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1.
Vascul Pharmacol ; 122-123: 106599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31629919

RESUMO

Targeting vascular remodeling in pulmonary arterial hypertension (PAH) remains a challenge given the lack of potent anti-remodeling abilities of the therapeutic drugs. Although sildenafil has been shown to ameliorate cardiopulmonary remodeling, that of tadalafil is questionable. Masitinib, a tyrosine kinase inhibitor appears safer and more potent than imatinib for treatment of malignancies, but its efficacy on PAH is unknown. Therefore, we investigated the anti-remodeling properties of masitinib (5, 15, 50 mg/kg) and tadalafil (5, 10 mg/kg) using a monocrotaline-induced rat model of PAH. The 14-day treatment with masitinib (15, 50 mg/kg) resulted in significantly decreased right ventricular (RV) systolic pressure (RVSP) and hypertrophy (RVH), and pulmonary vascular remodeling, whereas tadalafil showed weaker anti-remodeling properties. Besides, masitinib significantly blocked the mitogen-associated protein kinase (MAPK) pathway, and reduced phosphodiesterase (PDE)-5 mRNA expression in the lungs. By contrast, tadalafil did not significantly inhibit the MAPK pathway. Further, the 28-day treatment extension revealed that masitinib-treated rats (15 mg/kg) had significantly lower RVSP, and higher heart rate and serum cyclic guanosine monophosphate (cGMP) level, whereas those treated with tadalafil (10 mg/kg) showed insignificantly lower RVSP and higher cGMP level. Moreover, the RVH indices, heart rates, body weight gains, and survival rates of rats in both groups were comparable. Collectively, these results suggest that the treatment with a low-dose masitinib was non-inferior than tadalafil. A lower dose of masitinib may represent a novel approach to target both the cardiopulmonary remodeling and the dysregulated vasoconstriction in PAH.


Assuntos
Anti-Hipertensivos/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Tadalafila/farmacologia , Tiazóis/farmacologia , Remodelação Vascular/efeitos dos fármacos , Animais , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Terapia de Alvo Molecular , Monocrotalina , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Transdução de Sinais , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
2.
Pediatr Cardiol ; 40(8): 1756-1758, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31367951

RESUMO

The evaluation of oncologic patients at risk of chemotherapy-induced cardiotoxicity usually focuses on left ventricular function. However, recent studies have demonstrated that right ventricle impairment often coexists (and in some cases precedes) left-side affectation. We present the case of a 19-year-old heart transplant recipient who developed severe right ventricular dysfunction secondary to treatment of an abdominal lymphoma.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Linfoma de Células B/tratamento farmacológico , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita/efeitos dos fármacos , Cardiotoxicidade/etiologia , Ecocardiografia , Feminino , Transplante de Coração/efeitos adversos , Humanos , Transplantados , Disfunção Ventricular Direita/fisiopatologia , Adulto Jovem
3.
Methodist Debakey Cardiovasc J ; 15(2): 138-144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384377

RESUMO

Ebstein's anomaly is a malformation of the tricuspid valve with myopathy of the right ventricle (RV) that presents with variable anatomic and pathophysiologic characteristics, leading to equally variable clinical scenarios. Medical management and observation is often recommended for asymptomatic patients and may be successful for many years. Tricuspid valve repair is the goal of operative intervention; repair also typically includes RV plication, right atrial reduction, and atrial septal closure or subtotal closure. Postoperative functional assessments generally demonstrate an improvement or relative stability related to degree of RV enlargement, RV dysfunction, RV fractional area change, and tricuspid valve regurgitation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Fármacos Cardiovasculares/uso terapêutico , Anomalia de Ebstein/terapia , Insuficiência da Valva Tricúspide/terapia , Valva Tricúspide/efeitos dos fármacos , Valva Tricúspide/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Anomalia de Ebstein/complicações , Anomalia de Ebstein/diagnóstico por imagem , Anomalia de Ebstein/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento , Valva Tricúspide/anormalidades , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/tratamento farmacológico , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/fisiopatologia , Função Ventricular Direita/efeitos dos fármacos
4.
J Vasc Res ; 56(4): 204-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189158

RESUMO

The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O2-sensitive KV channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O2-sensitive KV channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.


Assuntos
Anti-Hipertensivos/farmacologia , Epoprostenol/análogos & derivados , Hipóxia/complicações , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Hipertensão Arterial Pulmonar/tratamento farmacológico , Receptores de Prostaglandina E Subtipo EP4/agonistas , Vasodilatadores/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Epoprostenol/farmacologia , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Oxigênio/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais , Regulação para Cima , Remodelação Vascular/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos
5.
Circ Res ; 124(11): 1551-1567, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31120820

RESUMO

The past 2 decades have witnessed a >40% improvement in mortality for patients with heart failure and left ventricular systolic dysfunction. 1 This success has coincided with the stepwise availability of drugs that target neurohormonal activation: ß-adrenergic receptor blockers (ß-blockers), ACE (angiotensin-converting enzyme) inhibitors and ANG (angiotensin) II blockers, neprilysin inhibitors, and aldosterone antagonists. Our understanding of right heart failure (RHF) has lagged behind and many proven targeted therapies for left heart failure do not appear to provide similar benefits for RHF. Until recently, the right ventricle (RV) has often been viewed as less important than the left ventricle and in contemporary literature received the moniker "The Forgotten Ventricle". Recent advances in echocardiography and magnetic resonance imaging have enabled detailed assessments of RV anatomy and physiology in both health and disease allowing us to more accurately describe the clinical sequelae and end-organ manifestations of RHF. RV function is now recognized as one of the most important predictors of prognosis in many cardiovascular disease states. 2 Despite the significance of RV function to survival, there are no clinically approved therapies that directly nor selectively improve RV function. As well, relative to our understanding of left heart failure, the basis for RHF remains poorly understood. This article aims to condense the current knowledge on RV adaptation and failure, review current management strategies for RHF, and explore evolving therapeutic approaches.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Disfunção Ventricular Direita/tratamento farmacológico , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Fármacos Cardiovasculares/efeitos adversos , Progressão da Doença , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Fatores de Risco , Transplante de Células-Tronco , Resultado do Tratamento , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/mortalidade , Disfunção Ventricular Direita/fisiopatologia
6.
J Vasc Res ; 56(3): 117-128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31085922

RESUMO

Previous studies have shown that metformin (MET) prevents experimental pulmonary arterial hypertension (PAH) and that activation of autophagy is involved in the development of pulmonary vascular remodeling. However, the mechanism of how MET inhibits autophagy and reverses pulmonary vascular remodeling is still unclear. The objective of the present study was to investigate the role of autophagy in MET-induced hypoxia PAH protection and the underlying mechanisms. To examine the effects of MET on hypoxia, we treated rats with MET (100 mg/kg/day) after 3 weeks of hypoxia. Hemodynamic changes, weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio, and lung morphological features were examined after 3 weeks. In addition, alpha smooth muscle actin (α-SMA), p62, and PCNA were assessed by immunofluorescence and immunohistochemistry staining. BECN-1, LC3B, p62, and activation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed by Western blotting. Cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) and the 5-ethynyl-2'-deoxyuridine staining kit assay. Hypoxia induced increases in right ventricular systolic pressure and the RV/LV+S ratio, which were attenuated by MET treatment. MET also inhibited hypoxia-induced pulmonary vascular remodeling, collagen deposition, proliferation of pulmonary arterial smooth muscle cells, elevation of BECN-1 and the LC3B-II/-I ratio, and downregulation of p62. Further studies found that this process was mediated by inhibition of autophagy and activation of the AMPK signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Metformina/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática , Humanos , Hipóxia/complicações , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Hipertensão Arterial Pulmonar/enzimologia , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/enzimologia , Artéria Pulmonar/patologia , Ratos Wistar , Transdução de Sinais , Remodelação Vascular/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
7.
PLoS One ; 14(4): e0214740, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964911

RESUMO

Pulmonary hypertension (PH) increases the work of the right ventricle (RV) and causes right-sided heart failure. This study examined RV mitochondrial function and ADP transfer in PH animals advancing to right heart failure, and investigated a potential therapy with the specific ß1-adrenergic-blocker metoprolol. Adult Wistar rats (317 ± 4 g) were injected either with monocrotaline (MCT, 60 mg kg-1) to induce PH, or with an equivalent volume of saline for controls (CON). At three weeks post-injection the MCT rats began oral metoprolol (10 mg kg-1 day-1-) or placebo treatment until heart failure was observed in the MCT group. Mitochondrial function was then measured using high-resolution respirometry from permeabilised RV fibres. Relative to controls, MCT animals had impaired mitochondrial function but maintained coupling between myofibrillar ATPases and mitochondria, despite an increase in ADP diffusion distances. Cardiomyocytes from the RV of MCT rats were enlarged, primarily due to an increase in myofibrillar protein. The ratio of mitochondria per myofilament area was decreased in both MCT groups (p ≤ 0.05) in comparison to control (CON: 1.03 ± 0.04; MCT: 0.74 ± 0.04; MCT + BB: 0.74 ± 0.03). This not only implicates impaired energy production in PH, but also increases the diffusion distance for metabolites within the MCT cardiomyocytes, adding an additional hindrance to energy supply. Together, these changes may limit energy supply in MCT rat hearts, particularly at high cardiac workloads. Metoprolol treatment did not delay the onset of heart failure symptoms, improve mitochondrial function, or regress RV hypertrophy.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Metoprolol/farmacologia , Mitocôndrias/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Administração Oral , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Animais , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Metoprolol/uso terapêutico , Mitocôndrias/metabolismo , Monocrotalina/toxicidade , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miofibrilas/metabolismo , Miofibrilas/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Efeito Placebo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Cardiovasc Imaging ; 35(6): 1009-1017, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941563

RESUMO

Right ventricular (RV) impairment after cancer therapy-related cardiotoxicity and its prognostic implications in lung cancer have not been examined. The present research sought to evaluate RV structure, function, and mechanics in stage III non-small-cell lung cancer (NSCLC) before and after concurrent chemoradiotherapy (CCRT), and to explore the associations between RV impairments, radiation dose, and all-cause mortality. This prospective investigation included 128 inoperable NSCLC patients who were scheduled to receive CCRT. Echocardiographic examination and strain evaluation was performed at baseline and 6 months post-CCRT in all participants. Conventional RV dimensions revealed no significant changes post-CCRT. However, a reduction in RV free wall strain (RV-fwLS) was observed at 6 months post-CCRT (- 28.3 ± 4.6% vs. - 25.5 ± 4.8%, P < 0.001). The same was revealed for global RV longitudinal strain (RV-GLS) (- 23.4 ± 2.9% vs. - 20.2 ± 3.4%, P < 0.001). Pearson correlation showed that RV radiation mean dose was related with the percentage change in RV-fwLS (r = 0.303, P = 0.001) and RV-GLS (r = 0.284, P = 0.002). In multivariable analysis, the percentage change in RV-fwLS was an independent predictor of all-cause mortality (HR 1.296, 95% CI 1.202-1.428, P < 0.001). RV longitudinal strain is deteriorated at 6 months post-CCRT. The RV mechanics deterioration was associated with radiation dose and affected the long-term outcome of stage III NSCLC patients treated with CCRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Contração Miocárdica/efeitos da radiação , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita/efeitos da radiação , Adolescente , Adulto , Idoso , Fenômenos Biomecânicos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cardiotoxicidade , Quimiorradioterapia/mortalidade , Ecocardiografia Doppler , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Estadiamento de Neoplasias , Estudos Prospectivos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita/efeitos dos fármacos , Adulto Jovem
9.
J Cardiovasc Pharmacol ; 73(3): 178-185, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30839511

RESUMO

INTRODUCTION: Hepatopulmonary syndrome and portopulmonary hypertension are common complications of liver disorders. This study aimed to determine roles of ET-B receptors and endothelial-derived NO synthase in the regulation of pulmonary hemodynamic in cirrhotic rats. METHODS: Male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 28 days, animals were anesthetized, and the right ventricle, femoral artery, and vein cannulated. Then, intravenous injection of BQ-788 (a selective ET-B receptor antagonist) and L-NAME (eNOS inhibitor) were performed sequentially. RESULTS: After the first injection of BQ-788, the right ventricular systolic pressure (RVSP) and mean arterial systemic pressure increased only in the Sham group. L-NAME increased RVSP in the Sham and CBDL groups, whereas mean arterial systemic pressure elevated only in the Sham group significantly. Reinjection of BQ-788 increased RVSP in the Sham group, whereas it decreased RVSP in the CBDL group. Both plasma NO metabolites and lung endothelin-1 increased in the CBDL group. CONCLUSION: ET-B receptors on the endothelial cells play roles in the regulation of pulmonary and systemic vascular tone in normal condition through the NO-mediated pathway, whereas ET-B receptors on the smooth muscle cells have a role in the pulmonary vascular tone in liver cirrhosis.


Assuntos
Hemodinâmica , Síndrome Hepatopulmonar/enzimologia , Cirrose Hepática Experimental/enzimologia , Óxido Nítrico Sintase Tipo III/metabolismo , Artéria Pulmonar/enzimologia , Circulação Pulmonar , Receptor de Endotelina B/metabolismo , Animais , Pressão Arterial/efeitos dos fármacos , Células Endoteliais/enzimologia , Endotelina-1/metabolismo , Síndrome Hepatopulmonar/fisiopatologia , Cirrose Hepática Experimental/fisiopatologia , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Função Ventricular Direita/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
10.
Am J Physiol Regul Integr Comp Physiol ; 316(6): R716-R724, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840485

RESUMO

The glucocorticosteroid betamethasone is routinely administered via maternal intramuscular injection to enhance fetal lung maturation before anticipated preterm birth. Although antenatal betamethasone increases fetal pulmonary arterial (PA) blood flow, whether this agent alters the contribution of 1) right ventricular (RV) output or 2) left-to-right shunting across the ductus arteriosus to rises in PA blood flow after preterm birth is unknown. To address this question, anesthetized control (n = 7) and betamethasone-treated (n = 7) preterm fetal lambs (gestation 127 ± 1 days, means ± SD) were instrumented with aortic, pulmonary, and left atrial catheters as well as ductus arteriosus and left PA flow probes to calculate RV output, with hemodynamics measured for 30 min after cord clamping and mechanical ventilation. Mean PA blood flow was higher in betamethasone-treated than in control lambs over the initial 10 min after birth (P < 0.05). This higher PA flow was accompanied by 1) a greater pulmonary vascular conductance (P ≤ 0.025), 2) a larger proportion of RV output passing to lungs (P ≤ 0.01), despite a fall in this output, and 3) earlier reversal and a greater magnitude (P ≤ 0.025) of net ductal shunting, due to the combination of higher left-to-right (P ≤ 0.025) and lesser right-to-left phasic shunting (P ≤ 0.025). These results suggest that antenatal betamethasone augments the initial rise in PA blood flow after birth in preterm lambs, with this augmented rise supported by the combination of 1) a greater redistribution of RV output toward the lungs and 2) a faster and larger reversal in net ductal shunting underpinned not only by greater left-to-right, but also by lesser right-to-left phasic shunting.


Assuntos
Betametasona/administração & dosagem , Canal Arterial/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Pulmão/irrigação sanguínea , Nascimento Prematuro , Circulação Pulmonar/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Esquema de Medicação , Canal Arterial/fisiopatologia , Feminino , Idade Gestacional , Gravidez , Carneiro Doméstico , Fatores de Tempo
11.
Life Sci ; 219: 82-89, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30605649

RESUMO

AIM: Pulmonary hypertension due to left heart failure (PH-LHF) is the most common cause of pulmonary hypertension. However, therapies for PH-LHF are lacking. Therefore, we investigated the effects and potential mechanism of dehydroepiandrosterone (DHEA) treatment in an experimental model of PH-LHF. MAIN METHOD: PH-LHF was induced in rats via ascending aortic banding. The rats then received daily DHEA from Day 1 to Day 63 for the prevention protocol or from Day 49 to Day 63 for the reversal protocol. Other ascending aortic banding rats were left untreated to allow development of PH and right ventricular (RV) failure. Sham ascending aortic banding rats served as controls. KEY FINDING: Significant increases in mean pulmonary arterial pressure (mPAP) and right ventricular end-diastolic diameter (RVEDD) were observed in the PH-LHF group. Therapy with DHEA prevented LHF-induced PH and RV failure by preserving mPAP and preventing RV hypertrophy and pulmonary artery remodeling. In preexisting severe PH, DHEA attenuated most lung and RV abnormalities. The beneficial effects of DHEA in PH-LHF seem to result from depression of the STAT3 signaling pathway in the lung. SIGNIFICANT: DHEA not only prevents the development of PH-LHF and RV failure but also rescues severe preexisting PH-LHF.


Assuntos
Desidroepiandrosterona/uso terapêutico , Insuficiência Cardíaca/complicações , Hipertensão Pulmonar/etiologia , Artéria Pulmonar/fisiopatologia , Remodelação Vascular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Animais , Western Blotting , Modelos Animais de Doenças , Ecocardiografia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Masculino , Artéria Pulmonar/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
12.
Cardiovasc Drugs Ther ; 33(1): 87-95, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30675708

RESUMO

The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF < 50%, and New York Heart Association functional class II to IV symptoms will be randomized to empagliflozin 10 mg for 6 months or placebo. All patients will undergo cardiac magnetic resonance (CMR), cardiopulmonary exercise test (CPET), 6-min walk test, and quality of life questionnaires. The primary outcome is the change in left ventricular end-diastolic volume measured by CMR. Secondary end-points include change in peak VO2 (CPET); change in LV mass, in LVEF, in myocardial mechanics (strains), in left atrium volumes, in RV function and volumes, in interstitial myocardial fibrosis, and in epicardial adipose tissue (CMR); change in the distance in the 6-min walk test; and changes in quality of life (Kansas Cardiomyopathy questionnaire [KCCQ-12] and the 36-Item Short Form Survey [SF-36]). Safety issues (e.g., hypoglycemia, urinary infections, ketoacidosis,…) will also be monitored. In summary, EMPA-TROPISM clinical trial will determine whether the SGLT2 inhibitor empagliflozin improves cardiac function and heart failure parameters in non-diabetic HF patients (EMPA-TROPISM [ATRU-4]: Are the "cardiac benefits" of Empagliflozin independent of its hypoglycemic activity; NCT 03485222).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Cidade de Nova Iorque , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Teste de Caminhada
13.
Int J Cardiovasc Imaging ; 35(3): 441-450, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30350115

RESUMO

Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17ß-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLSFW) and RV longitudinal shortening fraction (RVLSF) were also used to quantify RV function. RV morphology was determined by echocardiographic and histological analysis. TAPSE, RVFAC and s' were reduced, and RIMP was elevated in the MCT-treated group and vehicle-treated group, when compared with control group (P < 0.01). TAPSE, RVFAC and s' in the E2 group were higher, while RIMP was lower than those in the MCT-treated group and vehicle-treated group (P < 0.01). Myocardial functional parameters (RVLSFW and RVLSF) were also higher in the E2 group. Enhanced serum E2 levels were closely correlated with the improvement in RV functional parameters and enhancement of serum BNP levels (P < 0.01 for all groups). RV function decreased significantly in male rats with MCT-induced PAH, while E2 exhibited a protective effect on RV function, suggesting that E2 is a critical modulator of sex differences in PAH.


Assuntos
Ecocardiografia , Estradiol/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertrofia Ventricular Direita/prevenção & controle , Disfunção Ventricular Direita/prevenção & controle , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Estradiol/sangue , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/sangue , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertrofia Ventricular Direita/fisiopatologia , Masculino , Monocrotalina , Peptídeo Natriurético Encefálico/sangue , Ratos Sprague-Dawley , Fatores de Tempo , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologia
14.
Cardiovasc Toxicol ; 19(3): 220-228, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30242562

RESUMO

It was aimed to investigate possible late cardiac effects of Sulfur mustard (SM) exposure in Iranian veterans. Thirty-eight veterans with late complications of SM exposure were investigated. Clinical history, physical examinations, 12 leads electrocardiography and transthoracic echocardiography were performed. Computed tomography coronary angiography (CTCA) was performed as clinically indicated for angiographic assessment and patients were stratified according to the CTCA findings. Incomplete right bundle branch block and right axis deviation were detected in 3 (7.9%) and 4 (10.5%) cases, respectively. Mean value of left ventricular ejection fraction was 55.7 ± 2.9%. Different degrees of right ventricular dilation was observed in seven (18.4%) patients. All the patients showed mild to moderate degrees of tricuspid regurgitation. Increased pulmonary artery pressure (PAP) was detected in 16 (42.1%) patients. Out of 18 patients who underwent CTCA, non-obstructive and obstructive coronary artery disease (CAD) were observed in three (16.66%) and eight (44.44%) patients, respectively. CAD was stratified to single vessel (5.5%), two vessels (27.8%) and three vessels disease (11.1%). Mean coronary artery calcium score was 50.91 ± 115.58. SM has cardiovascular toxicity, as a delayed complication of this chemical warfare poisoning.


Assuntos
Substâncias para a Guerra Química/envenenamento , Cardiopatias/induzido quimicamente , Gás de Mostarda/envenenamento , Exposição Ocupacional/efeitos adversos , Saúde dos Veteranos , Adulto , Idoso , Bloqueio de Ramo/induzido quimicamente , Cardiotoxicidade , Doença da Artéria Coronariana/induzido quimicamente , Estudos Transversais , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Tempo , Insuficiência da Valva Tricúspide/induzido quimicamente , Calcificação Vascular/induzido quimicamente , Disfunção Ventricular Esquerda/induzido quimicamente , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
15.
Int J Cardiol ; 274: 245-247, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30193794

RESUMO

BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics. METHODS AND RESULTS: We searched electronic medical records from 2 institutions over 4 years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus 1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n = 112) were RAP, median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean ±â€¯standard deviation = 1.8 ±â€¯0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use. CONCLUSION: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Função Ventricular Direita/fisiologia , Benzazepinas/uso terapêutico , Creatinina/sangue , Diurese/efeitos dos fármacos , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Tolvaptan/uso terapêutico , Resultado do Tratamento , Função Ventricular Direita/efeitos dos fármacos
16.
Cardiovasc Res ; 115(2): 432-439, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30032282

RESUMO

Aims: Pulmonary arterial hypertension (PAH) is associated with increased levels of circulating growth factors and corresponding receptors such as platelet derived growth factor, fibroblast growth factor and vascular endothelial growth factor. Nintedanib, a tyrosine kinase inhibitor targeting primarily these receptors, is approved for the treatment of patients with idiopathic pulmonary fibrosis. Our objective was to examine the effect of nintedanib on proliferation of human pulmonary microvascular endothelial cells (MVEC) and assess its effects in rats with advanced experimental pulmonary hypertension (PH). Methods and results: Proliferation was assessed in control and PAH MVEC exposed to nintedanib. PH was induced in rats by subcutaneous injection of Sugen (SU5416) and subsequent exposure to 10% hypoxia for 4 weeks (SuHx model). Four weeks after re-exposure to normoxia, nintedanib was administered once daily for 3 weeks. Effects of the treatment were assessed with echocardiography, right heart catheterization, and histological analysis of the heart and lungs. Changes in extracellular matrix production was assessed in human cardiac fibroblasts stimulated with nintedanib. Decreased proliferation with nintedanib was observed in control MVEC, but not in PAH patient derived MVEC. Nintedanib treatment did not affect right ventricular (RV) systolic pressure or total pulmonary resistance index in SuHx rats and had no effects on pulmonary vascular remodelling. However, despite unaltered pressure overload, the right ventricle showed less dilatation and decreased fibrosis, hypertrophy, and collagen type III with nintedanib treatment. This could be explained by less fibronectin production by cardiac fibroblasts exposed to nintedanib. Conclusion: Nintedanib inhibits proliferation of pulmonary MVECs from controls, but not from PAH patients. While in rats with experimental PH nintedanib has no effects on the pulmonary vascular pathology, it has favourable effects on RV remodelling.


Assuntos
Indóis/farmacologia , Miocárdio/patologia , Inibidores de Proteínas Quinases/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Humanos , Masculino , Miocárdio/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Pirróis , Ratos Sprague-Dawley , Adulto Jovem
17.
Clin Rheumatol ; 38(1): 29-35, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29362961

RESUMO

Urotensin II (UII) has been reported to play a key role in pulmonary arterial hypertension (PAH) development. Doppler echocardiography, a noninvasive and simple tool, is recommended for diagnosing PAH. This study was designed to investigate the effect of urantide, a UII receptor antagonist, on the structure and function of the right ventricle in PAH rat models by Doppler echocardiography. A total of 60 male rats were divided into two groups: early- and late-treatment groups. Rats in the urantide and MCT (monocrotaline) subgroups were injected with 10 µg/kg urantide in the urantide group or an equal amount of normal saline in the MCT group 1 week after PAH model construction in the early-treatment group and 4 weeks after the construction in the late-treatment group. Rats in the control group received an equal volume of normal saline solution. PAH-related indexes were measured by echocardiography. PAH rat models exhibited higher right ventricular diastolic diameter and lower time to peak, ejection time, and peak flow velocity of pulmonary artery than controls (P < 0.05). However, compared with the MCT group, all abovementioned indexes were improved in the urantide group (P < 0.05). No significant differences in pulmonary artery diameter and left ventricular ejection fraction were noted among the groups. Compared with the MCT group, systolic pulmonary arterial pressure (SPAP) and mean pulmonary arterial pressure (mPAP) were significantly lower in the urantide group (P < 0.05). SPAP examined by echocardiography was correlated with mPAP by catheterization (P < 0.05). Urantide treatment improved right heart failure parameters in MCT-induced PAH rats, thus providing a potential new strategy for treating PAH.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Urotensinas/farmacologia , Função Ventricular Direita/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ecocardiografia Doppler , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/diagnóstico por imagem , Masculino , Monocrotalina , Artéria Pulmonar/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
Am J Respir Crit Care Med ; 199(12): 1550-1560, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30557518

RESUMO

Rationale: Remodeling and fibrosis of the right ventricle (RV) may cause RV dysfunction and poor survival in patients with pulmonary hypertension. Objectives: To investigate the consequences of RV fibrosis modulation and the accompanying cellular changes on RV function. Methods: Expression of fibrotic markers was assessed in the RV of patients with pulmonary hypertension, the murine pulmonary artery banding, and rat monocrotaline and Sugen5416/hypoxia models. Invasive hemodynamic and echocardiographic assessment was performed on galectin-3 knockout or inhibitor-treated mice. Measurements and Main Results: Established fibrosis was characterized by marked expression of galectin-3 and an enhanced number of proliferating RV fibroblasts. Galectin-3 genetic and pharmacologic inhibition or antifibrotic treatment with pirfenidone significantly diminished RV fibrosis progression in the pulmonary artery banding model, without improving RV functional parameters. RV fibrotic regions were populated with mesenchymal cells coexpressing vimentin and PDGFRα (platelet-derived growth factor receptor-α), but generally lacked αSMA (α-smooth muscle actin) positivity. Serum levels of galectin-3 were increased in patients with idiopathic pulmonary arterial hypertension but did not correlate with cardiac function. No changes of galectin-3 expression were observed in the lungs. Conclusions: We identified extrapulmonary galectin-3 as an important mediator that drives RV fibrosis in pulmonary hypertension through the expansion of PDGFRα/vimentin-expressing cardiac fibroblasts. However, interventions effectively targeting fibrosis lack significant beneficial effects on RV function.


Assuntos
Fibrose/complicações , Fibrose/fisiopatologia , Galectina 3/imunologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia , Animais , Áustria , Baltimore , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Ratos , Função Ventricular Direita/efeitos dos fármacos
19.
Circulation ; 139(14): e801-e813, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30586770

RESUMO

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.


Assuntos
Cardiologia/normas , Fármacos Cardiovasculares/uso terapêutico , Medicina Baseada em Evidências/normas , Cardiopatias Congênitas/tratamento farmacológico , Ventrículos do Coração/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Fármacos Cardiovasculares/efeitos adversos , Consenso , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Adulto Jovem
20.
Respir Res ; 19(1): 258, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567595

RESUMO

BACKGROUND: Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). The objective of this study was to evaluate right heart size and function assessed by echocardiography during long term treatment with riociguat. METHODS: Patients who started riociguat treatment (1.0-2.5 mg tid) within the trials phase II, PATENT, PATENTplus, EAS, CHEST and continued treatment for 3-12 months were included in this study. Echocardiography was analysed off-line at baseline, after 3, 6 and 12 months by investigators who were blinded to clinical data. Last and baseline observation carried forward method (LOCF, BOCF) were performed as sensitivity analysis. RESULTS: Seventy-one patients (45% PAH, 55% CTEPH; 53.5% female; 60 ± 13 years, mean pulmonary arterial pressure 46 ± 10 mmHg, mean PVR 700 ± 282dynes·sec·cm-5) were included. After 6 months, RA and RV area, RV thickness tricuspid regurgitation velocity showed a significant reduction. After 12 months, patients receiving riociguat therapy showed a significant reduction in right atrial (- 2.6 ± 4.4 cm2, 95% CI -3.84, - 1.33; p < 0.001, n = 49) and right ventricular (RV) area (- 3.5 ± 5.2 cm2, 95% CI -5.1, - 1.9; p < 0.001; n = 44), RV thickness (- 0.76 ± 2.2 mm, 95% CI -1.55, 0.03; n = 32), and a significant increase in TAPSE (2.95 ± 4.78 mm, 95% CI 1.52, 4.39; n = 45) and RV fractional area change (8.12 ± 8.87 mm, 95% CI 4.61, 11.62; n = 27). Both LOCF and BOCF showed similar results but lower effect sizes. CONCLUSION: Patients under long-term treatment with riociguat show significantly reduced right heart size and improved RV function in PAH and CTEPH. Further controlled prospective studies are needed to confirm these results.


Assuntos
Ventrículos do Coração/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Função Ventricular Direita/efeitos dos fármacos , Idoso , Doença Crônica , Método Duplo-Cego , Ativadores de Enzimas/farmacologia , Ativadores de Enzimas/uso terapêutico , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Estudos Retrospectivos , Função Ventricular Direita/fisiologia
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