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1.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 72-79, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33899430

RESUMO

Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52% vs. 51.77%, respectively). The systolic period was significantly shorter than the RV systolic period in the continuous-flow mode (LV vs. RV: 24.38% vs. 49.16%) and the LV systolic period at baseline. The LV systolic duration was significantly shorter than the RV systolic duration in the pulse mode (LV vs. RV: 28.38% vs. 50.41%), but longer than the LV systolic duration in the continuous-flow mode. There was no significant difference between the LV and RV systolic periods in the counter-pulse mode (LV vs. RV: 43.13% vs. 49.23%). However, the LV systolic periods was shorter than the no-pump mode and much longer than the continuous-flow mode. Compared with continuous-flow and pulse mode, the reduction in rotational speed (RS) brought out by counter-pulse mode significantly corrected the duration of LV systolic phase. The shortened duration of systolic phase in the continuous-flow mode was corrected as re-synchronization in the counter-pulse mode between LV and RV. Hence, we postulated that the beneficial effects on RV function were due to re-synchronizing of RV and LV contraction. In conclusion, decreased RS delivered during the systolic phase using the counter-pulse mode holds promise for the clinical correction of desynchrony in bi-ventricular pulse resulting from a LVAD and confers a benefit on RV function.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Insuficiência Cardíaca/terapia , Humanos , Sístole , Função Ventricular Direita
4.
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
5.
Am J Physiol Heart Circ Physiol ; 320(4): H1658-H1669, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635163

RESUMO

The goal of this work was to investigate the role of t-tubule (TT) remodeling in abnormal Ca2+ cycling in ventricular myocytes of failing dog hearts. Heart failure (HF) was induced using rapid right ventricular pacing. Extensive changes in echocardiographic parameters, including left and right ventricular dilation and systolic dysfunction, diastolic dysfunction, elevated left ventricular filling pressures, and abnormal cardiac mechanics, indicated that severe HF developed. TT loss was extensive when measured as the density of total cell volume, derived from three-dimensional confocal image analysis, and significantly increased the distances in the cell interior to closest cell membrane. Changes in Ca2+ transients indicated increases in heterogeneity of Ca2+ release along the cell length. When critical properties of Ca2+ release variability were plotted as a function of TT organization, there was a complex, nonlinear relationship between impaired calcium release and decreasing TT organization below a certain threshold of TT organization leading to increased sensitivity in Ca2+ release below a TT density threshold of 1.5%. The loss of TTs was also associated with a greater incidence of triggered Ca2+ waves during rapid pacing. Finally, virtually all of these observations were replicated by acute detubulation by formamide treatment, indicating an important role of TT remodeling in impaired Ca2+ cycling. We conclude that TT remodeling itself is a major contributor to abnormal Ca2+ cycling in HF, reducing myocardial performance. The loss of TTs is also responsible for a greater incidence of triggered Ca2+ waves that may play a role in ventricular arrhythmias arising in HF.NEW & NOTEWORTHY Three-dimensional analysis of t-tubule density showed t-tubule disruption throughout the whole myocyte in failing dog ventricle. A double-linear relationship between Ca2+ release and t-tubule density displays a steeper slope at t-tubule densities below a threshold value (∼1.5%) above which there is little effect on Ca2+ release (T-tubule reserve). T-tubule loss increases incidence of triggered Ca2+ waves. Chemically induced t-tubule disruption suggests that t-tubule loss alone is a critical component of abnormal Ca2+ cycling in heart failure.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Estimulação Cardíaca Artificial , Modelos Animais de Doenças , Cães , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Masculino , Miócitos Cardíacos/patologia , Função Ventricular Esquerda , Função Ventricular Direita , Pressão Ventricular
6.
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
7.
Am J Cardiol ; 144: 137-142, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385349

RESUMO

Although higher body mass index (BMI) is associated with adverse left ventricular morphology and functional remodeling, its possible association with right ventricular (RV) dysfunction has not been extensively evaluated. RV free wall longitudinal strain (RVLS) is emerging as an important tool to detect early RV dysfunction. This study aimed to investigate the independent effect of increased BMI on RVLS in a large sample of the general population without overt cardiac disease. We examined 1,085 participants (603 men, mean age 62 years) who voluntarily underwent an extensive cardiovascular health check-up. This included laboratory tests and speckle-tracking echocardiography to assess RVLS. The association between BMI and RVLS was determined by logistic regression analyses. The prevalence of abnormal RVLS (>-19.2%) was greatest in obese individuals (29.7%), followed by overweight (16.3%), and normal weight (10.6%, p <0.001). In multivariable analyses, BMI was significantly associated with abnormal RVLS (adjusted odds ratio [OR] = 1.07 per 1 kg/m2, p = 0.033) independent of traditional cardiovascular risk factors, pertinent laboratory and echocardiographic parameters including RV size and pulmonary artery systolic pressure. In subgroup analyses, BMI was significantly associated with abnormal RVLS in men (adjusted OR 1.10 per 1 kg/m2, p = 0.032) and younger (<65 years) participants (adjusted OR 1.13 per 1 kg/m2, p = 0.011), but not in women and the elderly. In a sample of the general population, higher BMI was independently associated with subclinical RV dysfunction. Furthermore, an increased BMI may carry different risk for impaired RVLS depending on the age and sex.


Assuntos
Índice de Massa Corporal , Obesidade/epidemiologia , Disfunção Ventricular Direita/epidemiologia , Função Ventricular Direita , Adulto , Fatores Etários , Idoso , Ecocardiografia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sobrepeso/epidemiologia , Fatores Sexuais , Disfunção Ventricular Direita/diagnóstico por imagem
8.
Am J Physiol Heart Circ Physiol ; 320(4): H1261-H1275, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416456

RESUMO

Acute exhaustive endurance exercise can differentially impact the right ventricle (RV) versus the left ventricle (LV). However, the hemodynamic basis for these differences and its impact on postexercise recovery remain unclear. Therefore, we assessed cardiac structure and function along with hemodynamic properties of mice subjected to single bouts (216 ± 8 min) of exhaustive swimming (ES). One-hour after ES, LVs displayed mild diastolic impairment compared with that in sedentary (SED) mice. Following dobutamine administration to assess functional reserve, diastolic and systolic function were slightly impaired. Twenty-four hours after ES, LV function was largely indistinguishable from that in SED. By contrast, 1-h post swim, RVs showed pronounced impairment of diastolic and systolic function with and without dobutamine, which persisted 24 h later. The degree of RV impairment correlated with the time-to-exhaustion. To identify hemodynamic factors mediating chamber-specific responses to ES, LV pressure was recorded during swimming. Swimming initiated immediate increases in heart rates (HRs), systolic pressure, dP/dtmax and -dP/dtmin, which remained stable for ∼45 min. LV end-diastolic pressures (LVEDP) increased to ≥45 mmHg during the first 10 min and subsequently declined. After 45 min, HR and -dP/dtmin declined, which correlated with gradual elevations in LVEDP (to ∼45 mmHg) as mice approached exhaustion. All parameters rapidly normalized postexercise. Consistent with human studies, our findings demonstrate a disproportionate negative impact of acute exhaustive exercise on RVs that persisted for at least 24 h. We speculate that the differential effects of exhaustive exercise on the ventricles arise from a ∼2-fold greater hemodynamic load in the RV than in LV originating from profound elevations in LVEDPs as mice approach exhaustion.NEW & NOTEWORTHY Acute exhaustive exercise differentially impacts the right ventricle (RV) versus left ventricle (LV), yet the underlying hemodynamic basis remains unclear. Using pressure-volume analyses and pressure-telemetry implantation in mice, we confirmed a marked disproportionate and persistent negative impact of exhaustive exercise on the RV. These differences in responses of the ventricles to exhaustive exercise are of clinical relevance, reflecting ∼2-fold greater hemodynamic RV loads versus LVs arising from massive (∼45 mmHg) increases in LV end-diastolic pressures at exhaustion.


Assuntos
Cardiomegalia Induzida por Exercícios , Coração/fisiologia , Hemodinâmica , Resistência Física , Natação , Função Ventricular Esquerda , Função Ventricular Direita , Adaptação Fisiológica , Animais , Masculino , Camundongos , Volume Sistólico , Fatores de Tempo , Pressão Ventricular
9.
Eur J Endocrinol ; 184(2): 289-298, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33513126

RESUMO

Background: Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods: From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results: In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (ß = -12.43, P < 0.001), end-systolic volume (ß = -7.12, P < 0.001), stroke volume (ß = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (ß = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions: Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.


Assuntos
Insulina/sangue , Pulmão/patologia , Função Ventricular Direita/fisiologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Feminino , Alemanha , Testes de Função Cardíaca , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de Risco
10.
Am J Physiol Heart Circ Physiol ; 320(3): H980-H990, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416457

RESUMO

Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and is implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or from weaning through adulthood (420 mmHg, postnatal day 21 through 8 wk). Pulmonary hemodynamics and right ventricular systolic pressure (RVSP) were measured at 8 wk. mTOR pathway proteins were assessed in fetal (day 18.5) and adult lung (8 wk). Perinatal hypoxia induced PH during adulthood, even in the absence of a sustained secondary hypoxic exposure, as indicated by reduced pulmonary artery acceleration time (PAAT) and peak flow velocity through the pulmonary valve, as well as greater RVSP, right ventricular (RV) wall thickness, and RV/left ventricular (LV) weight. Such effects were independent of increased blood viscosity. In fetal lung homogenates, hypoxia reduced the expression of critical downstream mTOR targets, most prominently total and phosphorylated translation repressor protein (4EBP1), as well as vascular endothelial growth factor, a central regulator of angiogenesis in the fetal lung. In contrast, adult offspring of hypoxic dams tended to have elevated p4EBP1 compared with controls. Our data suggest that inhibition of mTORC1 activity in the fetal lung as a result of gestational hypoxia may interrupt pulmonary vascular development and thereby contribute to the developmental programming of PH.NEW & NOTEWORTHY We describe the first study to evaluate a role for the mTOR pathway in the developmental programming of pulmonary hypertension. Our findings suggest that gestational hypoxia impairs mTORC1 activation in the fetal lung and may impede pulmonary vascular development, setting the stage for pulmonary vascular disease in later life.


Assuntos
Hipóxia Fetal/complicações , Hipertensão Pulmonar/etiologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neovascularização Fisiológica , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Feminino , Hipóxia Fetal/metabolismo , Hipóxia Fetal/fisiopatologia , Idade Gestacional , Hemodinâmica , Oxigenação Hiperbárica , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Camundongos Endogâmicos C57BL , Fosforilação , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Circulação Pulmonar , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Direita , Pressão Ventricular
11.
J Thorac Cardiovasc Surg ; 161(3): 1139-1148, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33454101

RESUMO

OBJECTIVE: For children with severe pulmonary hypertension, addition of Potts shunt to a comprehensive palliation strategy might improve the outcomes afforded by medications and delay lung transplantation. METHODS: A prospective analysis was conducted of all children undergoing Potts shunt (first performed in 2013) or bilateral lung transplant for pulmonary hypertension from 1995 to present. RESULTS: A total of 23 children underwent Potts shunt (20 surgical, 3 transcatheter), and 31 children underwent lung transplant. All children with Potts shunt had suprasystemic right ventricle pressures despite maximal medical treatment. In the majority of patients, the Potts shunt was performed through a left thoracotomy approach (90%, 18/20), by direct anastomosis (65%, 13/20), and without the use of extracorporeal support (65%, 13/20). Perioperative outcomes after Potts shunt were superior to lung transplant including mechanical ventilation time (1.3 vs 10.2 days, P = .019), median hospital length of stay (9.8 vs 34 days, P = .012), and overall complication rate (35% [7/20] vs 81% [25/31], P = .003). Risk factors for operative mortality after Potts shunt (20%, 4/20; compared with 6%, 2/31 for lung transplant, P = .195) included preoperative extracorporeal membrane oxygenation and significant right ventricle dysfunction. In midterm follow-up (median 1.8, maximum 6.1 years), patients with Potts shunt had durable equalization of right ventricle/left ventricle pressures and improved functional status. There was no significant survival difference in patients with Potts shunt and patients with lung transplant (P = .258). CONCLUSIONS: Potts shunt is an effective palliation for children with suprasystemic pulmonary hypertension that may become part of a strategy to maximize longevity and functional status for these challenging patients.


Assuntos
Procedimentos Endovasculares , Hipertensão Pulmonar/cirurgia , Transplante de Pulmão , Cuidados Paliativos , Procedimentos Cirúrgicos Vasculares , Fatores Etários , Anastomose Cirúrgica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Hemodinâmica , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Stents , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Função Ventricular Esquerda , Função Ventricular Direita
12.
Am J Physiol Heart Circ Physiol ; 320(3): H1021-H1036, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481696

RESUMO

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated ventricular afterload. We hypothesized that the mechanical stress on the RV associated with increased afterload impairs vasodilator function of the right coronary artery (RCA) in PH. Coronary vascular response was assessed using microangiography with synchrotron radiation (SR) in two well-established PH rat models, monocrotaline injection or the combined exposure to chronic hypoxia and vascular endothelial growth factor receptor blockade with Su5416 (SuHx model). In the SuHx model, the effect of the treatment with the nonselective endothelin-1 receptor antagonist (ERA), macitentan, was also examined. Myocardial viability was determined in SuHx model rats, using 18F-FDG Positron emission tomography (PET) and magnetic resonance imaging (MRI). Endothelium-dependent and endothelium-independent vasodilator responses were significantly attenuated in the medium and small arteries of severe PH rats. ERA treatment significantly improved RCA vascular function compared with the untreated group. ERA treatment improved both the decrease in ejection fraction and the increased glucose uptake, and reduced RV remodeling. In addition, the upregulation of inflammatory genes in the RV was almost suppressed by ERA treatment. We found impairment of vasodilator responses in the RCA of severe PH rat models. Endothelin-1 activation in the RCA plays a major role in impaired vascular function in PH rats and is partially restored by ERA treatment. Treatment of PH with ERA may improve RV function in part by indirectly attenuating right heart afterload and in part by associated improvements in right coronary endothelial function.NEW & NOTEWORTHY We demonstrated for the first time the impairment of vascular responses in the right coronary artery (RCA) of the dysfunctional right heart in pulmonary hypertensive rats in vivo. Treatment with an endothelin-1 receptor antagonist ameliorated vascular dysfunction in the RCA, enabled tissue remodeling of the right heart, and improved cardiac function. Our results suggest that impaired RCA function might also contribute to the early progression to heart failure in patients with severe pulmonary arterial hypertension (PAH). The endothelium of the coronary vasculature might be considered as a potential target in treatments to prevent heart failure in severe patients with PAH.


Assuntos
Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Síncrotrons , Vasodilatação , Disfunção Ventricular Direita/diagnóstico por imagem , Animais , Anti-Hipertensivos/farmacologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina/farmacologia , Endotelina-1/genética , Endotelina-1/metabolismo , Hipertrofia Ventricular Direita/tratamento farmacológico , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Hipóxia/complicações , Indóis , Monocrotalina , Valor Preditivo dos Testes , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Pirimidinas/farmacologia , Pirróis , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Sulfonamidas/farmacologia , Vasodilatação/efeitos dos fármacos , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/metabolismo , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita , Remodelação Ventricular
13.
J Thorac Cardiovasc Surg ; 161(3): 1048-1059.e3, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33485653

RESUMO

OBJECTIVES: Right heart hemodynamic management is critical, because many post-heart transplantation (HTx) complications are related to right ventricular (RV) failure. However, current guidelines on size and sex matching rely primarily on weight matching, with recent literature using total ventricular mass (TVM), which places less emphasis on the impact of RV mass (RVM) matching. The aim of the present study was to analyze the relationship of RVM matching and survival after HTx. METHODS: We performed the retrospective analysis using the UNOS database of adult HTx performed between January 1997 and December 2017. Previously validated equations were used to calculate TVM and RVM. The percent difference in ventricular mass in the donor and recipient pair was used for the size mismatch. All donor-recipient pairs were divided into 4 RVM groups by their mismatch ratio. We analyzed RVM matching and explored how RVM undersizing impacted outcomes. The primary outcome measure was 1-year survival; secondary outcomes measured included stroke and dialysis within 1 year and functional status. RESULTS: A total of 38,740 donor-recipient pairs were included in our study. The 4 RVM match groupings were as follows: <0%, 0% to 20%, 20% to 40%, and >40%. Utilization of donors who were older and of female sex resulted in greater RVM undersizing. Survival analysis demonstrated patients with RVM undersizing had worse 1-year survival (P < .001). RVM undersizing was an independent predictor of higher 1-year mortality (hazard ratio, 1.23; 95% confidence interval, 1.11 to 1.34; P < .001). RVM undersizing was also associated with higher rates of dialysis within 1-year of transplantation and poorer postoperative functional status. CONCLUSIONS: RVM undersizing is an independent predictor for worse 1-year survival. Donors who are older and female have lower absolute predicted RVM and may be predisposed to RVM undersizing. RVM-undersized transplantation requires careful risk/benefit considerations.


Assuntos
Seleção do Doador , Transplante de Coração/mortalidade , Disfunção Ventricular Direita/mortalidade , Função Ventricular Direita , Adulto , Fatores Etários , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Feminino , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
14.
Echocardiography ; 38(2): 222-229, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33368601

RESUMO

AIMS: The aim of this investigation was to evaluate echocardiographic parameters of cardiac function and in particular right ventricular (RV) function as a predictor of mortality in patients with coronavirus disease-2019 (COVID-19) pneumonia. METHODS AND RESULTS: This prospective observational study included 35 patients admitted to a UK district general hospital with COVID-19 and evidence of cardiac involvement, that is, raised Troponin I levels or clinical evidence of heart failure during the first wave of the COVID-19 pandemic (March-May 2020). All patients underwent echocardiography including speckle tracking for right ventricular longitudinal strain (RVLS) providing image quality was sufficient (30 out of 35 patients). Upon comparison of patients who survived COVID-19 with non-survivors, survivors had significantly smaller RVs (basal RV diameter 38.2 vs 43.5 mm P = .0295) with significantly better RV function (Tricuspid annular plane systolic excursion (TAPSE): 17.5 vs 15.3 mm P = .049; average RVLS: 24.3% vs 15.6%; P = .0018). Tricuspid regurgitation (TR) maximal velocity was higher in survivors (2.75 m/s vs 2.11 m/s; P = .0045) indicating that pressure overload was not the predominant driver of this effect and there was no significant difference in left ventricular (LV) ejection fraction. Kaplan-Meier and log-rank analysis of patients split into groups according to average RVLS above or below 20% revealed significantly increased 30-day mortality in patients with average RVLS under 20% (HR: 3.189; 95% CI: 1.297-12.91; P = .0195). CONCLUSION: This study confirms that RVLS is a potent and independent predictor of outcome in COVID-19 patients with evidence of cardiac involvement.


Assuntos
/epidemiologia , Ecocardiografia Tridimensional/métodos , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Pandemias , Volume Sistólico/fisiologia , Função Ventricular Direita/fisiologia , Idoso , Comorbidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Projetos Piloto , Prognóstico , Estudos Prospectivos
15.
Heart Fail Clin ; 17(1): 57-75, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33220887

RESUMO

Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are associated with distinct clinical courses and therapeutic approaches, although they often may coexist. Cardiac magnetic resonance (CMR) provides a noninvasive accurate and reproducible multiplanar anatomic and functional assessment, tissue characterization, and blood flow evaluation of the right heart and pulmonary circulation. This article reviews the current status of the CMR, the most recent techniques, the new parameters and their clinical utility in diagnosis, prognosis, and therapeutic management in the right heart and pulmonary circulation disorders.


Assuntos
Cardiomiopatias/diagnóstico , Hipertensão Pulmonar/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Circulação Pulmonar/fisiologia , Função Ventricular Direita/fisiologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Espectroscopia de Ressonância Magnética
16.
Am J Physiol Heart Circ Physiol ; 320(2): H912-H922, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33337965

RESUMO

Magnetic resonance imaging (MRI) of the right ventricle (RV) offers important diagnostic information, but the accuracy of this information is hampered by the complex geometry of the RV. Here, we propose a novel postprocessing algorithm that corrects for partial-volume effects in the analysis of standard MRI cine images of RV mass (RVm) and evaluate the method in clinical and preclinical data. Self-corrected RVm measurement was compared with conventionally measured RVm in 16 patients who showed different clinical indications for cardiac MRI and in 17 Wistar rats with different degrees of pulmonary congestion. The rats were studied under isoflurane anaesthesia. To evaluate the reliability of the proposed method, the measured end-systolic and end-diastolic RVm were compared. Accuracy was evaluated by comparing preclinical RVm to ex vivo RV weight (RVw). We found that use of the self-correcting algorithm improved reliability compared with conventional segmentation. For clinical data, the limits of agreement (LOAs) were -1.8 ± 8.6g (self-correcting) vs. 5.8 ± 7.8g (conventional), and coefficients of variation (CoVs) were 7.0% (self-correcting) vs. 14.3% (conventional). For preclinical data, LOAs were 21 ± 46 mg (self-correcting) vs. 64 ± 89 mg (conventional), and CoVs were 9.0% (self-correcting) and 17.4% (conventional). Self-corrected RVm also showed better correspondence with the ex vivo RVw: LOAs were -5 ± 80 mg (self-correcting) vs. 94 ± 116 mg (conventional) in end-diastole and -26 ± 74 mg (self-correcting) vs. 31 ± 98 mg (conventional) in end-systole. The new self-correcting algorithm improves the reliability and accuracy of RVm measurements in both clinical and preclinical MRI. It is simple and easy to implement and does not require any additional MRI data.NEW & NOTEWORTHY Magnetic resonance imaging (MRI) of the right ventricle (RV) offers important diagnostic information, but the accuracy of this information is hampered by the complex geometry of the RV. In particular, the crescent shape of the RV renders it particularly vulnerable to partial-volume effects. We present a new, simple, self-correcting algorithm that can be applied to correct partial-volume effects in MRI-based RV mass estimation. The self-correcting algorithm offers improved reliability and accuracy compared with the conventional approach.


Assuntos
Algoritmos , Cardiopatias/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Imagem Cinética por Ressonância Magnética , Função Ventricular Direita , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Cardiopatias/fisiopatologia , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Ratos Wistar , Reprodutibilidade dos Testes
17.
Am J Physiol Heart Circ Physiol ; 320(3): H923-H941, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356960

RESUMO

With each heartbeat, the right ventricle (RV) inputs blood into the pulmonary vascular (PV) compartment, which conducts blood through the lungs at low pressure and concurrently fills the left atrium (LA) for output to the systemic circulation. This overall hemodynamic function of the integrated RV-PV-LA unit is determined by complex interactions between the components that vary over the cardiac cycle but are often assessed in terms of mean pressure and flow. Exercise challenges these hemodynamic interactions as cardiac filling increases, stroke volume augments, and cycle length decreases, with PV pressures ultimately increasing in association with cardiac output. Recent cardiopulmonary exercise hemodynamic studies have enriched the available data from healthy adults, yielded insight into the underlying mechanisms that modify the PV pressure-flow relationship, and better delineated the normal limits of healthy responses to exercise. This review will examine hemodynamic function of the RV-PV-LA unit using the two-element Windkessel model for the pulmonary circulation. It will focus on acute PV and LA responses that accommodate increased RV output during exercise, including PV recruitment and distension and LA reservoir expansion, and the integrated mean pressure-flow response to exercise in healthy adults. Finally, it will consider how these responses may be impacted by age-related remodeling and modified by sex-related cardiopulmonary differences. Studying the determinants and recognizing the normal limits of PV pressure-flow relations during exercise will improve our understanding of cardiopulmonary mechanisms that facilitate or limit exercise.


Assuntos
Função do Átrio Esquerdo , Exercício Físico , Coração/fisiologia , Hemodinâmica , Pulmão/irrigação sanguínea , Circulação Pulmonar , Função Ventricular Direita , Adaptação Fisiológica , Fatores Etários , Feminino , Voluntários Saudáveis , Humanos , Masculino , Modelos Cardiovasculares , Fatores Sexuais , Fatores de Tempo
18.
Am J Physiol Heart Circ Physiol ; 320(3): H1037-H1054, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356963

RESUMO

Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bidirectionally couples the systemic circulation with the LV and coronary perfusion with flow regulation. In the model, coronary flow in the left anterior descending (LAD) and left circumflex (LCX) arteries affects the corresponding regional contractility based on a prescribed linear LV contractility-coronary flow relationship. The model is calibrated with experimental measurements of LV pressure and volume, as well as LAD and LCX flow rate waveforms acquired under regulated and fully dilated conditions from a swine under right atrial (RA) pacing. The calibrated model is applied to simulate MD. The model can simultaneously reproduce the reduction in mean LV pressure (39.3%), regulated flow (LAD: 7.9%; LCX: 1.9%), LAD passive flow (21.6%), and increase in LCX passive flow (15.9%). These changes are associated with right ventricular pacing compared with RA pacing measured in the same swine only when LV contractility is affected by flow alterations with a slope of 1.4 mmHg/mL2 in a contractility-flow relationship. In sensitivity analyses, the model predicts that coronary flow reserve (CFR) decreases and increases in the LAD and LCX with increasing delay in LV free wall contraction. These findings suggest that asynchronous activation associated with MD impacts 1) the loading conditions that further affect the coronary flow, which may explain some of the changes in CFR, and 2) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure.NEW & NOTEWORTHY A computational model that couples the systemic circulation of the left ventricular (LV) and coronary perfusion with flow regulation is developed to study the effects of mechanical dyssynchrony. The delayed contraction in the LV free wall with respect to the septum has a significant effect on LV function and coronary flow reserve.


Assuntos
Estimulação Cardíaca Artificial/efeitos adversos , Circulação Coronária , Modelos Cardiovasculares , Contração Miocárdica , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Função Ventricular Direita , Animais , Simulação por Computador , Modelos Animais de Doenças , Volume Sistólico , Sus scrofa , Fatores de Tempo , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular
19.
Ter Arkh ; 92(9): 24-29, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33346427

RESUMO

AIM: To perform comparative analysis of right ventricular (RV) structure and function in patients with various cardiovascular diseases using modern echocardiographic technologies in comparison with magnetic resonance imaging (MRI). MATERIALS AND METHODS: The study included 85 patients. Group 1 consisted of 32 patients with idiopathic pulmonary hypertension (IPH) (mean age 35.910.2 years). Group 2 included 27 patients with arterial hypertension (AH) grade 3 (mean age 58.612.3 years). Group 3 consisted of 26 patients with chronic heart failure (CHF) (mean age 56.115.3 years). Control group included 28 healthy volunteers (mean age 38.710.9 years). The main method was transthoracic echocardiography (TTE) using modern technologies, such as three-dimensional echocardiography (3DE), tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). In some patients and healthy volunteers 3DE data were compared with MRI data. RESULTS: Patients with IPH and CHF had minimal RV ejection fraction (EF) both according to 3DE and MRI. Correlation analysis revealed close correlation between RV volumes and EF according to 3DE and MRI. Minimal values of systolic indicator STV according to TDI were observed in patients with CHF. In all groups, including control group, the highest values of STV were obtained at the level of the basal segments and the lowest values at the level of apical segments. STE revealed the same pattern as TDI. According to STE minimal RV strain was observed in IPH and CHF groups and significantly differed not only from control group, but also from AH group. CONCLUSION: The lowest values of RV EF and strain were observed in IPH and CHF groups. There were no significant differences in these indicators between the groups, that dictates the need for thorough assessment of RV structure and function not only in patients with precapillary, but also with postcapillary pulmonary hypertension. The results of the study confirm good comparability of 3DE and MRI in assessing RV volumes and EF.


Assuntos
Doenças Cardiovasculares , Disfunção Ventricular Direita , Adulto , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita
20.
Elife ; 92020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320094

RESUMO

Over 1.6 million Americans suffer from significant tricuspid valve leakage. In most cases this leakage is designated as secondary. Thus, valve dysfunction is assumed to be due to valve-extrinsic factors. We challenge this paradigm and hypothesize that the tricuspid valve maladapts in those patients rendering the valve at least partially culpable for its dysfunction. As a first step in testing this hypothesis, we set out to demonstrate that the tricuspid valve maladapts in disease. To this end, we induced biventricular heart failure in sheep that developed tricuspid valve leakage. In the anterior leaflets of those animals, we investigated maladaptation on multiple scales. We demonstrated alterations on the protein and cell-level, leading to tissue growth, thickening, and stiffening. These data provide a new perspective on a poorly understood, yet highly prevalent disease. Our findings may motivate novel therapy options for many currently untreated patients with leaky tricuspid valves.


Assuntos
Matriz Extracelular/metabolismo , Insuficiência Cardíaca/complicações , Hemodinâmica , Insuficiência da Valva Tricúspide/etiologia , Valva Tricúspide/metabolismo , Função Ventricular Esquerda , Função Ventricular Direita , Adaptação Fisiológica , Animais , Modelos Animais de Doenças , Metabolismo Energético , Matriz Extracelular/genética , Matriz Extracelular/patologia , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Regulação da Expressão Gênica , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Masculino , Carneiro Doméstico , Transdução de Sinais , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/fisiopatologia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/metabolismo , Insuficiência da Valva Tricúspide/fisiopatologia
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