No description available.

Pulmonary arterial hypertension (PAH) is a disease of the lung vessels that causes severe effects on the right ventricle of the heart; ultimately, most patients with severe PAH die as a result of right heart failure. However, little is known about the causes of right heart failure. Here, we describe a pattern of gene expression that differs between the normal rat left ventricle (LV) and right ventricle (RV). These genes are known to be involved in the development of the heart as well as adaptations to the heart during stress. This gene expression pattern is used as a baseline to describe changes in gene expression the occur in the RV as a result of adaptive hypertrophy, stimulated by chronic hypoxia, or right ventricular failure (RVF), caused by administration of Su5416 and hypoxia. The genes differing between RVF and hypertrophy encode glycolytic enzymes, mitochondrial electron transport chain complexes, cell-growth promoting proteins, and angiogenic capillary maintenance proteins. Additionally, we show that RVF is associated with an increase in the serum cytokine production of IL-1 beta, IL-10, TNF-alpha, and VEGF. Finally, we show that treatment with the beta-adrenergic receptor blocker carvedilol partially changed the gene expression pattern seen with RVF. The most profound effects were on the genes encoding glycolytic enzymes and mitochondrial electron transport chain complexes. Together, these results show that the normal LV and RV have a distinct pattern of expression and that the failing RV is characterized by changes in cell growth, angiogenesis, and energy utilization. Treatment with carvedilol can partially reverse these gene expression changes in the failing RV.

Chronic lung diseases are often complicated with pulmonary hypertension (PH). This can lead to disability and poor prognosis. Oxidative stress has been implicated in the development of PH and right ventricular hypertrophy (RVH).A possible new way to treat lung disease related pulmonary hypertension is allopurinol (a xanthine oxidase inhibitor) which decreases both uric acid and oxidative stress. We hypothesised that allopurinol could regress RVH in patients with pulmonary hypertension associated with chronic lung disease (PH-CLD).In a double-blind, randomised controlled clinical trial, 72 patients with PH-CLD (93% diagnosed with chronic obstructive pulmonary disease and 17% with interstitial lung disease) were randomised to receive either allopurinol 300 mg twice daily or placebo for twelve months. The primary outcome was the mean change in right ventricular mass (RVM) as assessed by cardiac magnetic resonance imaging (CMRI) at twelve months. The secondary outcomes were the change in other cardiac parameters measured by CMRI, St George's Respiratory Questionnaire, Short Form 36, spirometry and six-minute walk test (6MWT).The mean age was 71 years, the mean FEV1 was 60% with mean resting SaO2 of 96%. After 12 months, there was no significant change in RVM. There were also no significant changes in other cardiac parameters measured on CMRI, quality of life questionnaires, spirometry and 6MWT. Post-hoc subgroup analysis showed that allopurinol reduced RVM (allopurinol -6.16 g vs placebo 0.75 g, p = 0.02) in COPD patients with more severe airflow limitation. Patients with higher NT-proBNP (> 489 pg/ml) had a greater improvement in left ventricular ejection fraction with allopurinol 5.12 vs placebo -1.62, p = 0.02.In summary, allopurinol had no overall impact but reduced RV mass in COPD patients with more severe airflow limitation. Further studies are warranted to assess the longer term impact of allopurinol in more severe COPD.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

Thesis (MD.) - University of Glasgow, 2007. / MD. thesis submitted to the Faculty of Medicine, Division of Cardiovascular and Medical Sciences, 2007. Includes bibliographical references. Print version also available.

Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-03-12Bitstream added on 2014-06-13T19:42:36Z : No. of bitstreams: 1 serraojunior_nf_dr_botfm.pdf: 386812 bytes, checksum: 797c2c36267c1b3818443412d00ac7ae (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Hipertensão Pulmonar (HP) é definida clinicamente como aumento na pressão vascular pulmonar causada por condições associadas com aumento na pressão arterial pulmonar e/ou venosa. Hemodinamicamente, é definida como aumento na pressão arterial pulmonar média (PAPm) ≥ 25mmHg no repouso, resistência vascular pulmonar (RVP) superior a 4 Unidades Wood, ou quando o gradiente transpulmonar é superior a 10-12 mmHg. Muitos pacientes e clínicos atribuem a dispnéia e fadiga ao descondicionamento físico e à fraqueza muscular global e dos músculos respiratórios, podendo levar o paciente a piora da qualidade de vida. Objetivos: Avaliar a qualidade de vida, a força muscular respiratória (FMR) e a distância percorrida no teste de caminhada de seis minutos (DTC6) em pacientes com hipertensão arterial pulmonar sob tratamento farmacológico específico. Metodologia: Estudo descritivo, prospectivo, série de casos de hipertensão pulmonar em maiores de 18 anos, avaliados no Ambulatório de Hipertensão Pulmonar no período entre fevereiro de 2007 a fevereiro de 2011. Após a consulta médica, foi aplicado o questionário SF-36 para avaliação da qualidade de vida. A seguir, os pacientes foram submetidos à avaliação da força muscular respiratória. Após descanso de 30 minutos, os pacientes realizaram DTC6. Os pacientes foram avaliados em três momentos: M0, sem tratamento farmacológico específico; M1, de dois a quatro meses após tratamento farmacológico específico; e M2, seis meses após M0. Resultados: Havia 16 mulheres e 6 homens, com idade média±DP de 48,46±15,4anos, 21 brancos e 1 não branco, 1 com classe funcional I, 10 com classe funcional II, 9 classe III e 2 classe IV segundo a NYHA modificada para HP. Em relação a qualidade de vida, todos os pacientes avaliados apresentaram... / Pulmonary Hypertension (PH) involves a group of clinical and physiopathological entities with similar characteristics that come from several main diseases. Patients show arterial pulmonary pressure ≥ 25mmHg at rest, pulmonary vascular resistance (PVR) greater than 4 Wood Units, or transpulmonary gradient above 10-12 mmHg. Dyspnea and fatigue are the main symptoms; there is also lack of physical conditioning and global muscle weakness, including respiratory muscles. There are no studies assessing respiratory muscle force (RMF) in this population under specific treatment. Aims: Evaluation of quality of life, RMF and Six Minutes Walk Distance (6MWD) in patients with PH under specific pharmacologic treatment. Patients and Method: This is a descriptive, prospective case series study, of 22 PH patients over 18 years old, from the HC-FMB-UNESP Pulmonary Hypertension Clinic, evaluated at three moments: M0, without specific pharmacologic treatment; M1, two to four months after specific pharmacologic treatment; and M2, six months after M0. In all moments patients were submitted to clinical examination by the physician, RMF was assessed and the 6MWD was performed; then questionnaire SF-36 was applied in order to estimate quality of life. Results: most patients, 16 women and 6 men, average age ± SD 48.5 ± 15.4 years-old, were classified in functional classes II (n=10) and III (n=9) according to NYHA modified for PH. Patients showed improvement in their quality of life, regarding pain (M0 x M2 e M1 x M2), emotional aspect (M0 x M1) and mental health (M0 x M2). As for RMF there was an improvement in maxIP and maxEP (M1 x M2). There was also an improvement in the distance covered in the 6MWD (M0 x M1 and M0 x M2). Correlation between RMF... (Complete abstract click electronic access below)

Background: Inhaled Nitric Oxide (iNO) functions as a selective pulmonary vasodilator. It is an expensive treatment that is often employed as rescue therapy for refractory hypoxaemia in acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT) following cardiac surgery. Objectives: To describe the response to treatment with iNO. Secondary observations were deaths, comorbidities of the patients treated, lengths of treatment and admission, and the cost of treatment. Methods: A retrospective descriptive study of all patients treated with iNO in the Paediatric Intensive Care Unit (PICU) at Red Cross War Memorial Children’s Hospital (RCWMCH) from 2011- 2015. Results: A total of 140 patients were treated with iNO during this time period, 82 were for PHT following cardiac surgery, 53 for ARDS and 5 for PPHN. A response to treatment was observed in 64% of the cohort as a whole, 80% of those with PPHN, 67% of those with PHT post-cardiac surgery, and 64% of those with ARDS. A longer duration of ICU and hospital admission, and higher in hospital mortality (53%) was seen in the group with ARDS, in particular those with adenoviral infection (63%), when compared to patients treated for PHT (18%) and for PPHN (20%). There is no protocol in place guiding the use of iNO in our unit, and it was found that response to treatment was not being objectively measured and documented and that practise varied between clinicians. Conclusions: Considering the cost of treatment and lack of evidence to support beneficial effects of iNO therapy, its continued use in our resource poor setting should be guided by protocol.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: Pulmonary Hypertension (PH) is a devastating disease characterized by pulmonary arterial remodeling, right ventricular dysfunction and ultimately right heart failure. Increased emphasis has been given to skeletal muscle dysfunction in PH, and to its implication in the severe exercise intolerance that is a hallmark of the condition. In this dissertation, skeletal muscle blood flow was measured via the microsphere technique at rest and during exercise (Aim 1), with an acute dose of dietary nitrate via beetroot juice (BRJ) gavage used to determine if supplementation could improve muscle blood flow and alter energetics (Aim 2). VO2max, voluntary running and grip strength tests were used to determine the effect of disease on performance, and to test for an ergogenic effect of BRJ vs. placebo (PL) in healthy and PH rats (Aim 3). Methods: A prospective, randomized, counterbalanced, placebo-controlled trial was used to examine the aforementioned aims across four groups; PH rats (induced with monocrotaline, MCT, 60mg/kg, s.q., 4 weeks) supplemented with BRJ (MCT BRJ, n=9); PH rats supplemented with placebo (MCT PL, n=9); healthy control rats (vehicle, s.q.) supplemented with BRJ (CON BRJ, n=8); healthy control rats supplemented with placebo (CON PL, n=9). Results: Monocrotaline induced a severe PH phenotype evidenced by increased RV wall thickness, RV hypertrophy, RVSP and reduced cardiac output and stroke volume compared to controls (p=<0.001). MCT rats demonstrated lower muscle blood flow at rest, and more prominently during exercise compared to controls (p=0.007-0.047), regardless of supplementation. MCT rats displayed a greater reliance on anaerobic metabolism, demonstrated by increased blood lactate accumulation (p=<0.001), and this was significantly related to reduced blood flow during exercise (r=-0.5879, p=0.001). BRJ supplementation resulted in increased plasma nitrate and nitrite compared to PL (p=<0.001), but at the skeletal muscle level, only nitrate was increased after BRJ. BRJ did not have a significant effect on blood flow, with no improvement during exercise shown vs. PL. Similarly, BRJ did not significantly improve exercise function in MCT or CON rats. Conclusion: MCT rats demonstrated a reduction in muscle blood flow, with BRJ supplementation not resulting in improved flow or exercise performance.

Pulmonary hypertension is becoming a recognized complication of the hereditary and acquired haemolytic anaemias, associated with a poor prognosis. Recently we reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with both right and left ventricular dysfunction and cardiac dysfunction. In the current study we evaluated a cohort of patients (N = 29) with haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac function by Doppler-echocardiography. Of the 29 patients, eight were further studied using cardiac magnetic resonance imaging (MRI), as well as two additional patients (number of patients studied using cardiac MRI = 10). Plasma from the first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12-fold increase in median nitric oxide (NO) consumption when compared with healthy volunteers (P < 0·001). Doppler echocardiography demonstrated normal left ventricular function and elevated pulmonary artery systolic pressure in 41% of patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed right ventricular function in 80% of PNH patients tested, and 60% had findings suggestive of subclinical small pulmonary emboli. Together, these data suggest a high prevalence of haemolysis-associated NO scavenging, Doppler-estimated systolic pulmonary hypertension, and depressed right ventricular function in patients with PNH.