Hypertension Of Different Etiologies Research Articles

Paracentese de alívio no domicílio

Introdução: A ascite é definida como um acúmulo de líquido na cavidade peritoneal e, em 75% dos casos, é causada por cirrose e hipertensão da veia porta de várias etiologias. Seu tratamento inclui restrição de fluidos, diurese e paracentese de grande volume. A paracentese de alívio é o procedimento de remoção de fluido ascítico da cavidade peritoneal com a finalidade de reduzir a pressão intra-abdominal e aliviar sintomas associados como dispneia, dor e desconforto abdominal. É uma técnica simples e segura que pode ser realizada em ambiente hospitalar e ambulatorial. A expansão dos Serviços de Atenção Domiciliar (SAD) no país oportunizou a realização de procedimentos de maior complexidade no domicílio podendo contribuir com o bem-estar de pacientes em cuidado paliativo domiciliar. Objetivo: Descrever o perfil de pacientes submetidos à paracentese de alívio em um SAD. Métodos: Estudo transversal, incluindo pacientes consecutivos que realizaram paracentese de alívio no domicílio entre os anos 2009 e 2017. Os dados foram coletados em prontuário. Para a análise descritiva dos dados estatísticos utilizou-se o Software Statistical Package for the Social Sciences v. 18.0 (SPSS). Resultados: A amostra foi composta por 15 pacientes, apresentando uma média do Índice de Comorbidade de Charlson de 8,1 (3-15). As neoplasias foram as principais causas de ascite nos pacientes acompanhados (80,2%). No período do estudo foram realizadas 48 paracenteses de alívio. Seis pacientes apresentaram sintomatologia clínica com necessidade de visita domiciliar (VD) não programada. Em relação às complicações do procedimento de paracentese, um paciente apresentou sangramento no local da punção. Todas as situações acima foram manejadas no domicílio. Em relação aos desfechos do atendimento no SAD, 53% dos pacientes necessitaram de reinternação hospitalar por piora clínica. Conclusões: A paracentese de alívio no domicílio mostra-se como uma prática segura, reduzindo idas desnecessárias a serviços de urgência/emergência e com bons índices de satisfação relatados pelos pacientes, desde que os profissionais sejam devidamente capacitados para realização do procedimento, com rotina e técnica instituída pelo SAD.

The prognostic value of DLCO and pulmonary blood flow in patients with pulmonary hypertension.

BackgroundCardiac output is a prognostic marker in patients with pulmonary hypertension. Pulmonary blood flow as a surrogate for cardiac output can be measured non-invasively by inert gas rebreathing. We hypothesized that pulmonary blood flow can predict outcome in patients with pulmonary hypertension.MethodsFrom January 2009 to January 2012, we measured pulmonary blood flow by inert gas rebreathing in outpatients with pulmonary hypertension. Patients with pulmonary hypertension confirmed by right heart catheterization and a valid inert gas rebreathing maneuver were followed until January 2016. The investigated outcome was all-cause mortality.ResultsWe included 259 patients (mean age 65 ± 13 years, 53% female) with pulmonary hypertension and classified into groups 1 (n = 103), 2 (n = 26), 3 (n = 80), and 4 (n = 50) according to the current pulmonary hypertension classification system. The median time between pulmonary hypertension diagnosis and inert gas rebreathing was 9 (IQR 0; 36) months. During a median follow-up time of 51 (IQR 20; 68) months, 109 patients (42%) died. Parameters significantly associated with survival (in order of decreasing statistical strength) were diffusion capacity of the lung for carbon monoxide (DLCO), 6-minute walk distance (6-MWD), age, NTpro-BNP, WHO functional class, group 3 pulmonary hypertension, and tricuspid annular plane systolic excursion (TAPSE), while baseline hemodynamics and pulmonary blood flow were not. In multivariable Cox regression analysis, DLCO, age, 6-MWD, and TAPSE remained significant and independent predictors of the outcome. DLCO as the strongest parameter also significantly predicted survival in aetiological subgroups except for group 4.ConclusionsDLCO is a strong and independent predictor for survival in patients with pulmonary hypertension of different aetiologies, while pulmonary blood flow measured by inert gas rebreathing is not.

Comparative evaluation of CacyBP/SIP protein, β-catenin, and immunoproteasome subunit LMP7 in the heart of rats with hypertension of different etiology.

Despite extensive research into the pathogenesis of hypertension and disease-related end organ damage, the mechanisms leading to cardiac complications of hypertensive patients are still not fully elucidated. The aim of the presented research was immunodetection and evaluation of CacyBP/SIP, β-catenin, and proteasomes in the hearts of rats with hypertension of different etiology. Our results show an innovative and important network of interactions between proteins potentially involved in the development and progression of heart problems in various types of hypertension. This report might contribute to deeper understanding of the role of the CacyBP/SIP protein, β-catenin, and proteasomes in heart function. Our results might also bring new information concerning the intracellular processes and signal pathways involved in the regulation of cardiomyocytes functioning in hypertension state. In addition to cognitive significance, the results of presented studies may contribute to further successes in preventing and treatment of cardiac complications associated with hypertension.

Quantitative characteristics of the neurotensin content in the hypothalamic arcuate nucleus in arterial hypertension of different etiologies

The aim of this work is to determine the features of the neurotensin content in the hypothalamic ARC in Wistar rat and SHR strains in arterial hypertension of different etiology: endocrine-salt and essential. Materials and methods . The study was performed on 24 adult male rats at the age of 13–14 months, weight of 250–270 g, which were divided into three experimental groups of 8 animals each. The 1 st group (control) – Wistar rats with normal BP indices (Psys / Pdias = 110/75 ± 5 mm Hg), the 2 nd – Wistar rats with endocrine-salt model of hypertension (Psys/Pdias = 145/110 ± 10 mm Hg); the 3 rd – SHR with spontaneous arterial hypertension (Psys/Pdias = 150/110 ± 10 mm Hg). An immunohistochemical method was used to study the content of neurotensin in the arcuate nucleus, analyzed by digital processing with Image J and EXCEL-7.0. Results . Persistent increase in BP is accompanied by an increase in the content and concentration of neurotensin in the hypothalamic ARC, does not depend on the etiology of hypertension and has a compensatory character. In SHR with essential hypertension there is a higher expression of neurotensin in the hypothalamic ARC in comparison with the endocrine-salt model of hypertension, but the number of neurons involved in the synthesis and accumulation of the neurohormone is significantly lower, which characterizes the morphological features of cellular populations in the hypothalamus of the animals of this strain and can play a role in the development and progression of hypertension.

The Effect of Epicardial Fat on the Right and Left Ventricular Function in Subjects with Various Etiological Types of Pulmonary Arterial Hypertension

Abstract Background: Little is known on the effect of epicardial fat in pulmonary arterial hypertension (PAH). Therefore, the present study sought to perform a comparative analysis on the influence of epicar-dial fat thickness (EFT) on the right and left ventricular function, between three different etiological varieties of pulmonary arterial hypertension: caused by congenital heart defects (atrial septum defects with left to right shunt), by systemic sclerosis, and by myocardial ischemia. Materials and Methods: This is a prospective observational study on 50 patients with documented PAH (systolic pulmonary artery pressure – PASP of >35 mmHg). The thickness of the epicardial adipose tissue was evaluated by 2D cardiac ultrasound, on the free wall of the right ventricle, during end-diastole, in the long parasternal axis view. The patients were divided into three study groups: Group 1 – PAH determined by congenital heart defects with left to right shunts (atrial septum defects, n = 25); Group 2 – PAH induced by systemic sclerosis (n = 12); Group 3 – PAH induced by myocardial ischemia (n = 13). Results: The average age was 54.48 ± 10.78 years, 30% (n = 15) of subjects were males, with a mean body mass index of 24.65 ± 4.40 kg/m2, EFT was 9.15 ± 2.24 mm, and the PASP was 41.33 ± 5.11 mmHg. Patients in Group 3 were more likely to smoke (p = 0.025) and presented a significantly lower LVEF, compared to the other groups (Group 1: 60% ± 6 vs. Group 2: 60% ± 7 vs. Group 3: 48% ± 7, p <0.0001). The largest EFT was found in Group 3 (11.08 ± 2.39 mm), followed by Group 2 (9.14 ± 2.03 mm), and Group 1 (8.16 ± 1.57 mm) (p = 0.0003). The linear regression analysis found no significant correlations between EFT and other echocardiographic parameters: PASP (r = −0.228, p = 0.118), LVEF (r = −0.265, p = 0.06), TAPSW (r = 0.015, p = 0.912), TEI (r = 0.085, p = 0.552), RVEDD (r = −0.195, p = 0.173), RA area (r = −178, p = 0.214), and LA diameter (r = 0.065, p = 0.650). Conclusions: Epicardial fat thickness was found to be significantly higher in patients with PAH induced by myocardial ischemia, followed by those with systemic sclerosis and congenital heart defects, respectively. EFT did not influence the echocardiographic parameters for left and right ventricular function in patients with pulmonary arterial hypertension of different etiologies.

THE EFFICACY OF SILDENAFIL THERAPY IN PATIENTS WITH PULMONARY HYPERTENSION OF DIFFERENT ETIOLOGY: INFLUENCE ON THE CLINICAL, FUNCTIONAL, HEMODYNAMIC STATUS, STRUCTURE AND FUNCTION OF THE RIGHT AND LEFT HEART, RIGHT VENTRICULAR-ARTERIAL COUPLING

Aim: to study the efficacy of sildenafil therapy in pulmonary hypertension of different etiology, its influence on the clinical, functional, hemodynamic status, structure and function of the right and left heart, right ventricular-arterial coupling (RVAC) in pts with idiopathic pulmonary hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH).Materials and methods: in the study we included 29 IPAH pts aged 42.8±10.6 yrs, 28 CTEPH pts aged 43.4±10.4 yrs II-IV functional class (FC) (WHO), receiving stable standard therapy (anticoagulants, diuretics, glycosides) and calcium channel blockers for at least 3 months. Sildenafil was started at the dose of 10 mg TID to assess the tolerability for further titration after 1 wk to 20 mg 3 times a day. The treatment duration was 16 wks. At baseline and at wk 16 FC (WHO), 6-minute walking test (6-MWT), transthoracic echocardiography (Echo) and right heart catheterization (RHC) were performed.Results: both groups were comparable in baseline functional parameters: FC, the distance in 6-MWT, Borg index. The analysis of baseline structural and functional cardiac parameters by Echo in IPAH and CTEPH pts revealed pronounced cardiac remodeling as compared to the control group. All pts had criteria precapillary PH by RHC with comparable systolic pulmonary artery pressure (SPAP), mean pulmonary artery pressure (PAPm), cardiac output (CO) and index (CI), pulmonary vascular resistance (PVR) except for diastolic PAP (DPAP), which was higher in IPAH group (38.3±13.7 mm Hg vs 31.5±8.9 mm Hg in CTEPH group (p<0.05). Sildenafil therapy resulted in the marked improvement of functional and hemodynamic status, cardiac remodeling parameters in both groups. To wk 16 IPAH pts achieved the 114m increase in 6-MWT as compared with 108m in CTEPH group. IPAH pts demonstrated the significant decrease in SPAP, PAPm, reduce of right ventricular (RV) size and improvement of contractile function - FAC and TAPSE, increase of RVAC by reducing LV stiffness. Eccentricity index of LV improved significantly only in CTEPH pts. Positive dynamic in RHC data (significant decrease of SPAP, PAPm, DPAP, PVR, increase of CO,CI, stroke volume). CTEPH pts showed a greater reduction in PVR, SPAP and significant SvO2 improvement.Conclusion: 1. In pts with IPAH and CTEPH of comparable baseline clinical, functional and hemodynamic status we found no significant differences in the severity of cardiac remodeling, RV and LV systolic and diastolic function. Regardless of etiology RVAC was reduced due to the significant increase of LV stiffnessEs. 2. 16-wk sildenafil therapy in pts with IPAH and CTEPH resulted in the positive dynamic of 6-MWT distance, dyspnea index, Echo data including LV stiffness. 3. In CTEPH group as compared with IPAH pts we found the more marked reduction in PVR, PASP and significant improvement SvO2 by RHC. The significant decrease in Es was observed only in CTEPH pts.

Features of cutaneous microcirculatory blood flow in patients with pulmonary hypertension of different etiology

Aim: to evaluate features of the functional state of microvascular bed of the skin in patients with pulmonary arterial hypertension associated to congenital cardiac disease (PAH-CCD) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods. In study included 25 patients (41.6±15.8) with PAH-CCD, 25 patients (48.8±14.2) with CTEPH and 25 healthy volunteers (39.3±10.1 years). All the patients underwent a six-minute walking test (6-MWT), transthoracic echocardiography, thorax organs radiography, right heart catheterization (RHC) and Laser Doppler flowmetry (LDF) with amplitude and frequency wavelet analysis of blood flow oscillations and evaluation of constrictory and dilatatoryskin resistive microvesselsfunctions. Results. In the PAH-CCD in relation to the CTEPH groupaccording to the RHC were noted significantly higher values of systolic pressure in pulmonary artery (93.2 and 77.8 mm Hg respectively) and venous mixted blood saturation(63 and 57% Hg respectively). On this background 6- MWT distance was 356 and 325 m, the Borg dyspnea scale index was on average 3.12 and 3.76 respectively. According to the LDF pulseoximetry PAH-CCD and CTEPH patients had 90.1 and 94.7% respectively. According to the LDF with amplitude and frequency wavelet analysis the PAH-CCD patients had sig-nificantly higher values of the amplitude of myogenic, respiratory and pulse sectionof blood flow modulation, and also increased constrictory activity smooth muscle cells of skin precapillary arterioles in response to the stretching at venous occlusion and decreased dilatatory reserve at post-occlusi-ve reactive hyperemia. According to the LDF the CTEPH patients had elongationof time development of microvessel constriction in response to acti-vation of sympathetic nervous systemin respiratory and cold tests. Conclusion. According to the LDF functional state of skin microvessels in systemic circulation of the CTEPH patients was comparable with control groupexcept for elongation of time development of microvessel reactions for sympathetic vasoconstrictor stimulations. The PAH-CCD patients demonstrated basal tonus decreasing of smooth muscle cells of skin precapillary arterioles in systemic circulation, which can be regarded as a manifestation of autoregulatory response to systemic hypoxia.

CRT-500.01 Hemodynamic, Functional, and Clinical Responses to Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension of Different Etiologies: Phase II Results From the PADN-1 Study

The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of

CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone

Although sensitivity to high dietary NaCl is regarded to be a risk factor for cardiovascular disease, the causes of salt-sensitive hypertension remain elusive. Previously, we have shown that rats pretreated with subpressor doses of either ANG II or aldosterone (Aldo) show sensitized hypertensive responses to a mild pressor dose of ANG II when tested after an intervening delay. The current studies investigated whether such treatments will induce salt sensitivity. In studies employing an induction-delay-expression experimental design, male rats were instrumented for chronic mean arterial pressure (MAP) recording. In separate experiments, ANG II, Aldo, or vehicle was delivered either subcutaneously or intracerebroventricularly during the induction. There were no sustained differences in BP during the delay prior to being given 2% saline. While consuming 2% saline during the expression, both ANG II- and Aldo-pretreated rats showed significantly greater hypertension. When hexamethonium was used to assess autonomic control of MAP, no differences in the decrease of MAP in response to ganglionic blockade were detected during the induction. However, during the expression, the fall was greater in sensitized rats. In separate experiments, brain tissue that was collected at the end of delay showed increases in message or activation of putative markers of neuroplasticity (i.e., brain-derived neurotrophic factor, p38 mitogen-activated protein kinase, and cAMP response element-binding protein). These experiments demonstrate that prior administration of nonpressor doses of either ANG II or Aldo will induce salt sensitivity. Collectively, our findings indicate that treatment with subpressor doses of ANG II and Aldo initiate central neuroplastic changes that are involved in hypertension of different etiologies.

Organised right ventricular remodelling in aortic stenosis even after valve replacement

Organised right ventricular remodelling in aortic stenosis even after valve replacement

Prognostic Value of Right Ventricular Longitudinal Peak Systolic Strain in Patients With Pulmonary Hypertension

Right ventricular (RV) function is an important prognostic marker in patients with pulmonary hypertension. The present evaluation assessed the prognostic value of RV longitudinal peak systolic strain (LPSS) in patients with pulmonary hypertension. A total of 150 patients with pulmonary hypertension of different etiologies (mean age, 59±15 years; 37.3% male) were evaluated. RV fractional area change and tricuspid annular plane systolic excursion index were evaluated with 2-dimensional echocardiography. RV LPSS was assessed with speckle-tracking echocardiography. The patient population was categorized according to a RV LPSS value of -19%. Among several clinical and echocardiographic parameters, the significant determinants of all-cause mortality were evaluated. There were no significant differences in age, sex, pulmonary hypertension cause and left ventricular ejection fraction between patients with RV LPSS <-19% and patients with RV LPSS ≥-19%. However, patients with RV LPSS ≥-19% had significantly worse New York Heart Association functional class (2.7±0.6 versus 2.3±0.8; P=0.003) and lower tricuspid annular plane systolic excursion (16±4 mm versus 18±3 mm; P<0.001) than their counterparts. During a median follow-up of 2.6 years, 37 patients died. RV LPSS was a significant determinant of all-cause mortality (HR, 3.40; 95% CI, 1.19-9.72; P=0.02). In patients with pulmonary hypertension, RV LPSS is significantly associated with all-cause mortality. RV LPSS may be a valuable parameter for risk stratification of these patients. Future studies are needed to confirm these results in the pulmonary hypertension subgroups.

Distribution of endothelin-1 in the lung of rats with pulmonary hypertension of different etiology

Endothelin (ET)-1 is a potent vasoconstrictor peptide and induces vascular smooth muscle cell proliferation. We previously reported that an ET receptor antagonist prevented the progression of pulmonary hypertension (PH) caused by inflammatory lung disease in rats. The aim of the present study was to investigate whether pathophysiological roles of endogenous ET-1 in PH caused by congestive heart failure (CHF) differ from PH caused by inflammatory lung disease. For this purpose, we investigated the distribution of ET-1 staining (ET-1-like immunoreactivity) by the immunohistochemical method using an anti-ET-1 antibody in the lungs of rats with PH due to CHF or inflammatory lung disease. CHF was surgically induced by permanent left coronary arterial ligation in rats. At 2 weeks after the surgery in rats, left ventricular contractility (LV+dP/dtmax) was decreased, whereas right ventricular systolic pressure was increased, indicating that the rats developed CHF accompanied by PH. The intensity of ET-1 staining was stronger in the pulmonary vascular endothelial cells of the CHF rats than that of the sham-operated rats. We used monocrotaline (MCT)-induced PH rats (MCT rats) as a model of PH due to inflammatory lung disease. Three weeks after MCT injection, the MCT rats developed PH. The intensity of ET-1 staining in the pulmonary vascular endothelial cells of the MCT rats did not differ from that of the control rats, however, the intensity of the ET-1 staining in the MCT rats was increased in the alveolar walls (especially in macrophages). These data show that the distribution of ET-1 staining in the lungs of the rats with PH due to CHF differs from that of the rats with PH due to inflammatory lung disease.

Intravenous epoprostenol versus high dose inhaled iloprost for long-term treatment of pulmonary hypertension

Background Intravenous prostacyclin (iv PGI) and inhaled Iloprost (inh ilo) are established therapies in pulmonary arterial hypertension (PAH), however comparative data are lacking. Methods and patients We performed a long-term open label comparison trial of iv PGI or high dose inh ilo in 24 patients with severe PAH: 12 patients (9 female, 40 +/− 14 years, 10 idiopathic PAH, 2 PAH in connective tissue disease CTD) received iv PGI, whereas 12 patients (7 female, 43 +/− 12 years, 5 IPAH, 6 CTD, 1 porto-pulmonary hypertension) were commenced on inh ilo with a median dose of 120 μg/24 h. Haemodynamic parameters and 6 min walking distance (6MWD) at baseline did not differ between both groups. Results After 3 months therapy, patients on iv PGI showed a significant increase in 6MWD from 220 to 280 m ( p < 0.01), whereas patients on high dose inh ilo increased 6MWD from 200 to 275 m ( p < 0.05). The event free follow up was 23 [1–76] months in the iv PGI2I group, and 16 [7–38] months in the high dose inh ilo group ( p < 0.05). Patients with a 6MWD ≥ 300 m after 3 months therapy had a significantly longer event free follow up [16 vs. 35 months; p < 0.004]. Conclusion In this patient population with severe pulmonary hypertension of different etiologies, event free follow up on treatment with iv PGI is significantly longer compared to high dose inh ilo. The 6MWD after 3 months treatment might be predictive for long term outcome.

Pleuropulmonary complications of esophageal variceal sclerotherapy with absolute alcohol.

Esophageal variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage. However, it causes a wide variety of local and systemic complications. The present study was performed to document pleuropulmonary complications of EVS with absolute alcohol. Twenty-six patients of portal hypertension of different etiologies were subjected to EVS with absolute alcohol. Baseline arterial blood gas analysis (PaO2, PaCO2, pH, HCO3, SaO2), chest X-ray and pulmonary function tests (forced expiratory volume at 1 s (FEV1), forced expiratory vital capacity (FVC), FEV1/FVC, maximum mid-expiratory flow rate (MMFR), and peak expiratory flow rate (PEFR)) were performed 4-6 h before the first session of EVS. These investigations were repeated within 24 h of EVS. Patients were asked to maintain a symptom diary and to record symptoms such as fever, chest pain, dysphagia and dyspnea during the study period. Ten patients (38.46%) had chest pain and four patients (15.68%) had fever after sclerotherapy. Eight patients (30.54%) complained of dyspnea and six patients (23.08%) developed pleural effusion. There was a significant decline in FVC and FEV1 after EVS as compared with baseline values. However, FEV1/FVC ratio, MMFR and PEFR did not have any significant change. Chest pain (38.46%), dyspnea (30.54%) and fever (15.68%) were the common symptoms after EVS while chest X-ray showed pleural effusion in 23.08%. Pulmonary function tests revealed a significant decline in FEV1 and FVC without change in FEV1/FVC ratio after EVS, suggesting a restrictive type of defect.

NT-proANP and BNP in Renovascular and in Severe and Mild Essential Hypertension

Background/Aims: The plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) become increased in hypertension. However, it is unknown what is the effect of the etiology and the severity of hypertension on the plasma concentrations of ANP and BNP. Methods: We examined plasma levels of ANP (measured as N-terminal fragment of proatrial natriuretic peptide; NT-proANP) and BNP in patients having sustained hypertension of different etiology and severity: in patients with renovascular hypertension (RVHT, n = 12), severe essential hypertension (SEHT, n = 37), and mild essential hypertension (MEHT, n = 29). In addition, we studied the diagnostic value of NT-proANP and BNP to discriminate patients with RVHT from patients with essential hypertension. Results: The plasma concentrations of NT-proANP and BNP were higher in the RVHT group (593 ± 80 and 25.0 ± 9.3 pmol/l, respectively) than in the SEHT group (320 ± 33 and 4.7 + 0.6 pmol/l, respectively; p < 0.001 for both), in spite of the similar blood pressure level, and also higher than in the MEHT group (356 ± 30 and 7.0 ± 1.0 pmol/l; p = 0.004 and p = 0.006, respectively). There was no difference in natriuretic peptide levels between the SEHT and MEHT groups. Plasma NT-proANP and BNP correlated positively with aging and serum creatinine concentration and inversely with left ventricular diastolic filling. In addition, NT-proANP correlated positively with systolic blood pressure and BNP with left ventricular mass index. The areas under receiver operating characteristic curves for plasma NT-proANP and BNP to discriminate RVHT patients from patients with essential hypertension were 0.793 and 0.782, respectively. The best cutoff value was 530 pmol/l for NT-proANP, giving a sensitivity of 67% with a specificity of 86%. The cutoff value of 9.8 pmol/l for BNP resulted in a sensitivity of 58% and a specificity of 90%. Conclusions: Patients with RVHT have higher plasma levels of NT-proANP and BNP than patients with essential hypertension. In addition to the etiology of hypertension, also left ventricular characteristics are important determinants of NT-proANP and BNP concentrations in hypertension. Due to the low sensitivity, NT-proANP and BNP are not suitable as screening tools for RVHT.

Reversible brain lesions in childhood hypertension

Posterior leukoencephalopathy syndrome is characterized by an acute, usually reversible, encephalopathy with transient occipital lobe abnormalities detected on MRI that occur mostly in association with acute hypertension. The clinical presentation includes seizures, headache, altered mental status and blindness. Disturbed autoregulation of cerebral blood flow and endothelial injury are central to the pathogenesis of this disorder. Prompt control of hypertension results in rapid and complete neurological recovery. In this report we discuss the cases of two children with acute onset hypertension of different aetiologies that presented with the characteristic features of posterior leukoencephalopathy syndrome. Conclusion: Early recognition of this readily treatable condition may obviate the need for extensive and invasive investigations. Despite the alarming lesions on the MRI, prompt control of hypertension carries a uniformly favourable prognosis.

Pathobiology of pulmonary hypertension in infants and children

Pulmonary vascular disease occurs as a rare primary disorder and a common, frequently major complication of many disease states. But we still cannot define the stimuli and signal transduction pathways which instigate and perpetuate the disease state, and therefore our treatment strategies are reactive, nor proactive. Observational studies on patients with pulmonary hypertension of different aetiologies have identified potentially important structural and functional abnormalities, but whether these are a cause or a consequence of the disease process remains to be determined. Recent genetic studies indicate, for the first time, a primary abnormality in the regulation of pulmonary vascular remodelling in a sub-set of patients with pulmonary hypertension. The aim of research in pathobiology is to discover the molecular mechanisms responsible for the complex vascular changes associated with pulmonary hypertension and in doing so, improve treatment strategies.

Distribution of endothelin-1 in the lung of rats with pulmonary hypertension of different etiology

Endothelin (ET)-1 is a potent vasoconstrictor peptide and induces vascular smooth muscle cell proliferation. We previously reported that an ET receptor antagonist prevented the progression of pulmonary hypertension (PH) caused by inflammatory lung disease in rats. The aim of the present study was to investigate whether pathophysiological roles of endogenous ET-1 in PH caused by congestive heart failure (CHF) differ from PH caused by inflammatory lung disease. For this purpose, we investigated the distribution of ET-1 staining (ET-1-like immunoreactivity) by the immunohistochemical method using an anti-ET-1 antibody in the lungs of rats with PH due to CHF or inflammatory lung disease. CHF was surgically induced by permanent left coronary arterial ligation in rats. At 2 weeks after the surgery in rats, left ventricular contractility (LV+dP/dtmax) was decreased, whereas right ventricular systolic pressure was increased, indicating that the rats developed CHF accompanied by PH. The intensity of ET-1 staining was stronger in the pulmonary vascular endothelial cells of the CHF rats than that of the sham-operated rats. We used monocrotaline (MCT)-induced PH rats (MCT rats) as a model of PH due to inflammatory lung disease. Three weeks after MCT injection, the MCT rats developed PH. The intensity of ET-1 staining in the pulmonary vascular endothelial cells of the MCT rats did not differ from that of the control rats, however, the intensity of the ET-1 staining in the MCT rats was increased in the alveolar walls (especially in macrophages). These data show that the distribution of ET-1 staining in the lungs of the rats with PH due to CHF differs from that of the rats with PH due to inflammatory lung disease.

Distribution of Endothelin-1 in the Lung of Rats With Pulmonary Hypertension of Different Etiology

Endothelin (ET)-1 is a potent vasoconstrictor peptide and induces vascular smooth muscle cell proliferation. We previously reported that an ET receptor antagonist prevented the progression of pulmonary hypertension (PH) caused by inflammatory lung disease in rats. The aim of the present study was to investigate whether pathophysiological roles of endogenous ET-1 in PH caused by congestive heart failure (CHF) differ from PH caused by inflammatory lung disease. For this purpose, we investigated the distribution of ET-1 staining (ET-1-like immunoreactivity) by the immunohistochemical method using an anti-ET-1 antibody in the lungs of rats with PH due to CHF or inflammatory lung disease. CHF was surgically induced by permanent left coronary arterial ligation in rats. At 2 weeks after the surgery in rats, left ventricular contractility (LV+dP/dtmax) was decreased, whereas right ventricular systolic pressure was increased, indicating that the rats developed CHF accompanied by PH. The intensity of ET-1 staining was stronger in the pulmonary vascular endothelial cells of the CHF rats than that of the sham-operated rats. We used monocrotaline (MCT)-induced PH rats (MCT rats) as a model of PH due to inflammatory lung disease. Three weeks after MCT injection, the MCT rats developed PH. The intensity of ET-1 staining in the pulmonary vascular endothelial cells of the MCT rats did not differ from that of the control rats, however, the intensity of the ET-1 staining in the MCT rats was increased in the alveolar walls (especially in macrophages). These data show that the distribution of ET-1 staining in the lungs of the rats with PH due to CHF differs from that of the rats with PH due to inflammatory lung disease.

In vitro study of the formation of NO2 in inhalation of nitrogen monoxide

Nitric oxide (NO), an endogenous endothelium-derived relaxing factor, produces profound relaxation of vascular smooth muscle. Thus, inhaled NO is a potent and selective pulmonary vasodilator that may be useful for treatment of pulmonary hypertension of different aetiologies. However, the main danger of NO inhalation is spontaneous formation of toxic nitrogen dioxide (NO2) if NO is added to an oxygen-containing gas mixture. This chemical reaction depends on the time available for the oxidation and the concentration of NO and oxygen. The aim of this study was to assess in vitro the spontaneous formation of NO2 during administration of various NO concentrations with a ventilator. A modified ventilator system is described which can deliver NO within clinically relevant concentrations avoiding excessive formation of toxic NO2. The system was evaluated using an artificial lung. NO and NO2 concentrations were measured by chemiluminescence at the proximal and distal end of the inspiratory limb. In-vitro NO2 formation was assessed during administration of 10, 20, 40, 80 ppm NO while ventilating with an FiO2 of 0.25, 0.5 and 0.75, an inspiratory minute volume of 5, 7.5 and 10 l/min (IMV) and a respiratory rate of 12/min. NO2 concentration correlated with increasing FiO2 and NO concentration and was inversely correlated to IMV. While ventilating with 5-40 ppm NO, an FiO2 of 0.25-0.75 and an IMV of 10 l per minute, the NO2 formation was measured to be less than 0.2 ppm and thus not clinically relevant. During administration of 80 ppm NO the NO2 formation increased to 0.3-0.6 ppm. We conclude that for patients safety concentrations less than 80 ppm of inhaled NO should be used with this ventilator system. In addition, online monitoring of the NO2 concentration in the inspiratory limb should always be performed.