuesta en pacientes con esta enfermedad. Métodos: estudio cuasiexperimental no controlado con diseño de antes y después para evaluar la respuesta a un vasodilatador inhalado en pacientes remitidos al laboratorio de hemodinamia para pruebas de reactividad pulmonar. Se analizó una muestra no probabilística por conveniencia con la cohorte descrita. Se les realizó cateterismo derecho con medición de parámetros hemodinámicos y se evaluó la respuesta a la administración de 10 mcg de iloprost inhalado. Se consideró positiva la prueba si la presión arterial pulmonar media disminuía > 10 mmHg hasta < 40 mmHg, con aumento del gasto cardiaco o sin cambios en éste. Resultados: se incluyeron 30 pacientes; el promedio de edad fue de 55.5 ± 12 años, el 76.7% fueron mujeres y la fracción de eyección del ventrículo izquierdo fue de 52 ± 10%. La prueba se consideró positiva en 16.7% de los casos, sin complicaciones relacionadas al uso del medicamento. Se observó aumento no significativo del gasto cardiaco, con descenso importante en la resistencia vascular sistémica (1279 ± 438 vs 1110± 379, p=0.000004), resistencia vascular pulmonar (483 ± 210 vs 383 ± 185, p=0.000002), presión arterial pulmonar (47 ± 6 vs 39 ± 7, p=0.000002) y presión en cuña de la arteria pulmonar (16 ± 5 vs 15 ± 4, p<0.00009). Conclusión: el uso de iloprost inhalado en dosis de 10 mcg, en pacientes con hipertensión pulmonar llevados a cateterismo cardiaco derecho es una alternativa para identificar vasorreactividad, con baja tasa de eventos adversos. (Acta Med Colomb 2016; 40: 229-234).

Abstract Introduction: the detection of pulmonary vasoreactivity in pulmonary hypertension is important to determine the benefit of treatment with long-term calcium antagonists. In recent years, iloprost has been used as an alternative to perform the test with good results, so it is important to evaluate its response in patients with this disease. Methods: a quasi-experimental, uncontrolled study with before and after design to evaluate the response to an inhaled vasodilator in patients referred to the hemodynamic laboratory for pulmonary reactivity tests. A non-probabilistic sample was analyzed for convenience with the described cohort. Right catheterization was performed with measurements of hemodynamic parameters and the response to administration of 10 mcg of inhaled iloprost was performed in these patients. The test was considered positive if mean pulmonary artery pressure decreased >10 mmHg to <40 mmHg, with or without cardiac output increase. Results: 30 patients were included; mean age was 55.5 ± 12 years, 76.7% were women and the left ventricular ejection fraction was 52 ± 10%. The test was considered positive in 16.7% of cases, without complications related to the use of the drug. There was significant increase in cardiac output with an important decrease in systemic vascular resistance (1279 ± 438 vs 1110 ± 379, p = 0.000004), pulmonary vascular resistance (483 ± 210 vs 383 ± 185, p = 0.000002), blood pressure (47 ± 6 vs 39 ± 7, p = 0.000002), and wedge pressure of the pulmonary artery (16 ± 5 vs. 15 ± 4, p <0.00009). Conclusion: The use of inhaled iloprost in doses of 10 mcg in patients with pulmonary hypertension taken to right cardiac catheterization is an alternative to identify vasoreactivity with low rate of adverse events. (Acta Med Colomb 2016; 40: 229-234).

Comparison of inhaled nitric oxide and Iloprost in infants with moderate or severe pulmonary hypertension af-ter cardiac surgery:a prospective randomized trial / 中华实用儿科临床杂志

Objective To compare the efficacy of inhaled Iloprost and nitric oxide( NO)in infants with moderate or severe pulmonary hypertension(PH)after congenital heart disease surgery. Methods This was a prospec-tive randomized study in Children's Hospital of Fudan University from January 2011 to January 2014,including 40 in-fants who suffered from moderate to severe PH after heart surgery. Their ages ranged from 1 to 24 months. Their weight ranged from 3. 2 to 11. 0 kg. They were randomly allocated to inhale NO( NO group,n = 20)or Iloprost( Iloprost group,n = 20). Iloprost group was given Iloprost with 50 ng/(kg·min)for 10 min and then combined with NO 20 × 10 - 6 for 10 min;NO group was first given 20 × 10 - 6 of NO for 10 min,then combined with Iloprost 50 ng/(kg·min) for 10 min. Heart rate,systolic blood pressure,pulmonary artery pressure(PAP)and central venous pressure were recor-ded continuously. At the same time,the concentration of nitrogen dioxide and methemoglobin after inhaling NO was de-tected. Results Inhaled Iloprost and NO caused significant reduction in PAP(t = 4. 670,P = 0. 009;t = 3. 762,P =0. 004)and pulmonary - to - systemic pressure ratio(Pp/ Ps)(t = 16. 974,P = 0. 000;t = 9. 682,P = 0. 000)but signifi-cant increase in oxygen index separately. The combination had no additional effect compared with single application. In term of the reduction of PAP,there was no significant difference between inhaled Iloprost and NO(F = 2. 742,P =0. 129). The levels of nitrogen dioxide and methemoglobin were not above the normal limits. Conclusions Moderate to severe PH after cardiac surgery was significantly reduced by inhaled NO and Iloprost. They had similar effects. However, the combination of both vasodilators failed to prove more potent than either substance alone. Compared with the potential toxicity of NO,the individual differences and the complex transmission,Iloprost may be more reasonable and feasible for the postoperative treatment of PH.

Cambios agudos en la función auricular derecha post uso de iloprost inhalatorio en pacientes con hipertensión arterial pulmonar: estudio con técnicas de deformación de imagen / Acute changes in right atrial funcion after Iloprost inhalation in patients with pulmonary hypertension: a study using image deformation techniques

Introducción: El efecto de prostanoides inhalatorios sobre la función auricular derecha (AD) en hipertensión arterial idiopática (HAP) no ha sido estudiado. Objetivo: Evaluar cambios agudos en la función AD y función diastólica del ventrículo derecho en pacientes con HAP post uso de Iloprost inhalatorio. Métodos: Se incluyeron pacientes con HAP sin uso previo de prostanoides. Se realizó un ecocardiograma transtorácico basal y 30 min posterior a la inhalación de iloprost. Se midió dimensión AD, relación E/e' y strain de la AD por speckle tracking, registrando la onda negativa de contracción auricular (SaAD) y la onda positiva de la fase de reservorio (SsAD). Se midió el tiempo de inicio de la fase de reservorio AD durante el sístole ventricular. Resultados: Se estudiaron 16 pacientes (15 mujeres), con edad promedio 44 ± 7,8 años. Post Iloprost disminuyó el volumen AD (basal: 140ml, post Iloprost: 109 ml; p 0,008) y las presiones de llenado (E/e’ basal: 13, post Iloprost: 9,8; p 0,028). No se registraron diferencias en el SaAD (basal: -8,4%, post Iloprost: -8,5%; p 0,834). El SsAD fue mayor post Iloprost (basal: 8,6%, post Iloprost: 11,7%; p 0,002) iniciándose antes durante el sístole ventricular (basal: 445ms, post Iloprost: 368ms; p 0,001). Conclusión: Con Iloprost inhalatorio en pacientes con HAP se observa una reducción aguda en el tamaño de la AD y en las presiones de llenado del VD. La deformación durante la fase de reservorio de la AD aumenta y se inicia significativamente antes. Esto sugiere que el Iloprost podría mejorar en forma aguda el trabajo mecánico de la AD en paciente con HAP.

Background: The effects of inhaled prostanoids on right atrial (RA) function in patients with Pulmonary Arterial Hypertension (PAH) have not been studied. We evaluated acute changes in RA function and right ventricular diastolic function after inhaled iloprost. Methods: We included PAH patients without prior prostanoid treatment. A surface echocardiogram was performed at baseline and 30 minutes after iloprost inhalation. Measurements included RA dimensions, right E/e’ ratio and RA strain by speckle tracking, registering a RA contraction wave (RASa) and RA reservoir wave (RASs). RA time to peak of deformation during the reservoir phase was also measured. Results: We included 16 patients (15 females, aged 44±7.8 years. Post iloprost there was a reduction in RA volume (baseline: 140ml, post iloprost: 109ml; p 0.008) and right ventricular filling pressure (baseline E/e’: 13, post iloprost: 9.8; p 0.028). There was no difference in the magnitude of the RASa wave (baseline: -8.4%, post iloprost: -8.5%; p 0.834). The RASs wave was larger post iloprost (baseline: 8.6%, post iloprost: 11.7%; p 0.002), and began earlier (baseline RA time to peak of deformation during reservoir phase: 445ms, post iloprost: 368ms; p 0.001). Conclusion: Inhaled iloprost acutely reduces RA size and right ventricular filling pressure in patients with HAP It also significantly increases the magnitude of RA systolic deformation as well as making it occur earlier in RA filling phase. This suggests that iloprost might improve RA mechanical performance.

Inhaled iloprost for the treatment of patient with Fontan circulation / 소아과

Decreased exercise capacity after Fontan surgery is relatively common and the failure of the Fontan state gradually increases with age. However, there is no further treatment for patients with Fontan circulation. Pulmonary vasodilation therapy is an effective method to solve this problem because pulmonary vascular resistance is a major factor of the Fontan problem. Inhaled iloprost is a chemically stable prostacyclin analogue and a potent pulmonary vasodilator. We experienced two cases of Fontan patients treated with inhaled iloprost for 12 weeks. The first patient was an 18-year-old female with pulmonary atresia with an intact ventricular septum, and the second patient was a 22-year-old male with a double outlet right ventricle. Fifteen years have passed since both patients received Fontan surgery. While the pulmonary pressure was not decreased significantly, improved exercise capacity and cardiac output were observed without any major side effects in both patients. The iloprost inhalation therapy was well tolerated and effective for the symptomatic treatment of Fontan patients.

Efficacy of Inhaled Iloprost in Cor Pulmonale and Severe Pulmonary Hypertension Associated with Tuberculous Destroyed Lung

Chronic obstructive pulmonary disease (COPD) is one of the causes of cor pulmonale. Cor pulmonale patients with pulmonary hypertension have a significant lower survival rate than patients without. However, there is no conclusive treatment options in cor pulmonale and pulmonary hypertension associated with COPD until now. We report a patient with cor pulmonale and pulmonary hypertension associated with severe form of COPD and tuberculous destroyed lung who achieved marked clinical, functional and echocardiographic hemodynamic improvements with inhaled iloprost for six months.

A Case of Patient with Eisenmenger Syndrome Admitted to Intensive Care Unit Due to Septic Shock Complicated with Newlydiagnosed Down Syndrome and Moyamoya Disease / 대한구급학회지

Eisenmenger syndrome is a severe form of pulmonary arterial hypertension related to congenital cardiac defects. Many patients die at a young age from such complications. The treatment of primary pulmonary hypertension is being applied to Eisenmenger syndrome such as endothelin receptor antagonists, phosphodiesterase-5 blockers, and prostacyclin. We experienced a case of 29-year female with ventricular septal defect-related Eisenmenger syndrome complicated with Down syndrome and Moyamoya disease, who was admitted to intensive care unit due to enteritis-associated septic shock. After the combination treatment with iloprost and sildenafil within the intensive care unit, the patient was able to wean mechanical ventilation without further applications of invasive rescue therapy such as extracorporeal membrane oxygenator. She was later discharged with bosentan. She maintained bosentan therapy for 34 months continuously without aggravations of symptom but eventually died with intracranial hemorrhage, a complication of Moyamoya disease. To our knowledge, this is the first case report of Eisenmenger syndrome accompanied by mosaic Down syndrome and Moyamoya disease.

Tratamiento específico de la hipertensión arterial pulmonar. Experiencia de la policlínica de hipertensión pulmonardel Hospital Maciel, período 2009-2011 / Specific treatment of pulmonary arterial hypertension. Experience of the pulmonary hypertension clinic at the polyclinic Hospital Maciel, period 2009-2011

Introducción:la hipertensión pulmonar (HP) es una condición hemodinámica definida por un aumento de la presiónarterial pulmonar media (PmAP) 25 mmHg en reposo estimada mediante el cateterismo cardíaco derecho (CCD). Secomunica la experiencia adquirida en el diagnóstico, seguimiento y tratamiento de la hipertensión arterial pulmonar(HAP) y de la HP tromboembólica crónica (HPTEC) de la policlínica de HP del Hospital Maciel. Métodos: se analiza una cohorte de 15 pacientes (2009-2011). Se estimaron la clase funcional (CF), la prueba de caminata de 6 minutos (P6M), la excursión sistólica del plano del anillo tricuspídeo (ESPAT) y la velocidad sistólica pico(Sm). La severidad hemodinámica fue estimada por CCD. Se definió respuesta vasorreactiva aguda (RVA) positiva porel descenso de la PmAP 10 mmHg, alcanzando un valor absoluto 40 mmHg sin cambios o aumento del índice cardíaco (IC). Los datos se expresaron como media ± DS. Se empleó el test de t student pareado para comparar el efecto deltratamiento específico y el test de Kruskal-Wallis para comparaciones entre los grupos, con una p<0,05.Resultados:la edad promedio fue de 43 ± 12 años, 12 (80%) mujeres. Diez (67%) del grupo 1 y 5 (33%) del grupo 4. El20% se presentó en CF I-II y 80% en CF III-IV. El tiempo de seguimiento fue de 19 ± 11 meses. La ESPAT y la Sm basales fueron de 17 ± 7 mm y 11 ± 2 cm/s, respectivamente. La PmAP fue de 54 ± 15 mmHg, la presión auricular derecha 11± 6 mmHg, IC 2,1 ± 0,7 l/min/m2, resistencia vascular pulmonar 1.087 ± 625 dinas.s.cm-5, capacitancia pulmonar 1,3 ±0,6 ml/mmHg. Un paciente presentó RVA positiva. Se empleó sildenafil (100%), bosentan (50%) e iloprost (43%); en71% el tratamiento fue combinado. No se registró hepatotoxicidad por bosentan durante el período de seguimiento. Unpaciente murió por rechazo a recibir tratamiento específico. Los 14 pacientes restantes presentaron una mejoría de laCF (3,0 ± 0,8 versus 2,1 ± 0,8, p<0,05), así como de la P6M ...

Iloprosta reduz o dano colônico na colite isquêmica em ratos / Iloprost reduces colonic injury in ischemic colitis in rats

PURPOSE: Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. METHODS: Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. RESULTS: Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72th hour. CONCLUSION: Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage.

OBJETIVO: Avaliar os efeitos da administração de iloprosta no período precoce da colite isquêmica e o mecanismo da evolução destes efeitos. MÉTODOS: Trinta e dois ratos Wistar fêmeas em torno de 220g foram distribuídos em quatro grupos de oito ratos. No grupo 1 administração de iloprosta e sacrificados após 24 horas; no grupo 2 foram sacrificados após 24 horas sem iloprosta; no grupo 3 foi administrado iloprosta e sacrificados após 72 horas; no grupo 4 foram sacrificados após 72 horas sem Iloprosta. As diferenças entre os grupos no referente a dano tecidual. vascularização ou apoptose foi apurada estatisticamente. RESULTADOS: Dano oxidativo e apoptose foram menos acentuados e a vascularização foi melhor nos ratos que receberam iloprosta e sacrificados após 24 horas em contraste com os ratos que não receberam iloprosta. Porém, não houve diferença estatisticamente significante entre os grupos de 72 horas. CONCLUSÃO: Iloprosta inibe infiltração leucocitária, diminui a ação inflamatória de citoquinas e estimula angiogênese resultando em menor dano tecidual.

The Therapeutic Effect of Inhaled Iloprost in Newborn Infants with Severe Persistent Pulmonary Hypertension Refractory to Inhaled Nitric Oxide / 대한주산의학회잡지

Inhaled iloprost, a stable carbacyline derivative of prostacyclin, has been used recently for the treatment of adults with pulmonary hypertension but only few reports are available about its use in neonatal critical care. We report therapeutic trial of inhaled iloprost in newborn infants with persistent pulmonary hypertension of the newborn (PPHN) who did not respond to inhaled nitric oxide (iNO). Inhaled iloprost (Ventavis(R), Bayer Shering Pharma, Germany) was effective in neonates with severe PPHN who showed inadequate response to iNO. We suggest that inhaled iloprost could be considered as an additional therapeutic option in PPHN refractory to iNO.

The effect of perioperative inhaled iloprost on congenital heart disease with severe pulmonary arterial hypertension / 소아과

A 47-year-old male patient in whom atrial septal defect (ASD) had been diagnosed 15 years previously was admitted for cardiac catheterization. He had definite cyanotic lips and nail beds and severe pulmonary arterial hypertension (PAH). He had received medical treatment only for the last few years after being diagnosed with Eisenmenger syndrome. After cardiac catheterization, he received iloprost inhalation therapy pre and postoperation and was discharged after successful surgical closure of the ASD.

Inhaled iloprost and nitric oxide for pediatric pulmonary hypertension after congenital heart operation / 中华胸心血管外科杂志

Objective To investigate the hemodynamic effects and mechanisms of aerosolized iloprost in children with pulmonary hypertension(PAH)after congenital heart surgery,in the setting of early ventilation and continuous nitric oxide(NO)inhalation were administered.To observe the outcomes of the patients after iloprnst therapy.Methods From April 2008 to April 2009,all postoperative children with PAH in ICU,Fuwai hospital had regularly been given ventilation and NO inhalation at a dose of 10 ppm for 2 hours since they were leaving the operation room,and then ultrasonic cardiography was used to evaluate the systolic pulmonary arterial pressure(sPAP=4×TIVmax+RAP).Thirty children were diagnosed as having postoperative PAH for sPAP/sBP≥0.5.They were divided into two groups(group T and group C)randomly,with ventilation and NO inhalation administered continuously,and were given inhaled iloprost at a dose of 100 ng·kg-1·min-1*10 min and inhaled 0.9% NaCl 4ml respectively,once every 4 hours for 48 hours.We used the 24-hour cardiac monitors and ultrasonic cardiography for hemodynamic monitoring in the patients of two groups at the six time points:baseline(t1),20 min later after the first inhalation(t2),120 min later after the first inhalation(t3),24 hours later after the treatment(t4),48 hours later after the treatment(t5) and 24 hours after ceasing the last inhalation(t6).We examine the blood cAMP and cGMP by ELISA assay before and after the first inhalation.We observed the blood coagulation,the liver and kidney function of these patients.The outcomes of these patients were also investigated.Results At t1,the sPAP and sPAP/sBP had no differences between the two groups.At t2,the sPAP(43.23±11.72)mmHg and sPAP/sBP(0.48±0.13)in group T were both lower than the sPAP(53.13±13.60)mmHg and sPAP/sBP(0.60±O.15)in group C(P<0.05).At t3,the sPAP/sBP of group T was also lower than that of group C(0.48±0.09 vs 0.59±0.14,P<0.05).At t4 and t5,the sPAP in group T were (39.84±12.87)and(34.99±12.98)mm Hg,with sPAP/sBP(0.42±0.15)and(0.36±0.14),were much lower than those in group C(P<0.01).From t1 to t2,the cAMP level increased sharply from(406.64±179.18)to(578.68±193.05)pg/dl in group T(P<0.01),and was also obviously higher than that in group C at t2(392.26±94.46)pg/dl(P<0.01).HR,BP and RAP showed no notable difference between two groups at every time point.So did the PIP.There were no differences in coagulation,liver and kidney function at t6.2 patients died from pulmonary hypertension crisis(PAH)in group C and no one in group T.One patient showed flush during the treatment in group T and recovered spontaneously after the inhalation.Nevertheless,none in group C.Conclusiou Inhaled iloprost significantly improved pulmonary hemodynamics in children with PAH after congenital heart operation even thongh they were ventilated and inhaling NO.Increased blood cAMP level was considered to be a contributing factor.Howeve,systemic BP remain unaffected after iloprost inhalation.Aerosolized iloprost may be associated with improvement in the survival and deczeased PHC.

Safety management of 15 patients with severe pulmonary arterial hypertension treated by aerosolized iloprost / 中华护理杂志

This paper summarizes the key points of safety management for 15 patients with severe pulmonary arterial hypertension treated by aerosolized iloprost. All patients achieved significant improvements and none of them suffered any severe side effect. Complete safety management during the therapeutic procedure improved the patients' treatment confidence and compliance,and thereafter strengthened the efficacy of treatment.

Iloprost, a prostacyclin (PGI2) analogue, reduces liver injury in hepatic ischemiareperfusion in rats / Iloprost, um análogo da prostaciclina (PGI2), reduz danos da isquemia/reperfusão hepática em ratos

PURPOSE: To evaluate the effects of iloprost a prostacyclin analogue on the hepatic IR injury in rats. METHODS: Forty male Sprague-Dawley rats (250-300 g) were divided into four groups each containing 10 rats;(1)- controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats that underwent liver ischemia for 45 min followed by reperfusion for 45 min; (4) IR/ Iloprost group: rats pretreated with iloprost (10 µg kg-1, i.v). Liver tissues were taken to determine SOD, CAT, GSH, and MDA levels and for biochemical and histological evaluation. RESULTS: The plasma ALT and AST levels were increased in group 3 than in group 4. MDA values and the liver injury score decreased, while the SOD, CAT, and GSH values increased in group 4 compared to group 3. In group 3, hepatocytes were swollen with marked vacuolization. In group 4, there were regular sinusoidal structures with normal morphology without any signs of congestion. CONCLUSION: We demonstrated hepatoprotective effects of iloprost against severe ischemia and reperfusion injury in rat liver.

OBJETIVO: Avaliar os efeitos do iloprost, um análogo da prostaciclina nos danos causados ao fígado de ratos pela lesão de IR. MÉTODOS: Quarenta ratos machos Sprague-Dawley (250-300 g) foram distribuídos em quatro grupos de dez; - (1) grupo de controle: dados de animais não manipulados; (2) grupo "sham": ratos que sofreram intervenção cirúrgica sem I/R, aos quais foram administrados solução salina; (3) grupo I/R; animais que foram submetidos à isquemia por 45 minutos seguida de reperfusão por 45 minutos; (4) grupo I R/Iloprost: ratos previamente tratados com Iloprost ( 10µ kg-1, i.v). Tecidos hepáticos foram retirados para determinar os níveis de SOD, CAT, GSH, e MDA e para avaliação bioquímica e histológica. RESULTADOS: Os níveis de plasma ALT e AST aumentaram no grupo 3 mais do que no grupo 4. Os valores de MDA e o índice de lesões hepáticas diminuíram, enquanto os valores de SOD, CAT e GSH aumentaram no grupo 4, em comparação com o grupo3. No grupo 3, os hepatócitos se apresentaram edemaciados, e vacuolizados. No grupo 4, havia estruturas sinusoidais regulares, apresentando morfologia normal, sem sinais de congestão. CONCLUSÃO: Demonstramos os efeitos hepato-protetores do Iloprost contra a isquemia grave e o dano de reperfusão no fígado de ratos.

Use of Inhaled Iloprost in an Infant With Bronchopulmonary Dysplasia and Pulmonary Artery Hypertension

Pulmonary artery hypertension is a common cardiovascular complication in preterm infants with bronchopulmonary dysplasia which is associated with increased morbidity and mortality. Inhaled iloprost is used as a therapeutic option in pulmonary hypertension, especially in adults. There have been but a few reports on the use of iloprost for neonates and infants. We report the case of a 5 month-old-male infant who received neonatal intensive care for 4 months due to respiratory distress syndrome and prematurity, during which he developed bronchopulmonary dysplasia. Echocardiography showed severe pulmonary hypertension. The initial treatment included respiratory support with high frequency oscillatory ventilation (HFOV); however, his clinical condition did not improve. Inhaled iloprost with sildenafil, an oral phosphodiesterase-5 inhibitor, was thus used. With the administration of iloprost and sildenafil, his condition improved and he was weaned from oxygen. Our clinical experience suggests that iloprost is a promising therapy for pulmonary hypertension, especially when inhaled nitric oxide is unavailable.