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1.
Heart Fail Clin ; 17(3): 415-422, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051973

RESUMO

Heart failure (HF) is an ongoing crisis reaching epidemic proportions worldwide. About 50% of HF patients have a preserved ejection fraction. Invasive hemodynamics have shown varied results in patients who have HF with preserved ejection fraction (HFpEF). This article attempts to summarize the importance of detecting pulmonary vascular remodeling in HFpEF using invasive hemodynamics. Incorporating newer invasive hemodynamic parameters such as diastolic pulmonary gradient, pulmonary arterial compliance, pulmonary vascular resistance, and pulmonary arterial pulsatility index may improve patient selection for studies used in defining advanced therapies and clinical outcomes. Profiling of patients using invasive hemodynamic parameters may lead to better patient selection for clinical research.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Artéria Pulmonar/fisiopatologia , Volume Sistólico/fisiologia , Remodelação Vascular/fisiologia , Resistência Vascular/fisiologia , Insuficiência Cardíaca/diagnóstico , Hemodinâmica , Humanos
2.
Am J Physiol Heart Circ Physiol ; 320(6): H2385-H2400, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989079

RESUMO

Cell-free hemoglobin (CFH) levels are elevated in septic shock and are higher in nonsurvivors. Whether CFH is only a marker of sepsis severity or is involved in pathogenesis is unknown. This study aimed to investigate whether CFH worsens sepsis-associated injuries and to determine potential mechanisms of harm. Fifty-one, 10-12 kg purpose-bred beagles were randomized to receive Staphylococcus aureus intrapulmonary challenges or saline followed by CFH infusions (oxyhemoglobin >80%) or placebo. Animals received antibiotics and intensive care support for 96 h. CFH significantly increased mean pulmonary arterial pressures and right ventricular afterload in both septic and nonseptic animals, effects that were significantly greater in nonsurvivors. These findings are consistent with CFH-associated nitric oxide (NO) scavenging and were associated with significantly depressed cardiac function, and worsened shock, lactate levels, metabolic acidosis, and multiorgan failure. In septic animals only, CFH administration significantly increased mean alveolar-arterial oxygenation gradients, also to a significantly greater degree in nonsurvivors. CFH-associated iron levels were significantly suppressed in infected animals, suggesting that bacterial iron uptake worsened pneumonia. Notably, cytokine levels were similar in survivors and nonsurvivors and were not predictive of outcome. In the absence and presence of infection, CFH infusions resulted in pulmonary hypertension, cardiogenic shock, and multiorgan failure, likely through NO scavenging. In the presence of infection alone, CFH infusions worsened oxygen exchange and lung injury, presumably by supplying iron that promoted bacterial growth. CFH elevation, a known consequence of clinical septic shock, adversely impacts sepsis outcomes through more than one mechanism, and is a biologically plausible, nonantibiotic, noncytokine target for therapeutic intervention.NEW & NOTEWORTHY Cell-free hemoglobin (CFH) elevations are a known consequence of clinical sepsis. Using a two-by-two factorial design and extensive physiological and biochemical evidence, we found a direct mechanism of injury related to nitric oxide scavenging leading to pulmonary hypertension increasing right heart afterload, depressed cardiac function, worsening circulatory failure, and death, as well as an indirect mechanism related to iron toxicity. These discoveries alter conventional thinking about septic shock pathogenesis and provide novel therapeutic approaches.


Assuntos
Hemoglobinas/metabolismo , Pneumonia/metabolismo , Artéria Pulmonar/fisiopatologia , Choque Séptico/metabolismo , Infecções Estafilocócicas/metabolismo , Acidose/metabolismo , Acidose/fisiopatologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cães , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hemoglobinas/farmacologia , Ferro/metabolismo , Ácido Láctico/metabolismo , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Óxido Nítrico/metabolismo , Pneumonia/fisiopatologia , Troca Gasosa Pulmonar , Distribuição Aleatória , Choque Séptico/fisiopatologia , Staphylococcus aureus/crescimento & desenvolvimento
3.
Medicine (Baltimore) ; 100(16): e25621, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879733

RESUMO

ABSTRACT: This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, ß receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/administração & dosagem , Tetrazóis/administração & dosagem , Doença Aguda , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Biomarcadores/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Antagonistas de Hormônios/administração & dosagem , Humanos , Inflamação , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Troponina T/sangue
4.
World J Pediatr Congenit Heart Surg ; 12(2): 213-219, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33684011

RESUMO

BACKGROUND: Surgical pulmonary artery banding (PAB) has been limited in practice because of later requirement for surgical removal or adjustment. The aim of this study is to describe our experience creating a dilatable PAB via transcatheter balloon dilation (TCBD) in congenital heart disease (CHD) patients. METHODS: Retrospective chart review of adjustable PAB-outline anatomical variants palliated and patient outcomes. RESULTS: Sixteen patients underwent dilatable PAB-median age 52 days (range 4-215) and weight 3.12 kg (1.65-5.8). Seven (44%) of the patients were premature, 11 (69%) had ventricular septal defect(s) with pulmonary over-circulation, four (25%) atrioventricular septal defects, and four (25%) single ventricle physiology. Subsequent to the index procedure: five patients have undergone intracardiac complete repair, six patients remain well palliated with no additional intervention, and four single ventricles await their next palliation. One patient died from necrotizing enterocolitis (unrelated to PAB) and one patient required a pericardiocentesis postoperatively. Five patients underwent TCBD of the PAB without complication-Two had one TCBD, two had two TCBD, and another had three TCBD. The median change in saturation was 14% (complete range 6-22) and PAB diameter 1.7 mm (complete range 1.1-5.2). Median time from PAB to most recent outpatient follow-up was 868 days (interquartile range 190-1,079). CONCLUSIONS: Our institution has standardized a PAB technique that allows for transcatheter incremental increases in pulmonary blood flow over time. This methodology has proven safe and effective enough to supplant other institutional techniques of limiting pulmonary blood flow in most patients-allowing for interval growth or even serving as the definitive palliation.


Assuntos
Cardiopatias Congênitas/cirurgia , Cuidados Paliativos/métodos , Artéria Pulmonar/cirurgia , Circulação Pulmonar/fisiologia , Procedimentos Cirúrgicos Vasculares/métodos , Feminino , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Am J Physiol Lung Cell Mol Physiol ; 320(6): L1025-L1037, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33719549

RESUMO

Pulmonary arterial hypertension (PAH) affects more women than men, although affected females tend to survive longer than affected males. This sex disparity in PAH is postulated to stem from the diverse roles of sex hormones in disease etiology. In animal models, estrogens appear to be implicated not only in pathologic remodeling of pulmonary arteries, but also in protection against right ventricular (RV) hypertrophy. In contrast, the male sex hormone testosterone is associated with reduced survival in male animals, where it is associated with increased RV mass, volume, and fibrosis. However, it also has a vasodilatory effect on pulmonary arteries. Furthermore, patients of both sexes show varying degrees of response to current therapies for PAH. As such, there are many gaps and contradictions regarding PAH development, progression, and therapeutic interventions in male versus female patients. Many of these questions remain unanswered, which may be due in part to lack of effective experimental models that can consistently reproduce PAH pulmonary microenvironments in their sex-specific forms. This review article summarizes the roles of estrogens and related sex hormones, immunological and genetical differences, and the benefits and limitations of existing experimental tools to fill in gaps in our understanding of the sex-based variation in PAH development and progression. Finally, we highlight the potential of a new tissue chip-based model mimicking PAH-afflicted male and female pulmonary arteries to study the sex-based differences in PAH and to develop personalized therapies based on patient sex and responsiveness to existing and new drugs.


Assuntos
Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Caracteres Sexuais , Disfunção Ventricular Direita/fisiopatologia , Animais , Hormônios Esteroides Gonadais/farmacologia , Humanos , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , Disfunção Ventricular Direita/patologia
7.
Am J Cardiol ; 148: 138-145, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667451

RESUMO

Chronic pressure-overload induces right ventricular (RV) adaptation to maintain RV-pulmonary arterial (PA) coupling. RV remodeling is frequently associated with secondary tricuspid regurgitation (TR) which may accelerate uncoupling. Our aim is to determine whether the non-invasive analysis of RV-PA coupling could improve risk stratification in patients with secondary TR. A total of 1,149 patients (median age 72[IQR, 63 to 79] years, 51% men) with moderate or severe secondary TR were included. RV-PA coupling was estimated using the ratio between two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). The risk of all-cause mortality across different values of TAPSE/PASP was analyzed with a spline analysis. The cut-off value of TAPSE/PASP to identify RV-PA uncoupling was based on the spline curve analysis. At the time of significant secondary TR diagnosis the median TAPSE/PASP was 0.35 (IQR, 0.25 to 0.49) mm/mm Hg. A total of 470 patients (41%) demonstrated RV-PA uncoupling (<0.31 mm/mm Hg). Patients with RV-PA uncoupling presented more frequently with heart failure symptoms had larger RV and left ventricular dimensions, and more severe TR compared to those with RV-PA coupling. During a median follow-up of 51 (IQR, 17 to 86) months, 586 patients (51%) died. The cumulative 5-year survival rate was lower in patients with RV-PA uncoupling compared to their counterparts (37% vs 64%, p < 0.001). After correcting for potential confounders, RV-PA uncoupling was the only echocardiographic parameter independently associated with all-cause mortality (HR 1.462; 95% CI 1.192 to 1.793; p < 0.001). In conclusion, RV-PA uncoupling in patients with secondary TR is independently associated with poor prognosis and may improve risk stratification.


Assuntos
Mortalidade , Artéria Pulmonar/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Remodelação Ventricular , Idoso , Pressão Sanguínea , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Artéria Pulmonar/fisiopatologia , Medição de Risco , Índice de Gravidade de Doença , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/fisiopatologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia
8.
Transplantation ; 105(4): 711-722, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33760790

RESUMO

BACKGROUND: Pulmonary artery obstruction is an uncommon but significant complication after lung transplantation. Although numerous reports have documented its occurrence, the hemodynamic parameters associated with its presentation and diagnostic considerations remain ill-defined. This systematic review summarizes evidence in the literature surrounding pulmonary artery obstruction after lung transplantation surgery. METHODS: Databases were searched for all articles and abstracts reporting on pulmonary artery obstruction. Data collected included the number of patients studied, patient characteristics, incidences of pulmonary artery obstruction, and timing and imaging modality used for diagnosis. RESULTS: Thirty-four full-text citations were included in this review. The point prevalence of pulmonary artery obstruction was 3.66%. The peak pulmonary artery velocity associated with obstruction was found to be 2.60 ± 0.58 m/s. The diameter of the obstructed pulmonary artery predictive of poor outcomes was noted to be 0.78 ± 0.40 cm. The majority of diagnoses were made in the late postoperative period using pulmonary angiogram and transesophageal echocardiography. Overall, 76% of patients (47 of 62) required emergent procedural reintervention, and 23% of patients (14 of 62) diagnosed with pulmonary artery obstruction died during their hospital stay. CONCLUSIONS: This systematic review underscores the importance of identifying pulmonary artery obstruction immediately after lung transplant surgery. The clinical implications of these results warrant the development of identification and management strategies for early detection of irregularities in pulmonary artery anastomosis in lung transplant patients.


Assuntos
Transplante de Pulmão/efeitos adversos , Artéria Pulmonar/cirurgia , Estenose de Artéria Pulmonar/cirurgia , Adolescente , Adulto , Feminino , Hemodinâmica , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Reoperação , Medição de Risco , Fatores de Risco , Estenose de Artéria Pulmonar/diagnóstico por imagem , Estenose de Artéria Pulmonar/mortalidade , Estenose de Artéria Pulmonar/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Medicine (Baltimore) ; 100(3): e24356, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546070

RESUMO

ABSTRACT: To investigate the characteristics of pulmonary artery distensibility (PAD) in patients with acute pulmonary embolism (APE) and to assess the correlation of PAD with APE severity and right ventricular function. A total of 33 patients who underwent retrospective electrocardiogram (ECG)-gated computed tomography pulmonary angiography (CTPA) with a definite diagnosis of APE were included in the study. According to APE severity, the patients were divided into severe (SPE) and non-severe (NSPE) groups. Data from a control group without APE matching the basic demographics of the APE patients were collected. Pulmonary artery distensibility (PAD) and right ventricular function parameters were compared among the 3 groups, their relationships were investigated, and receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of the above parameters for the diagnosis of APE severity. The PAD values of the control, NSPE, and SPE groups were (7.877 ±â€Š2.637) × 10-3 mm/Hg, (6.050 ±â€Š2.011) × 10-3 mm/Hg, (4.321 ±â€Š1.717) × 10-3 mm/Hg, respectively (P < .01). There were statistically significant differences in right ventricular function parameters among the 3 groups (P < .05). The correlation analysis between PAD and right ventricular function parameters showed a weak negative correlation (r = -0.281--0.392). The area under the ROC curve of PAD was 0.743, the critical value was 4.200, and the sensitivity and specificity were 62.5% and 94.1%, respectively. The PAD obtained by retrospective ECG-gated CTPA could accurately evaluate APE severity and right ventricular function. As the severity of APE increases, PAD decreases, which is helpful to identify patients at high risk of APE.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Artéria Pulmonar/anormalidades , Embolia Pulmonar/fisiopatologia , Função Ventricular Direita/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Embolia Pulmonar/patologia , Curva ROC , Estudos Retrospectivos
10.
Poult Sci ; 100(3): 100877, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33518352

RESUMO

Broiler ascites syndrome (AS), also called pulmonary artery hypertension, is a metabolic disorder that has been observed worldwide in fast-growing broilers. Pulmonary arterial remodeling is a key step in the development of AS. The precise relationship between mRNA and SNP of the pulmonary artery in regulating AS progression remains unclear. In this study, we obtained pulmonary artery tissues from broilers with AS to perform pathologic section and pathologic anatomic observation. SNP, InDel, and mRNA data analysis were carried out using GATK and ANNOVAR software to study the SNP loci of 985 previously reported genes (437 upregulated and 458 downregulated). The pathology results showed that there was a lot of yellow fluid in the abdominal cavity and pericardium, that the ascites cardiac index and hematocrit changed significantly, and that the pulmonary artery had remodeled and become thicker in the disease group. Myocardial sections showed vacuolar degeneration of myocytes and rupture of muscle fibers. In addition, ALDH7A1, IRG1, GGT5, IGSF1, DHX58, USP36, TREML2, SPAG1, CD34, and PLEKHA7 were found to be closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. Taken together, our present study further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression.


Assuntos
Ascite , Galinhas , Polimorfismo de Nucleotídeo Único , Doenças das Aves Domésticas , RNA Mensageiro , Remodelação Vascular , Animais , Ascite/genética , Ascite/fisiopatologia , Ascite/veterinária , Galinhas/genética , Polimorfismo de Nucleotídeo Único/genética , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/fisiopatologia , Artéria Pulmonar/fisiopatologia , RNA Mensageiro/genética , Remodelação Vascular/genética
11.
Am J Physiol Lung Cell Mol Physiol ; 320(5): L770-L784, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33624555

RESUMO

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.


Assuntos
Reprogramação Celular , Hipóxia Fetal/fisiopatologia , Feto/fisiopatologia , Hipóxia/fisiopatologia , Metaboloma , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Artéria Pulmonar/fisiopatologia , Altitude , Animais , Cálcio , Feminino , Idade Gestacional , Gravidez , Ovinos
12.
Med Sci Monit ; 27: e928413, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33531453

RESUMO

BACKGROUND To explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension. MATERIAL AND METHODS A total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-alpha), and mean pulmonary arterial pressure during treatment were compared between the 2 groups. RESULTS At 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-alpha levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention. CONCLUSIONS Beraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.


Assuntos
Epoprostenol/análogos & derivados , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Epoprostenol/farmacologia , Epoprostenol/uso terapêutico , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Citrato de Sildenafila/farmacologia , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos
13.
Clin Exp Hypertens ; 43(4): 328-333, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33541150

RESUMO

Background: To assess the impact of our surgical strategy for the treatment of patients with functional single ventricle and pulmonary hypertension, especially in patients>24 months old.Methods We retrospectively analyzed the clinical data of 97 patients with functional single ventricle and pulmonary hypertension undergoing pulmonary artery banding (PAB) in our hospital between April 2010 and December 2018. The surgical results, transition to Glenn operation and subsequent transition to Fontan operation were analyzed.Results: The 97 patients underwent PAB included 34 patients>24 months old, hospital mortality was 2.1% (2/97). 62 patients underwent the second-stage Glenn operation, and 21 patients underwent third-stage Fontan operation. On competing risk analysis, at 80 months after PAB, 81% had undergone the Glenn operation, and 13% were awaiting the Glenn operation. At 35 months after the Glenn operation, 2% of patients had died, 63% had undergone the Fontan operation, and 36% were awaiting the Fontan operation.Conclusion: PAB is an acceptable strategy for patients with functional single ventricle associated with pulmonary hypertension. Outcomes and results of subsequent Glenn and Fontan procedures are generally good included patients>24 months. Accompanied with unbalanced atrioventricular septal defect for lower ratio of transition to Glenn and Fontan operation.


Assuntos
Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Lactente , Masculino , Artéria Pulmonar/cirurgia , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
14.
Clin Chest Med ; 42(1): 167-177, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33541610

RESUMO

Pulmonary arterial hypertension (PAH) is a disease of progressive pulmonary vascular remodeling due to abnormal proliferation of pulmonary vascular endothelial and smooth muscle cells and endothelial dysfunction. PAH is a multisystem disease with systemic manifestations and complications. This article covers the chronic heart failure syndrome, including the systemic consequences of right ventricle-pulmonary artery uncoupling and neurohormonal activation, skeletal and respiratory muscle effects, systemic endothelial dysfunction and coronary artery disease, systemic inflammation and infection, endocrine and metabolic changes, the liver and gut axis, sleep, neurologic complications, and skin and iron metabolic changes.


Assuntos
Hipertensão Pulmonar , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia
15.
Am J Physiol Heart Circ Physiol ; 320(4): H1526-H1534, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577434

RESUMO

Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective cohort of patients with PH is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 h/day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 wk and a subset was treated with losartan via an osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin II in the RV and lung, this finding was nonsignificant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan affected left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling.NEW & NOTEWORTHY Chronic, inhaled nicotine causes pulmonary hypertension and right ventricular remodeling in mice. Treatment with losartan, an angiotensin II type 1 receptor antagonist, ameliorates nicotine-induced pulmonary hypertension and right ventricular remodeling. This novel finding provides preclinical evidence for the use of renin-angiotensin system-based therapies in the treatment of pulmonary hypertension, particularly in patients with a history of tobacco-product use.


Assuntos
Pressão Arterial , Vapor do Cigarro Eletrônico , Hipertensão Pulmonar/metabolismo , Hipertrofia Ventricular Direita/metabolismo , Nicotina , Artéria Pulmonar/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Função Ventricular Direita , Remodelação Ventricular , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/prevenção & controle , Exposição por Inalação , Losartan/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Transdução de Sinais , Fatores de Tempo , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
16.
Pediatr Cardiol ; 42(3): 628-636, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33394112

RESUMO

Transcatheter patent ductus arteriosus closure (TCPC) is an emerging treatment for low birth weight extremely premature neonates (EPNs). Left pulmonary artery (LPA) and descending aorta (DAO) obstruction are described device-related complications, however, data on mid- and long-term vascular outcomes are lacking. A retrospective analysis of EPNs who underwent successful TCPC at our institution from 03/2013 to 12/2018 was performed. Two-dimensional echocardiography and spectral Doppler velocities from various time points before and after TCPC were used to identify LPA and DAO flow disturbances. A total of 44 EPNs underwent successful TCPC at a median (range) procedural weight of 1150 g (755-2500 g). Thirty-two (73%) patients were closed with the AVP II and 12 (27%) with the Amplatzer Piccolo device. LPA and DAO velocities on average remained within normal limits and improved spontaneously in long-term follow up (26.1 months, range 1-75 months). One patient, who had concerning LPA flow characteristics immediately after device implant (peak velocity 2.6 m/s) developed progressive LPA stenosis requiring stent placement 3 months post-procedure. In the remaining infants, including 7 (16%) who developed LPA and 3 (7%) who developed DAO flow disturbances (range 2-2.4 m/s), all had progressive normalization of flow velocities over time. TCPC can be performed safely in EPNs with a low incidence of LPA and DAO obstruction. In the absence of significant progressive vascular obstruction in the early post-procedure period, mild increases in LPA and DAO flow velocities tend to improve spontaneously and normalize in long-term follow-up.


Assuntos
Cateterismo Cardíaco/métodos , Permeabilidade do Canal Arterial/cirurgia , Aorta Torácica/fisiopatologia , Cateterismo Cardíaco/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Estenose de Artéria Pulmonar/etiologia , Resultado do Tratamento
17.
Comput Methods Biomech Biomed Engin ; 24(6): 653-662, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33427490

RESUMO

The decompensated univentricular circulation is identified as one of the most challenging conditions and the application of the mechanical circulatory support (MCS) devices is proposed as therapeutic option for Fontan failure. Modelling methodologies are reported to identify the optimized types, extent and duration of required hemodynamic support using MCS. The specific parameters of device-body interaction during support of failing Fontan circulation within the design points of dedicated pediatric ventricular assist devices has not been previously defined. In this work, we introduce a mathematical model developed to simulate the interaction between the Fontan single-ventricular circulation and a constant-flow pediatric ventricular assist device (VAD) Sputnik. The interaction is studied at a pump rotor speed of 5000-9000 rpm. This simulation demonstrates that the pump replacing pulmonary ventricle of the heart creates necessary pressure differential between the systemic veins (7 mmHg) and the pulmonary artery (17.3 mmHg). Moreover, it increases the venous return that, according to the Frank-Starling mechanism, increases the stroke volume up to 32 ml/bpm (26 ml/bpm - without using a pump). For the first time, a simulation for the pediatric VAD Sputnik has been carried out. The simulation results confirm pediatric VAD Sputnik can be a possible tool to normalize the Fontan circulation in pediatric patients.


Assuntos
Técnica de Fontan , Coração Auxiliar , Modelos Cardiovasculares , Pré-Escolar , Simulação por Computador , Circulação Coronária/fisiologia , Hemodinâmica , Humanos , Modelos Teóricos , Pressão , Artéria Pulmonar/fisiopatologia , Veias/fisiopatologia
18.
Int J Mol Med ; 47(2): 595-606, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416126

RESUMO

Pulmonary arterial hypertension (PAH) is associated with increased inflammation and abnormal vascular remodeling. Astragaloside IV (ASIV), a purified small molecular saponin contained in the well­know herb, Astragalus membranaceus, is known to exert anti­inflammatory and anti­proliferation effects. Thus, the present study investigated the possible therapeutic effects of ASIV on monocrotaline (MCT)­induced PAH. Rats were administered a single intraperitoneal injection of MCT (60 mg/kg), followed by treatment with ASIV at doses of 10 and 30 mg/kg once daily for 21 days. Subsequently, right ventricle systolic pressure, right ventricular hypertrophy and serum inflammatory cytokines, as well as pathological changes of the pulmonary arteries, were examined. The effects of ASIV on the hypoxia­induced proliferation and apoptotic resistance of human pulmonary artery smooth muscle cells (HPASMCs) and the dysfunction of human pulmonary artery endothelial cells (HPAECs) were evaluated. MCT elevated pulmonary artery pressure and promoted pulmonary artery structural remodeling and right ventricular hypertrophy in the rats, which were all attenuated by both doses of ASIV used. Additionally, ASIV prevented the increase in the TNF­α and IL­1ß concentrations in serum, as well as their gene expression in lung tissues induced by MCT. In in vitro experiments, ASIV attenuated the hypoxia­induced proliferation and apoptotic resistance of HPASMCs. In addition, ASIV upregulated the protein expression of p27, p21, Bax, caspase­9 and caspase­3, whereas it downregulated HIF­1α, phospho­ERK and Bcl­2 protein expression in HPASMCs. Furthermore, in HPAECs, ASIV normalized the increased release of inflammatory cytokines and the increased protein levels of HIF­1α and VEGF induced by hypoxia. On the whole, these results indicate that ASIV attenuates MCT­induced PAH by improving inflammation, pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and resistance to apoptosis.


Assuntos
Hipertensão Pulmonar , Monocrotalina/toxicidade , Artéria Pulmonar/fisiopatologia , Saponinas/farmacologia , Triterpenos/farmacologia , Remodelação Vascular/efeitos dos fármacos , Animais , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley
19.
Pediatr Cardiol ; 42(4): 736-742, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33512547

RESUMO

Pulmonary hypertension (PH) can lead to progressive heart failure with high morbidity and mortality. Cardiac catheterization (CC) is the gold standard for diagnosis and response to vasodilatory medications. The invasive nature of CC and associated anesthesia predispose this patient population to adverse events including death. Catheterization records were queried from 1/1/2011 to 10/31/2016. Patients with PH, defined as pulmonary vascular resistance (PVR) greater than 3 WU m2, pulmonary artery pressure above 20 mmHg, and pulmonary wedge pressure less than or equal to 15 mmHg, who underwent hemodynamic CC were included in this retrospective study. Both patients with and without congenital heart disease were included. There were 198 CC in 191 patients. Adverse events (n = 28, 14.1%) included cardiac arrest, increased respiratory support requiring ICU care, PH crisis, bradycardia/hypotension requiring intervention, and arrhythmias. Odds of an adverse event increased by 22% for every 15-min increase in procedure times (OR 1.22, CI 1.01-1.39, p = 0.002) and were significantly increased for procedures longer than 80 min (OR 3.75, CI 1.56-9.00, p = 0.007) (Fig. 1). Patients with an adverse event had higher mean pulmonary artery pressures while breathing oxygen (43 [35-58] versus 34 [27-44] mmHg, p = 0.017) and oxygen with inhaled nitric oxide (37 [32-56] versus 32 [25-40] mmHg, p = 0.026). Females carried more risk than males (OR 3.88, CI 1.44-10.40, p = 0.007). Younger age, medication regimens, prematurity, and genetic disease did not carry an increased risk. Adverse events are common in pediatric patients with PH undergoing CC. The risk of adverse events correlates with greater procedure times and higher mean pulmonary artery pressure. Minimizing procedure time may improve patient outcomes.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Anestesia/efeitos adversos , Cateterismo Cardíaco/métodos , Criança , Pré-Escolar , Feminino , Parada Cardíaca/epidemiologia , Parada Cardíaca/etiologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Hemodinâmica , Humanos , Hipertensão Pulmonar/mortalidade , Lactente , Masculino , Óxido Nítrico , Artéria Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resistência Vascular
20.
BMC Cardiovasc Disord ; 21(1): 56, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509091

RESUMO

INTRODUCTION: The absence of a pulmonary artery is a rare congenital anomaly that occurs isolated or with other congenital cardiac disorders, particularly tetralogy of Fallot (TOF); meanwhile, a hidden pulmonary artery might exist and originate from a closed ductus arteriosus (DA), which can be stented to reach the artery. MATERIAL AND METHODS: This prospective study describes cardiac catheterization of nine TOF patients diagnosed with the absence of the left pulmonary artery before the operation. The patients were stratified into three groups: group one, whose closed DA was found and connected to the hidden pulmonary artery with a stent; group two, whose hidden pulmonary arteries were found via the pulmonary vein angiography; and group three, for whom we could not find the remnant of the DA, or our attempt to stent the DA to the hidden pulmonary artery was not successful. We also evaluated outcomes of six other surgically-corrected TOF patients who were operated with the absent left pulmonary artery. RESULTS: The first group included the patients aged 1, 24, and 30 months, whose CT angiography 6-9 months after stenting showed acceptable left pulmonary artery diameter for surgical correction, and the pulmonary vein angiography of the second group showed a hidden left pulmonary artery with a suitable diameter for surgical correction. However, we were unable to find or stent the DA of group three patients, aged 12, 38, 60, and 63 months. Earlier Angiography might have increased the chance of access to the hidden vessel. Apart from these three groups, follow-ups of six other patients previously corrected with only the right pulmonary artery revealed pulmonary artery hypertension in all patients. CONCLUSION: The concealed pulmonary artery might be found, and stenting of the closed DA to it might be performed to improve the diameter of the diminutive pulmonary artery. This procedure may allow TOF total surgical correction with two pulmonary arteries. Besides, pulmonary vein angiography can reveal the hidden pulmonary artery.


Assuntos
Pressão Arterial , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos , Permeabilidade do Canal Arterial/terapia , Artéria Pulmonar/cirurgia , Tetralogia de Fallot/cirurgia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pré-Escolar , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/anormalidades , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Stents , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
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