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2.
Blood ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978225

RESUMO

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase III REMARC study that randomized responding patients to RCHOP into maintenance lenalidomide or placebo. TMTV was computed on baseline PET/CT using the 41% SUVmax method; optimal TMTV cut-off for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301/650 evaluable patients (n=155 lenalidomide; n=146 placebo), including 192 patients classified as GCB/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3 (IQR: 78-523); optimal TMTV cut-off was 220 cm3. Patients with high TMTV >220 cm3 (vs low ≤220 cm3) showed worse/higher ECOG PS ≥2, stage III-IV disease, >1 extra-nodal sites, elevated LDH, IPI 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS (HR=2.3; P = .0002) and OS (HR=3.3; P = .0001), independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population.

3.
Int J Artif Organs ; : 391398819884941, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830841

RESUMO

BACKGROUND: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. METHODS: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute-right ventricular failure (N = 8, 11%) or chronic-right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an "all-subsets" approach. RESULTS: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular-free wall were the most significant predictors of acute-right ventricular failure (maximum receiver operating characteristic-area under the curve = 0.95, 95% confidence interval = 0.91-1.00, by the naïve Bayes), while the right ventricular-free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic-area under the curve = 0.97, 95% confidence interval = 0.91-1.00, according to naïve Bayes). CONCLUSION: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute-right ventricular failure and chronic-right ventricular failure, respectively.

5.
J Phys Chem A ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31386367

RESUMO

We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range allows us to study and disentangle shake processes and intramolecular inelastic scattering effects. In this gas-phase study, relative intensities of the carbon 1s photoelectron lines from chemically inequivalent carbon atoms in the same molecule have been measured as a function of the incident photon energy in the range of 300-6000 eV. We present relative cross sections for the chemically shifted carbon 1s lines in the photoelectron spectra of ethyl trifluoroacetate (the "ESCA" molecule). The results are compared with those of methyl trifluoroacetate and S-ethyl trifluorothioacetate as well as a series of chloro-substituted ethanes and 2-butyne. In the soft X-ray energy range, the cross sections show an extended X-ray absorption fine structure type of wiggles, as was previously observed for a series of chloroethanes. The oscillations are damped in the hard X-ray energy range, but deviations of cross-section ratios from stoichiometry persist, even at high energies. The current findings are supported by theoretical calculations based on a multiple scattering model. The use of soft and tender X-rays provides a more complete picture of the dominant processes accompanying photoionization. Such processes reduce the main photoelectron line intensities by 20-60%. Using both energy ranges enabled us to discern the process of intramolecular inelastic scattering of the outgoing electron, whose significance is otherwise difficult to assess for isolated molecules. This effect relates to the notion of the inelastic mean free path commonly used in photoemission studies of clusters and condensed matter.

6.
PLoS One ; 14(7): e0220490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365585

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure but classified into subgroups based on disease etiology. It is established that systemic bioenergetic dysfunction contributes to the pathogenesis of pulmonary arterial hypertension classified as World Health Organization (WHO) Group 1. Consistent with this, we previously showed that platelets from Group 1 PH patients demonstrate increased glycolysis and enhanced maximal capacity for oxidative phosphorylation, which is due to increased fatty acid oxidation (FAO). However, it remains unclear whether identical mitochondrial alterations contribute to the pathology of other PH subgroups. The most prevalent subgroup of PH is WHO Group 2, which encompasses pulmonary venous hypertension secondary to left heart disease. Here, we hypothesized that platelets from Group 2 subjects show bioenergetic alteration compared to controls, and that these changes were similar to Group 1 PH patients. METHOD AND RESULTS: We isolated platelets from subjects with Group 2 PH and controls (n = 20) and measured platelet bioenergetics as well as hemodynamic parameters. We demonstrate that Group 2 PH platelets do not show a change in glycolytic rate but do demonstrate enhanced maximal capacity of respiration due at least partially to increased FAO. Moreover, this enhanced maximal capacity correlates negatively with right ventricular stroke work index and is not changed by administration of inhaled nitrite, a modulator of pulmonary hemodynamics. CONCLUSIONS: These data demonstrate that Group 2 PH subjects have altered bioenergetic function though this alteration is not identical to that of Group 1 PH. The implications of this alteration for disease pathogenesis will be discussed.

7.
Int J Cardiovasc Imaging ; 35(12): 2157-2166, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31346831

RESUMO

2016 guidelines for the echographic evaluation of left ventricular filling pressure (LVFP) proposed a single algorithm with limited number of criteria (E/A ratio, tricuspid regurgitation velocity, left atrial volume index and average E/e') mainly related to left atrial pressure. Pulmonary venous flow analysis, evaluating more specifically left ventricular end diastolic pressure (LVEDP) has been withdrawn. We aim to evaluate the proportion of patients diagnosed with normal LVFP according to 2016 recommendations, despite an abnormal pulmonary venous flow profile suggesting high LVEDP. We prospectively studied patients with stable ischemic cardiomyopathy and aortic stenosis, before cardiac surgery. Extensive echocardiography was performed including pulmonary and mitral A wave durations. We included 76 patients (mean age 72 ± 10 years, 78% were men), 37 (49%) with aortic stenosis and 22 (29%) with ischemic cardiomyopathy. Mean left ventricular ejection fraction was 67 ± 11%. Applying recommendations, 58 patients had normal LVFP and 15 patients had high LVFP. Among the 58 patients with normal LVFP, 26 patients had Apd-Amd duration > 30 ms highly suggestive of high LVEDP. These patients had higher LV mass (112 ± 30 g/m2 vs. 86 ± 20 g/m2, p = 0.004) and shorter A wave duration (120 ± 13.6 ms vs. 132 ± 16.5 ms, p = 0.006) as compared to the remaining 15 patients with concordant evaluation (normal LVFP and normal Apd-Amd). In the present study, we found that 26/58 patients with low LVFP according to the 2016 recommendations had Apd-Amd suggestive of high LVEDP. Pulmonary venous flow should be added to the algorithm, particularly in patients with unexplained symptom, high LV mass or truncated mitral A wave.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia Doppler/normas , Fidelidade a Diretrizes/normas , Guias de Prática Clínica como Assunto/normas , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Pressão Ventricular , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/fisiopatologia , Cardiomiopatias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologia
8.
Annu Rev Biomed Eng ; 21: 33-60, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167107

RESUMO

Our review in the 2008 volume of this journal detailed the use of mechanical circulatory support (MCS) for treatment of heart failure (HF). MCS initially utilized bladder-based blood pumps generating pulsatile flow; these pulsatile flow pumps have been supplanted by rotary blood pumps, in which cardiac support is generated via the high-speed rotation of computationally designed blading. Different rotary pump designs have been evaluated for their safety, performance, and efficacy in clinical trials both in the United States and internationally. The reduced size of the rotary pump designs has prompted research and development toward the design of MCS suitable for infants and children. The past decade has witnessed efforts focused on tissue engineering-based therapies for the treatment of HF. This review explores the current state and future opportunities of cardiac support therapies within our larger understanding of the treatment options for HF.

9.
Phys Chem Chem Phys ; 21(25): 13600-13610, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31187832

RESUMO

In molecular photoemission, the analogue of the celebrated Young's double slit experiment is coherent electron emission from two equivalent atomic centers, giving rise to an interference pattern. Here multi-slit interference is investigated in inner-valence photoionization of propane, n-butane, isobutane and methyl peroxide. A more complex pattern is observed due to molecular orbital delocalization in polyatomic molecules, blurring the distinction between interference and diffraction. The potential to extract geometrical information is emphasized, as a more powerful extension of the EXAFS technique. Accurate reproduction of experimental features is obtained by simulations at the static Density Functional Theory level.

11.
Phys Chem Chem Phys ; 21(17): 8827-8836, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30972388

RESUMO

The Si 1s-1, Si 2s-1, and Si 2p-1 photoelectron spectra of the SiX4 molecules with X = F, Cl, Br, CH3 were measured. From these spectra the Si 1s-1 and Si 2s-1 lifetime broadenings were determined, revealing a significantly larger value for the Si 2s-1 core hole of SiF4 than for the same core hole of the other molecules of the sequence. This finding is in line with the results of the Si 2p-1 core holes of a number of SiX4 molecules, with an exceptionally large broadening for SiF4. For the Si 2s-1 core hole of SiF4 the difference to the other SiX4 molecules can be explained in terms of Interatomic Coulomb Decay (ICD)-like processes. For the Si 2p-1 core hole of SiF4 the estimated values for the sum of the Intraatomic Auger Electron Decay (IAED) and ICD-like processes are too small to explain the observed linewidth. However, the results of the given discussion render for SiF4 significant contributions from Electron Transfer Mediated Decay (ETMD)-like processes at least plausible. On the grounds of our results, some more molecular systems in which similar processes can be observed are identified.

12.
Phys Rev E ; 99(2-1): 022408, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30934335

RESUMO

Geometrical cues play an essential role in neuronal growth. Here, we quantify axonal growth on surfaces with controlled geometries and report a general stochastic approach that quantitatively describes the motion of growth cones. We show that axons display a strong directional alignment on micropatterned surfaces when the periodicity of the patterns matches the dimension of the growth cone. The growth cone dynamics on surfaces with uniform geometry is described by a linear Langevin equation with both deterministic and stochastic contributions. In contrast, axonal growth on surfaces with periodic patterns is characterized by a system of two generalized Langevin equations with both linear and quadratic velocity dependence and stochastic noise. We combine experimental data with theoretical analysis to measure the key parameters of the growth cone motion: angular distributions, correlation functions, diffusion coefficients, characteristics speeds, and damping coefficients. We demonstrate that axonal dynamics displays a crossover from an Ornstein-Uhlenbeck process to a nonlinear stochastic regime when the geometrical periodicity of the pattern approaches the linear dimension of the growth cone. Growth alignment is determined by surface geometry, which is fully quantified by the deterministic part of the Langevin equation. These results provide insight into the role of curvature sensing proteins and their interactions with geometrical cues.


Assuntos
Neurônios/citologia , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Proliferação de Células/efeitos dos fármacos , Dimetilpolisiloxanos/farmacologia , Modelos Neurológicos , Neurônios/efeitos dos fármacos , Nylons/farmacologia , Ratos
13.
Pulm Circ ; 9(2): 2045894019840646, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854934

RESUMO

Pulmonary hypertension (PH), a heterogeneous vascular disease, consists of subtypes with overlapping clinical phenotypes. MicroRNAs, small non-coding RNAs that negatively regulate gene expression, have emerged as regulators of PH pathogenesis. The muscle-specific micro RNA (miR)-204 is known to be depleted in diseased pulmonary artery smooth muscle cells (PASMCs), furthering proliferation and promoting PH. Alterations of circulating plasma miR-204 across the trans-pulmonary vascular bed might provide mechanistic insights into the observed intracellular depletion and may help distinguish PH subtypes. MiR-204 levels were quantified at sequential pulmonary vasculature sites in 91 patients with World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) (n = 47), Group II PH (n = 22), or no PH (n = 22). Blood from the right atrium/superior vena cava, pulmonary artery, and pulmonary capillary wedge was collected. Peripheral blood mononuclear cells (PBMCs) were isolated (n = 5/group). Excretion of miR-204 by PAH-PASMCs was also quantified in vitro. In Group I patients only, miR-204 concentration increased sequentially along the pulmonary vasculature (log fold-change slope = 0.22 [95% CI = 0.06-0.37], P = 0.008). PBMCs revealed insignificant miR-204 variations among PH groups ( P = 0.12). Cultured PAH-PAMSCs displayed a decrease of intracellular miR-204 ( P = 0.0004), and a converse increase of extracellular miR-204 ( P = 0.0018) versus control. The stepwise elevation of circulating miR-204 across the pulmonary vasculature in Group I, but not Group II, PH indicates differences in muscle-specific pathobiology between subtypes. Considering the known importance of miR-204 in PH, these findings may suggest pathologic excretion of miR-204 in Group I PAH by PASMCs, thereby accounting for decreased intracellular miR-204 concentration.

14.
Proc Natl Acad Sci U S A ; 116(11): 4877-4882, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30733297

RESUMO

Observing and controlling molecular motion and in particular rotation are fundamental topics in physics and chemistry. To initiate ultrafast rotation, one needs a way to transfer a large angular momentum to the molecule. As a showcase, this was performed by hard X-ray C1s ionization of carbon monoxide accompanied by spinning up the molecule via the recoil "kick" of the emitted fast photoelectron. To visualize this molecular motion, we use the dynamical rotational Doppler effect and an X-ray "pump-probe" device offered by nature itself: the recoil-induced ultrafast rotation is probed by subsequent Auger electron emission. The time information in our experiment originates from the natural delay between the C1s photoionization initiating the rotation and the ejection of the Auger electron. From a more general point of view, time-resolved measurements can be performed in two ways: either to vary the "delay" time as in conventional time-resolved pump-probe spectroscopy and use the dynamics given by the system, or to keep constant delay time and manipulate the dynamics. Since in our experiment we cannot change the delay time given by the core-hole lifetime τ, we use the second option and control the rotational speed by changing the kinetic energy of the photoelectron. The recoil-induced rotational dynamics controlled in such a way is observed as a photon energy-dependent asymmetry of the Auger line shape, in full agreement with theory. This asymmetry is explained by a significant change of the molecular orientation during the core-hole lifetime, which is comparable with the rotational period.

15.
Phys Chem Chem Phys ; 21(10): 5448-5454, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30793147

RESUMO

Hard X-ray electron spectroscopic study of iodine 1s and 2s photoionization of iodomethane (CH3I) and trifluoroiodomethane (CF3I) molecules is presented. The experiment was carried out at the SPring-8 synchrotron radiation facility in Japan. The results are analyzed with the aid of relativistic molecular and atomic calculations. It is shown that charge redistribution within the molecule is experimentally observable even for very deep levels and is a function of the number of electron vacancies. We also show that the analysis of Auger spectra subsequent to hard X-ray photoionization can be used to provide insight into charge distribution in molecules and highlight the necessity of quantum electrodynamics corrections in the prediction of core shell binding energies in molecules that contain heavy atoms.

16.
Heart ; 105(2): 117-121, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30093545

RESUMO

OBJECTIVES: To evaluate the prognostic value of the ratio between tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) as a determinant of right ventricular to pulmonary artery (RV-PA) coupling in patients undergoing transcatheter aortic valve replacement (TAVI). BACKGROUND: RV function and pulmonary hypertension (PH) are both prognostically important in patients receiving TAVI. RV-PA coupling has been shown to be prognostic important in patients with heart failure but not previously evaluated in TAVI patients. METHODS: Consecutive patients with severe aortic stenosis who received TAVI from July 2011 through January 2016 and with comprehensive baseline echocardiogram were included. All individual echocardiographic images and Doppler data were independently reviewed and blinded to the clinical information and outcomes. Cox models quantified the effect of TAPSE/PASP quartiles on subsequent all-cause mortality while adjusting for confounders. RESULTS: A total of 457 patients were included with mean age of 82.8±7.2 years, left ventricular ejection fraction (LVEF) 54%±13%, PASP 44±17 mm Hg. TAPSE/PASP quartiles showed a dose-response relationship with survival. This remained significant (HR for lowest quartile vs highest quartile=2.21, 95% CI 1.07 to 4.57, p=0.03) after adjusting for age, atrial fibrillation, LVEF, stroke volume index, Society of Thoracic Surgeons Predicted Risk of Mortality. CONCLUSION: Baseline TAPSE/PASP ratio is associated with all-cause mortality in TAVI patients as it evaluates RV systolic performance at a given degree of afterload. Incorporation of right-side unit into the risk stratification may improve optimal selection of patients for TAVI.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ventrículos do Coração/cirurgia , Artéria Pulmonar/cirurgia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Ecocardiografia Doppler , Feminino , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Função Ventricular Esquerda , Função Ventricular Direita
17.
Trends Cardiovasc Med ; 29(4): 207-217, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30177249

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is defined as clinical features of heart failure, ideally with biomarker evidence such as elevated plasma natriuretic peptide levels, in the setting of an ejection fraction (EF) greater than 50% and imaging evidence of diastolic left ventricular dysfunction [1,2]. In the absence of cardiac imaging or invasive hemodynamics, this is a clinical syndrome that is often indistinguishable from heart failure with reduced ejection fraction (HFrEF). HFpEF and HFrEF present with a cadre of comparable signs and symptoms including jugular venous distention, pulmonary rales on auscultation, breathlessness, orthopnea, exercise intolerance, exertional dyspnea, fatigue and peripheral edema. HFpEF accounts for at least half of all diagnoses of heart failure [1,2]. Pulmonary hypertension (PH) is a common complication of HFpEF that is linked to worse disease morbidity and mortality. In fact, mortality has been linked to increases in the intrinsic pulmonary vascular resistance in the setting of increased left ventricular end diastolic pressure, characterized hemodynamically by rises in the transpulmonary pressure gradient, pulmonary vascular resistance or diastolic pressure gradient. Despite being the most common form of PH, there are no approved therapies for the treatment of PH secondary to HFpEF. This review will summarize the hemodynamic classifications of PH in the setting of HFpEF, mechanisms of disease, the potential contribution of pulmonary vascular disease to poor outcomes in patients with HFpEF, and new approaches to therapy.


Assuntos
Pressão Arterial , Insuficiência Cardíaca/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Animais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/terapia , Prognóstico , Circulação Pulmonar , Fatores de Risco , Remodelação Vascular , Resistência Vascular
18.
J Chem Phys ; 149(20): 204313, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30501230

RESUMO

The photodissociation dynamics of CH3I and CH2ClI at 272 nm were investigated by time-resolved Coulomb explosion imaging, with an intense non-resonant 815 nm probe pulse. Fragment ion momenta over a wide m/z range were recorded simultaneously by coupling a velocity map imaging spectrometer with a pixel imaging mass spectrometry camera. For both molecules, delay-dependent pump-probe features were assigned to ultraviolet-induced carbon-iodine bond cleavage followed by Coulomb explosion. Multi-mass imaging also allowed the sequential cleavage of both carbon-halogen bonds in CH2ClI to be investigated. Furthermore, delay-dependent relative fragment momenta of a pair of ions were directly determined using recoil-frame covariance analysis. These results are complementary to conventional velocity map imaging experiments and demonstrate the application of time-resolved Coulomb explosion imaging to photoinduced real-time molecular motion.

19.
Rev Sci Instrum ; 89(11): 113101, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30501280

RESUMO

The detection efficiency η of any particle detector is important, concerning acquisition time, but becomes even more critical when two particles are detected in coincidence, with a total efficiency η1η2, in order to allow a deeper understanding of complex processes induced by light or particle interaction with matter. Efficiency and resolution of a time and position sensitive x-ray detector are reported here. This system consists of a multilayer transmission photocathode and two micro-channel plates (MCPs) equipped with a delay line anode (DLA). The efficiency is found to be about 20% for Al Kα photons, while the spatial resolution is comparable to that of a standard DLA detector (about 100 µm). The fast response time of the detector combined with its efficiency should allow coincidence experiments between x-ray photons and other particles (electron, ions, etc.).

20.
Comp Med ; 68(6): 461-473, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30541636

RESUMO

Pulmonary arterial hypertension (PAH) is a life-threatening disease with higher incidence in HIV-infected compared with noninfected patients. SIV-infected NHP develop clinical manifestations of HIV infection, including PAH. To understand the pathogenesis of PAH and determine the relationship between hemodynamic changes and clinical characteristics associated with SIV infection, we performed right heart catheterization and echocardiographic imaging of 21 rhesus macaques before and after SIV infection. Between 6 and 12 mo after infection, 11 of the 21 animals had elevated mean pulmonary arterial pressure (mPAP; greater than 25 mm Hg). RV involvement was evident as increased RV glucose uptake in PAH+ macaques on positron emission tomography-coupled CT compared with uninfected animals. RV and pulmonary vascular collagen deposition were elevated in PAH+ animals. At 12 mo after infection, 6 of the 21 macaques (28.6%) exhibited continued increase in mPAP (progressive PAH), whereas 5 animals (23.8%) had reduced pressure (transient PAH). SIV infection of rhesus macaques led to 3 distinct outcomes with regard to hemodynamic function. Hemodynamic alterations correlated with specific inflammatory profiles and increased RV and pulmonary arterial fibrosis but not with viral load, sex, or CD4+ T-cell levels. This model of a natural cause of PAH provides insight into disease pathways that are important for the development of novel therapeutic targets.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Vírus da Imunodeficiência Símia , Animais , Contagem de Linfócito CD4 , Modelos Animais de Doenças , Ecocardiografia , Feminino , Glucose/metabolismo , Infecções por HIV/complicações , Hemodinâmica , Macaca mulatta , Masculino , Artéria Pulmonar/patologia , Carga Viral
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