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Volumen 5, Asunto 5 (2015)

Artículo de revisión

Genetic Variations in Renin-Angiotensin-Aldosterone System (RAAS) Genes Could Contribute to High Altitude Pulmonary Edema: Review

Swati Srivastava

Background: At High Altitude (HA) (elevation >2500m), inevitable hypobaric hypoxia leads to development of symptoms associated with low oxygen pressure in many non acclimatized sojourners which includes severe forms of altitude mountain sickness (AMS) such as high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). These syndromes are reportedly less common in high altitude native population than in lowlanders which can be attributed to genetic adaptations that have taken place over generations.

Methods: Numerous genetic studies have been associated with hypoxic adaptation and susceptibility to high altitude conditions. An increased pulmonary arterial pressure (PAP) and fluid loss has been observed in all forms of AMS with varied intensity. Since renin-angiotensin-aldosterone system (RAAS) has a critical function of maintaining homeostasis in closed circulatory system, the polymorphisms occurring in the genes of RAAS pathway could likely be contributing towards acclimatization/mal-adaptation to high altitude maladies. In view of above, this review has been compiled to associate the genetic variations in RAAS with adaptation/acclimatization to high altitude conditions.

Results: Studies conducted so far relate allele frequencies of polymorphic loci in genes encoding components of RAAS pathway such as angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin receptors (AT1) and aldosterone synthase (CYP11B2) and associate them with hypertension, regulation of blood pressure and maintenance of osmotic balance in the body.

Conclusions: In this review, various studies have been put together comprehensively indicating the involvement of genetic variants of RAAS genes in resistance or sensitivity of an individual towards development of HAPE.

Artículo de investigación

Circulating Aldosterone Levels and Disease Severity in Pulmonary Arterial Hypertension

Zeenat Safdar, Aishwarya Thakur, Supriya Singh, Yingqun Ji, Danielle Guffey, Charles G Minard and Mark L Entman

Objectives: It is not known whether aldosterone levels are associated with increased mortality in patients with pulmonary arterial hypertension (PAH). The primary goal of this study was to determine whether circulating aldosterone levels predict severity of PAH in terms of hemodynamic characteristics and mortality.

Methods: Patients with stable PAH were enrolled at the Baylor PH program. The plasma levels of aldosterone and BNP were measured. Clinical, hemodynamic, and outcome data was collected by chart review. Mean follow up time from study enrollment was 39 ± 102 months. Cox proportional hazards model was used to assess time to death.

Results: There were 125 PAH patients with plasma aldosterone levels. Median aldosterone level was 9.9 pg/ml (25th-75th percentile: 4.1 pg/ml, 27.1 pg/ml) and median brain natriuretic peptide (BNP) level was 67.5 pg/ml (25th- 75th percentile: 31 pg/ml, 225 pg/ml). Aldosterone levels were not significantly associated with BNP levels, six-minute walk distance, Borg dyspnea score, right ventricular systolic pressure, cardiac output and cardiac index. However, the association between aldosterone and right atrial pressure was dependent on mineralocorticoid receptor blocker treatment (Coef.=2.88, 95CI: 1.19, 4.56, p=0.001). By log-rank statistic there was no statistical difference between the survival of patients divided by median aldosterone level (p=0.914). However, there was a significant difference in patient survival between the BNP categories (p<0.001) such that those with high BNP level (>180 pg/mL) had a shorter survival time.

conclusions: The aldosterone level was not associated with increased mortality in PAH but was a marker of disease severity.

Artículo de investigación

Detection of Smoking Induced Emphysema: Visual Scoring versus Computerised Algorithms

Martin Anderson, Gunnar Engström, Lars H Nordenmark, Dag Mohlkert, Elmira Rouzbeh, Maria Gerhardsson de Verdier, Ulf Nihlén, Thomas Fehniger, Magnus Dahlbäck and Magnus Svartengren

Purpose: Computed tomography (CT) has been applied to assess signs of early disease in a population study. Comparisons were made of histogram based methods to quantitatively determine lung density; relative area of emphysema below -910 and -950 Hounsfield units, and 15th percentile density (RA -910, RA -950 and PD15), as well as visual assessment of computed tomography (CT) images, to lung function indices in a population based study of smokers and non-smokers.

Methods: 138 subjects from a study of lung function in COPD were included in the study. Computerised assessments and visual scoring were used to analyse CT scans of different regions of identifying subjects with emphysema.

Results: Subjects visually diagnosed with centrilobular emphysema had significantly lower lung density (n=27, PD15=-932 HU, RA-950=6.6%) compared to subjects without emphysema (n=106, PD15=-917 HU, RA-950=2.3%). In the group with low PD15, the proportion with visually determined centrilobular emphysema was 38%, compared to 15% in the groups with high PD15.

Conclusion: Evaluation of patterns of lung attenuation by automated assessment and visual scoring provided similar classifications of disease in patients with mild COPD but differed in identifying regions of low density in healthy subjects. Visual assessment showed better correlation to both lung function and smoking habits than quantitative measures in this study. Quantitative measures should be used in the upper third of the lungs to detect smoking induced emphysema. Measurements of early attenuation changes within healthy subjects may require additional measures of validation by radiologists by visual assessment.

Artículo de investigación

Pre-Operative Use of Aspirin May Reduce Atrial Fibrillation Development Rate during Coronary Bypass Surgery

Oruc Alper Onk, Eyup Serhat Calik, Umit Kahraman, Osman Nuri Tuncer, Serif Yurt, Ozgur Dag and Bilgehan Erkut

Objective: We sought to determine whether the administration of aspirin reduces the incidence of postoperative atrial fibrillation in coronary arterial bypass grafting surgery. Atrial fibrillation leads to an increase in morbidity and mortality as well as a increase in length of hospital stay due to an excess of medication usage.

Methods: From January 2012-May 2015, 550 patients undergoing coronary artery bypass surgery at our hospital were randomly assigned to two groups-treatment and control. In the treatment therapy group, the patients took acetylsalicylic acid (300 mg) without stopping before coronary bypass surgery. In the control group, the patients did not receive any anti-aggregant therapy before surgery. The rate of atrial fibrillation was retrospectivel evaluated between first 3 days, one week, and 4 weeks after surgery.

Results: While atrial fibrillation developed in 14 patients (5.1%) in treatment group, this rate was 24.2% with 68 patients in control group 4 weeks after operation (p<0.05). Between the groups there was an significant difference in terms of intensive care unit and hospital stay. In the treatment group, the ICU and hospital stay was shorter compared with the other group (p<0.05). Hospital charges were less in the treatment group (p<0.05).

Conclusion: These results suggest that aspirin is a useful drug for prevention of atrial fibrillation. Besides, aspirin treatment until operation day reduces hospital costs and length of stay in hospital, after the coronary artery bypasses grafting.

Artículo de investigación

Bronchial Thermoplasty by Application of Ultrasound Energy

Lidia Sobkow, Sajive Aleyas, Matthew Pollman, Dong Ik Shin, Joerg Schulze-Clewing, Tom Zimmerman, Valery Matthys, Jean Rooney, Li Liu and Reinhard J. Warnking

Background: Asthma is a chronic inflammatory disease of respiratory airways, typically marked by spasms in the bronchi of the lungs, causing difficulty in breathing. Although the disease is very well documented, therapies are limited and patients mostly undergo symptom management. Bronchial thermoplasty is a radiofrequency-based treatment for severe asthma approved by Food and Drug Administration (FDA) in 2010 (Alair system, Boston Scientific Inc). Here we propose the use of ultrasound (US) energy to perform bronchial thermoplasty. Our hypothesis is that ultrasound affects bronchial smooth muscle at least as effective as radio-frequency (RF) but causes less collateral damage, and holds the potential to reduce the procedure time. In this publication we present a direct comparison of acute thermoplasty effects of RF energy versus ultrasound energy.

Objective: To evaluate a bronchoscopic procedure based on circumferential ultrasound energy and its effect on bronchial wall structures in comparison to RF thermoplasty for asthma treatment.

Methods: This is an observational study aiming for a direct comparison of an ultrasound system with existing asthma therapy based on radio-frequency. Mongrel dogs were used for optimization of ultrasound energy (300 J, 200 J, 100 J) with a 4.5 and 5.5 mm balloon catheter. 100 J was ultimately directly compared with RF effects on bronchial wall structures. Safety and efficacy of the ultrasound system was already previously established during renal denervation clinica stdies.

Results: 12 mongrel dogs were used. Bronchoscopy procedures were feasible in all cases, and no adverse effects were seen in any dogs. Lungs were collected for histology and H&E staining. With the optimized 100 J ultrasound energy we observed mild bronchial tissue injury, with minimal hemorrhage and preservation of respiratory epithelium. The RF catheter caused distinct focal injury points resulting from direct contact of the RF electrodes with bronchial wall tissue. Acute histological examination shows hemorrhagic injury along the RF energy path with significant necrosis to all bronchial wall elements including respiratory epithelium.

Conclusion: Ultrasound energy is safe, feasible, and at least as effective in affecting bronchoconstriction as RF energy offering a viable alternative to radiofrequency-based lung disease treatments.

Reporte de un caso

Squamous Cell Carcinoma of Lung with Skull Metastasis: A Case Report

Sanchayan Mandal, Devleena, Tamohan Chaudhuri and Subhra Sil

Background: Squamous cell carcinoma lung presents about 30 percent of all non small cell lung carcinoma. It almost always associated with smoking and usually spreads to brain, bones, liver, adrenal glands and small intestine. But, spreading to skull bones is a rare event.

Case Presentation: We here present a case of a 43 year old smoker with squamous cell carcinoma of lung where patient admitted with huge skull lesion invading through both inner and outer table and brain also. Previously, patient underwent lobectomy and three cycles of chemotherapy. This time, patient received palliative radiation to skull at our institute.

Conclusion: There is only single case report worldwide similar to this case and proved the unusual presentation of this rare occurrence. It also raises questions about the appropriate management of patients with intracranial metastasis with invasion of skull.

Artículo de investigación

Predictors of Functional Capacity in Patients with Pulmonary Hypertension

Rui Plácido, Susana Martins, João Silva Marques, Lara Kovell, Susana Gonçalves, Ana G. Almeida, António Nunes Diogo and Fausto Pinto

Introduction: The 6-minute walk test (6 MWT) distance is frequently used in the prediction of pulmonary hypertension (PH) prognosis. However, potential surrogates of this measure have not been established. We aim to describe the clinical, echocardiographic, and laboratorial criteria determining the 6 MWT distance in patients with PH.

Methods: In 22 consecutive PH patients, functional capacity was evaluated by the 6 MWT distance and compared with levels of neurohormonal activation biomarkers and echocardiographic parameters for right ventricular (RV) function.

Results: A correlation between the 6 MWT distance and several clinical parameters was found: Borg’s pre-test classification (R=-0.46; p=0.038); WHO functional class (p=0.029). Patients with higher levels of aldosterone (R=-0.46; p=0.030), renin (R=-0.43; p=0.046) and mid-regional pro-adrenomedullin (MR-proADM, R=-0.53; p=0.009) had worse 6 MWT performance. The opposite was true for natremia levels (R=0.55; p=0.006). There was a positive correlation between the 6 MWT distance and RV global longitudinal peak systolic strain rate and early diastolic strain rate (R=0.49; p=0.038 and R=-0.55; p=0.018, respectively). On multivariate analysis, only natremia and early diastolic strain rate were predictors of the 6 MWT distance.

Conclusion: The 6 MWT distance correlated with renin-angiotensin-aldosterone system activation and parameters for RV myocardial deformation. The new biomarker MR-proADM proved to be useful in the prediction of the functional capacity.

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