El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar / Melatonin modulates the expression of pulmonary prostanoids

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Anesthesia for pulmonary trunk aneurysmorrhaphy / Anestesia para aneurismorrafia de tronco de artéria pulmonar

Abstract Background and objectives: The aneurysm in the pulmonary trunk is a rare disease. Because of its location, a rupture can lead to right ventricular failure and sudden death. Aneurysmorraphy is the most widely used surgical treatment in these cases. The aim of this study is to report a successful balanced general anesthesia for aneurysmorraphy of pulmonary trunk. Case report: Male patient, 28 years, asymptomatic, diagnosed with an aneurysm in the pulmonary trunk. According to the location of the aneurysm and the consequent failure of the pulmonary valve, an aneurysmorraphy was indicated, with implantation of vascular-valvular prosthesis (valved tube). We opted for a balanced general anesthesia, seeking to prevent an increase in systemic and pulmonary vascular resistances, thus avoiding to cause stress on the wall of the aneurysmal vessel. Conclusions: A balanced general anesthesia, in combination with adequate ventilation to prevent elevation in pulmonary vascular pressure, was appropriate for surgical repair of an aneurysm in the pulmonary trunk.

Resumo Justificativa e objetivos: O aneurisma de tronco de artéria pulmonar é uma doença rara. Por sua localização, uma ruptura pode conduzir à falência do ventrículo direito e à morte súbita. A aneurismorrafia é o tratamento cirúrgico mais usado nesses casos. O objetivo foi relatar uma anestesia geral balanceada para aneurismorrafia de tronco de artéria pulmonar feita com sucesso. Relato do caso: Paciente do sexo masculino, 28 anos, assintomático, diagnosticado com aneurisma de tronco de artéria pulmonar. De acordo com a localização do aneurisma e a consequente insuficiência da válvula pulmonar, foi indicada a aneurismorrafia com implante de prótese vascular e valvular (tubo valvado). Optou-se pela anestesia geral balanceada, para impedir um aumento nas resistências vasculares sistêmicas e pulmonar e evitar-se, dessa maneira, um estresse sobre a parede do vaso aneurismático. Conclusões: A anestesia geral balanceada, em associação com uma ventilação adequada para evitar elevação na pressão vascular pulmonar, foi apropriada para correção cirúrgica de um aneurisma em tronco pulmonar.

Adherence to standard precautions from the standpoint of the Health Belief Model: the practice of recapping needles / Adesão às precauções padrão sob o prisma do Modelo de Crenças em Saúde: a prática de reencapar agulhas

The aim of this study was to applythe Health Belief Model to explain the adherence to the recommendation not to recap needles by dentists and dental assistants of the public health system in a municipality in the State of São Paulo. A questionnaire validated and adapted for the oral health area was used, which included variables related to the frequency of recapping and health beliefs using Likert-type scales. The relationship between beliefs and adherence to the recommendation not to recap needles was obtained by regression analysis. Of all the professionals in this study (n=79), the majority (83.5%) reported recapping needles at least once in the last month. Through regression analysis, it was observed that the relationship between the beliefs described by the model and the attitude whether or not to follow the recommendation not to recap needles was explained by a lower perception of psychological barriers and a greater perception of stimuli not to recap needles. The conclusion reached is that the acceptance of recommendations to prevent working accidents with biological material was explained by some dimensions of the Health Belief Model, enabling discussion about reformulation of training offered to professionals of the public health system.

Objetivou-se neste estudo aplicar o Modelo de Crenças em Saúde a fim de explicar a adesão à recomendação de não reencapar agulhas por cirurgiões-dentistas e auxiliares de saúde bucal da rede pública de um município paulista. Utilizou-se um questionário validado e adaptado para a área de saúde bucal, que contemplava variáveis relativas à frequência do reencape e crenças em saúde, por meio de escalas tipo Likert. A relação entre as crenças e a adesão à recomendação de não reencapar agulhas foi obtida por meio da análise de regressão. Da amostra de profissionais obtida por adesão ao estudo (n = 79), a maioria (83,5%) relatou ter reencapado agulhas pelo menos alguma vez no último mês. Por meio da análise de regressão, foi observado que a relação entre as crenças descritas pelo modelo e a atitude de aderir ou não à recomendação de não reencapar agulhas foi explicada por uma menor percepção de barreiras psicológicas e por uma maior percepção de estímulos para não reencapar agulhas. Conclui-se que a aceitação das recomendações para prevenir acidentes do trabalho com material biológico foi explicado por algumas dimensões do Modelo de Crenças em Saúde, possibilitando a discussão sobre a reformulação de capacitações oferecidas para profissionais do sistema público de saúde.

Meta-analysis of randomized controlled trials of bosentan for treatment of pulmonary arterial hypertension

BACKGROUND/AIMS: We assessed the efficacy and safety of bosentan in patients with pulmonary arterial hypertension (PAH). METHODS: We surveyed randomized controlled trials (RCTs) of the efficacy and safety of bosentan in patients with PAH using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. Results are presented as odds ratios (ORs) or weighted mean differences (WMDs). RESULTS: Meta-analysis of seven RCTs including a total of 410 patients and 296 controls revealed that the 6-minute work distance was significantly higher in the bosentan group than in the placebo group (WMD, 46.19; 95% confidence interval [CI], 21.20 to 71.19; p = 2.9 x 10(-5)). Compared with the placebo, bosentan significantly reduced the mean pulmonary arterial pressure in patients with PAH (WMD, -6.026; 95% CI, -8.785 to -3.268, p = 1.8 x 10(-6)). The bosentan therapy group worsened less clinically than the placebo group (OR, 0.252; 95% CI, 0.140 to 0.454; p = 4.6 x 10(-7)). The incidence of serious adverse events did not differ between the bosentan and placebo groups (OR, 0.948; 95% CI, 0.556 to 1.614; p = 0.843). However, the results of the abnormal liver function test (LFT) were significantly higher in the bosentan group than in the placebo group (OR, 2.312; 95% CI, 1.020 to 5.241; p = 0.045). CONCLUSIONS: This meta-analysis shows that bosentan can treat PAH effectively. However, bosentan increased the incidence of abnormal LFT results compared with the placebo.

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Effect of Small Hairpin RNA Targeting Endothelin-Converting Enzyme-1 in Monocrotaline-Induced Pulmonary Hypertensive Rats

The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ETA) were significantly decreased in the shRNA group in week 4. The protein levels of ETA were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-alpha and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.

Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study / Efecto de la dieta rica en colesterol, la infección recurrente, y las posibles modalidades de tratamiento sobre el sistema vascular pulmonar: un estudio experimental

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection - Group II (n = 9), infection-cholesterol rich diet - Group III (n = 12), infection-cholesterol rich dietcefepime - Group IV (n = 11); infection-cholesterol rich diet-diclofenac potassium - Group V (n = 9); infection-cholesterol rich diet and red wine - Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However, antibiotics and anti-inflammatory agents could be useful in prevention.

OBJETIVO: La infección puede conducir a inflamación, ateroesclerosis y eventos vasculares trombóticos. El efecto aterosclerótico de la hipercolesterolemia en el sistema vascular es bien conocido. Sin embargo, se hicieron estudios limitados sobre los agentes preventivos y terapéuticos. El objetivo de este estudio fue investigar los efectos de la infección y la dieta rica en colesterol, combinados con agentes antibióticos, anti-inflamatorios, y vino tinto, sobre el sistema vascular pulmonar. MÉTODOS: Cincuenta y nueve ratas fueron evaluadas. Se hicieron seis grupos: grupo-control I (n = 10), grupo-infección II (n = 9), grupo infección-dieta rica en colesterol III (n = 12), grupo-infección-dieta rica en colesterol-cefepima IV (n = 11), grupo-infección-dieta rica en colesterol-diclofenaco potásico V (n = 9), grupo-infección-dieta rica en -vino tinto VI (n = 8). Se tomaron muestras de sangre de ratas para analizar el colesterol cada mes. Se examinaron secciones de las arterias pulmonares centrales para determinar el grosor de la pared íntima y media mediante análisis computarizado de imágenes. RESULTADOS: Hubo una diferencia estadísticamente significativa en los niveles de colesterol en suero y el grosor de la íntima entre los grupos (p = 0.000). El resto de los grupos tenía más engrosamiento de la íntima que el grupo I (p = 0.000). El grupo III tenía una íntima más gruesa que los grupos IV y V (p = 0,009, p = 0.011 respectivamente). No hubo ninguna diferencia significativa entre los grupos en cuanto al espesor de la media (p = 0.432). CONCLUSIÓN: La infección y la dieta rica en colesterol tienen un efecto sinérgico sobre la aterosclerosis en las arterias pulmonares. Sin embargo, los antibióticos y los agentes antiinflamatorios podrían ser útiles para la prevención.

Use of remifentanil in a patient with eisenmenger syndrome requiring urgent cesarean section

We describe a case of 41 yr old multigravida at 35 weeks gestation, with a diagnosis of Eisenmenger syndrome, requiring urgent Cesarean section. The parturient had signs and symptoms of respiratory distress due to high pulmonary artery pressure, and the pregnancy was complicated by preeclampsia. A general anesthetic consisting of ketamine and etomidate and an intravenous infusion of remifentanil were used to provide stable anesthesia and analgesia for a successful delivery. The baby was delivered with high Apgar scores. The potential benefits and safety of the use of remifentanil in parturients with high pulmonary artery pressures are discussed

Acute hemodynamic effects of sildenafil in patients with idiopathic dilated cardiomyopathy.

Sildenafil, a phosphodiestrase-5 inhibitor, decreases pulmonary artery pressures (PAP) in patients with idiopathic pulmonary hypertension. There is little data pertaining to its use in unselected patients with idiopathic dilated cardiomyopathy (IDCM). A single oral dose of sildenafil (50 mg) was administered to 11 patients (mean age 44.9 +/- 7 years, 7 males) with IDCM with left ventricular ejection fraction < or = 40% in New York Heart Association class II/III at the time of right heart catheterization. There was a significant decrease in pulmonary artery systolic pressure (from 31.5 +/- 9.7 to 19.0 +/- 5.2 mmHg, p < 0.001) and pulmonary vascular resistance (PVR) (from 3.0 +/- 2.1 to 1.6 +/- 0.8 dyne/s/m(2)/cm(5), p = 0.01) following sildenafil administration. The systemic vascular resistance (SVR) and pulmonary wedge capillary pressure also significantly decreased. No significant differences in heart rate, cardiac index and PVR/SVR ratio were observed. There were no side effects documented. Sildenafil produces favorable vasodilation in both pulmonary and systemic vascular beds with decrease in left ventricular filling pressures, in stable patients with IDCM.

Teste de vasorreatividade pulmonar / Testing pulmonary vasoreactivity

A hipertensão arterial pulmonar é classificada como idiopática ou secundária (associada a colagenoses, cardiopatias, hipertensão portal, tromboembolismo pulmonar e doenças da vasculatura pulmonar). O teste de vasorreatividade pulmonar é indicado para definir a melhor opção terapêutica. Muitas drogas têm sido utilizadas para a realização desse teste, sendo o óxido nítrico inalado a melhor opção, por apresentar ação específica pulmonar e meia vida muita curta (5-10 s). O resultado desse teste identifica candidatos à cirurgia cardíaca nas cardiopatias congênitas e candidatos ao uso de antagonista de cálcio nas outras formas de hipertensão pulmonar. A realização e interpretação do teste de vasorreatividade pulmonar exigem grande responsabilidade, e erros podem levar a decisões erradas e à ocorrência de óbitos.

Pulmonary arterial hypertension is classified as idiopathic or secondary (associated with collagenoses, heart disease, portal hypertension, pulmonary thromboembolism, and pulmonary vascular diseases). Pulmonary vasoreactivity should be tested in order to define the best treatment option. Of the many drugs that have been used to test pulmonary vasoreactivity, inhaled nitric oxide is the best choice, due its specific pulmonary effect and very short half-life (5-10 s). The results of this test identify candidates for heart surgery among patients with congenital heart disease and candidates for the use of calcium antagonists among patients with other forms of pulmonary hypertension. Performing and interpreting the results of such tests are a great responsibility, since mistakes can lead to incorrect treatment decisions, resulting in the death of patients.

Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin.

In patients at risk for sudden ethanol (ETOH) intravascular absorption, prompt treatment of pulmonary hypertension (PHTN) will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664) and nitroglycerin (NTG) during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT), as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP), and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7) normal saline, a 500-microg/kg bolus of UK343-664 ( n = 8), or NTG 1 microg/kg ( n = 8); each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP), and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR). Within 2 minutes after treatment with either drug, CVP, heart rate (HR), and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR) ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241+/-579 and 1224+/-494 dyne . cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672+/-308 and 538+/-203 dyne . cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from baseline values of PVR, and the partial recovery of systemic pressure and RV contractility compared to the maximal change during target PHTN, were significant only in the sildenafil analogue group.

A retrospective study of bosentan in pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Pulmonary Arterial Hypertension (PAH) plays a significant role in morbidity and mortality of patients with congenital heart disease (CHD). Bosentan, a dual endothelin receptor antagonist has been approved for PAH patients with Eisenmenger physiology (EP). The authors retrospectively reviewed the efficacy and safety of bosentan in Thai PAH patients associated with CHD. MATERIAL AND METHOD: The study population was obtained from the databases of the CHD patients at Siriraj Hospital from October 2004 to April 2007 who received 6 months of bosentan treatment. Inclusion criteria are: CHD with Eisenmenger physiology (EP) or those with severe PAH after surgical repair or interventional cardiac catheterization. Clinical characteristics including the 6-- minute walk test (6MWT) distances, oxygen saturation (O2 sat), New York Heart Association (NYHA) functional class, and right ventricular systolic pressure (RVSP) at baseline were compared with those at 1, 3, and 6 months post bosentan treatment. Signs and symptoms of adverse events were also recorded. RESULTS: There were 11 patients from among those who fitted the inclusion criteria and whose records were examined. Their average age was 51.1 +/- 10.1 years old (13-61 years old). Patients were divided into 2 groups; Group A (6 patients) was PAH with EP and Group B (5 patients) was PAH post intervention. In group A, the 6MWT increased from 151 +/- 69 meters to 293 +/- 61 meters (p = 0.001) with the average increase of 38 +/- 61 meters. The 2O sat increased from 83 +/- 12.7% to 91.8 +/- 5.6% (p = 0.038) with an average increase of 1.4 +/- 0.07%. There was no significant change in right ventricular systolic pressure (RVSP). In group B, there was a trend in 6MWT improvement from 274 +/- 69 meters to 312 +/- 38 meters but this was not statistically different. There were improvements in the NYHA functional class in both groups. There was no significant increase in serum aminotransferase at the end of 6 months in each patient. CONCLUSION: There are benefits of bosentan for treatment of severe PAH in CHD, especially in patients with Eisenmenger physiology. Obvious benefits are an improvement of 6MWT and O2 sat.

Effects of puerarin on pulmonary vascular remodeling and protein kinase C-alpha in chronic cigarette smoke exposure smoke-exposed rats / 华中科技大学学报（医学）（英德文版）

In order to investigate the effects of puerarin on pulmonary vascular remodeling and protein kinase C-alpha (PKC-alpha) in chronic exposure smoke rats, 54 male Wistar rats were randomly divided into 7 groups: control group (C group), smoke exposure groups (S(4w) group, S(8w) group), puerarin groups (P(4w) group, P(8w) group), propylene glycol control groups (PC(4w) group, PC(8w) group). Rats were exposed to cigarette smoke or air for 4 to 8 weeks. Rats in puerarin groups also received puerarin. To evaluate vascular remodeling, alpha-smooth muscle actin (alpha-SM-actin) staining was used to count the percentage of completely muscularised vessels to intraacinar pulmonary arteries (CMA/IAPA) which was determined by morphometric analysis of histological sections. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were done to detect the PKC-alpha mRNA and protein expression in pulmonary arteries. The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and alpha-SM-actin expression were increased greatly, PASMC apoptosis was increased and proliferation was markedly increased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-alpha mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the percentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-alpha mRNA and protein were lower than in smoke exposure rats. There was no difference among all these data between S groups and PC groups. These findings suggested that cigarette smoke-induced pulmonary vascular remodeling was most likely an effect of the imbalance of PASMC proliferation and apoptosis. Puerarin appears to be able to reduce cell proliferation and vascular remodeling possibly through PKC signaling transduction pathway.

Use of Tadalafil for Treating Pulmonary Arterial Hypertension Secondary to Chronic Obstructive Pulmonary Disease

Pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD) is incurable and it has an unpredictable survival rate. Two men who suffered from COPD presented with progressive dyspnea and edema, respectively. PAH, as estimated by the peak velocity of tricuspidal regurgitation, and the depressed myocardial performance index (MPI) of the right ventricle (RV) were noted on echocardiography. In addition to the baseline therapy for their depressed ventilatory function, we prescribed tadalafil 10 mg orally every other day for 2 weeks and then we doubled the dosage. They well tolerated the medication without any notable side effects. After 4 weeks of tadalafil treatment, the patients' pulmonary arterial pressure was decreased and the MPI of the RV was improved in both. The exercise capacity, as measured by the respiratory oxygen uptake, also improved from 10.9 mL/kg/min to 13.8 mL/kg/min in one patient. We report here on 2 patients with PAH secondary to COPD, and they showed notable improvement of their pulmonary hemodynamics and exercise capacity with the administration of tadalafil.

Effects of oxidizing and reducing agents on ovine pulmonary artery responses to nitric oxide donors, sodium nitroprusside and 3-morpholino-sydnonimine.

Nitrovasodilators-sodium nitroprusside (SNP; 10(-9)-10(-4) M) and 3-morpholino-sydnonimine (SIN-1; 10(-9)-10(-4) M) produced concentration-dependent relaxation of the fourth generation sheep pulmonary artery, preconstricted with 5-hydroxytryptamine (1 microM). Oxidizing agents [oxidized glutathione (GSSG, 1 mM) and CuSO4 (5 and 20 microM)] and reducing agents [dithiothreitol (DTT, 0.1 mM), ascorbic acid (1 mM) and reduced glutathione (GSH, 1 mM)] caused opposite effects on nitric oxide (NO)-induced vasodilation in the artery. Ascorbic acid and GSH potentiated the NO responses, while GSSG and CuSO4 inhibited relaxation caused by the nitrovasodilators. DTT, however, reduced the relaxant potency and efficacy of SNP and SIN-1. Pretreatment of the pulmonary artery strips with DTT (0.1 mM) inhibited SNP (10 microM)-induced Na(+)-K(+)-ATPase activity, while ascorbic acid (1 mM) and GSH (1 mM) had no effect either on basal or SNP (10 microM)-stimulated 86Rb uptake, an index of Na(+)-K(+)-ATPase activity, in ovine pulmonary artery. The results suggest that reducing agents like ascorbic acid may have beneficial effect in improving the vascular function under oxidative stress.

Role of inhaled nitric oxide as a selective pulmonary vasodilator in pediatric cardiac surgical practice.

Our aim was to assess the role of inhaled nitric oxide (NO) therapy in post operative cases of congenital heart defects who developed pulmonary arterial hypertensive (PAH) crisis and had no response with conventional management. From February '95 to January '97, inhaled NO therapy was used in 21 children. Age ranged from 2 months to 9 years (mean 5.6 years) and duration of therapy ranged from 1 to 13 days. Of 21 patients, 17 responded well with 5-20 ppm while 4 did not. The preoperative mean pulmonary systolic pressure was 88 mm Hg against mean systemic pressure of 96 mm Hg. Post operatively, their PA pressure reduced to 62 mm Hg, with systemic pressure of 98 mm Hg. After using inhaled NO, PA pressure dropped to 24 mm Hg (mean systolic) (p < 0.007), after excluding the non responders. Of 4 non responders, two died due to irreversible pulmonary vascular disease and remaining two died due to residual defects. The study shows that inhaled NO is a selective pulmonary vasodilator, which is useful in postoperative PAH crisis and also reduces the transpulmonary gradient in single ventricle repair cases. It is safe and effective for prolonged use. It is very useful in Indian perspective, when more number of cases with congenital heart defects (CHD) along with severe PAH are encountered routinely.

Inhaled nitric oxide and high concentrations of oxygen in pediatrics patients with congenital cardiopathy and pulmonary hypertension: report of five cases

Five patients with ages ranging from 6 months to 3 years were analyzed. All received inhaled nitric oxide (NO - 20 parts per million (ppm)) and oxygen (O2 - at a concentration of 90-95 percent) by means of an oxygen hood. Mean Pulmonary Artery Pressure (MPAP), Mean Aortic Pressure (MAoP), Pulmonary Vascular Resitance (PVR) and Systemic Vascular Resistance (SVR) were measured and the calculation of their relationship to pulmonary/systemic flow (Qp/Qs) was performed by the catheterization of the femoral artery vein. Three patients presented reduction in PVR and increase in Qp/Qs. There were no systemic alterations or any side effect from using NO.