Ghrelin therapy improves lung and cardiovascular function in experimental emphysema.

BACKGROUND: Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance. Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema. METHODS: Forty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA). In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. C animals (n=20) received saline alone (50 µL) using the same protocol. Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks. Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed. RESULTS: In elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-ß, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass. CONCLUSION: In the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass. These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema.

Effects of time-controlled adaptive ventilation on cardiorespiratory parameters and inflammatory response in experimental emphysema.

The time-controlled adaptive ventilation (TCAV) method attenuates lung damage in acute respiratory distress syndrome. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury (VILI) and cardiac function in emphysema. We hypothesized that the use of the TCAV method to achieve an expiratory flow termination/expiratory peak flow (EFT/EPF) of 25% could reduce VILI and improve right ventricular function in elastase-induced lung emphysema in rats. Five weeks after the last intratracheal instillation of elastase, animals were anesthetized and mechanically ventilated for 1 h using TCAV adjusted to either EFT/EPF 25% or EFT/EPF 75%, the latter often applied in acute respiratory distress syndrome (ARDS). Pressure-controlled ventilation (PCV) groups with positive end-expiratory pressure levels similar to positive end-release pressure in TCAV with EFT/EPF 25% and EFT/EPF 75% were also analyzed. Echocardiography and lung ultrasonography were monitored. Lung morphometry, alveolar heterogeneity, and biological markers related to inflammation [interleukin 6 (IL-6), CINC-1], alveolar pulmonary stretch (amphiregulin), lung matrix damage [metalloproteinase 9 (MMP-9)] were assessed. EFT/EPF 25% reduced respiratory system peak pressure, mean linear intercept, B lines at lung ultrasonography, and increased pulmonary acceleration time/pulmonary ejection time ratio compared with EFT/EPF 75%. The volume fraction of mononuclear cells, neutrophils, and expression of IL-6, CINC-1, amphiregulin, and MMP-9 were lower with EFT/EPF 25% than with EFT/EPF 75%. In conclusion, TCAV with EFT/EPF 25%, compared with EFT/EPF 75%, led to less lung inflammation, hyperinflation, and pulmonary arterial hypertension, which may be a promising strategy for patients with emphysema.NEW & NOTEWORTHY The TCAV method reduces lung damage in ARDS. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury and cardiac function in experimental emphysema. The TCAV method at EFT/EPF ratio of 25%, compared with EFT/EPF of 75% (frequently used in ARDS), reduced lung inflammation, alveolar heterogeneity and hyperinflation, and pulmonary arterial hypertension in elastase-induced emphysema. TCAV may be a promising and personalized ventilation strategy for patients with emphysema.

Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology.

BACKGROUND: The diaphragm is the primary muscle of inspiration, and its dysfunction is frequent during sepsis. However, the mechanisms associated with sepsis and diaphragm dysfunction are not well understood. In this study, we evaluated the morphophysiological changes of the mitochondrial diaphragm 5 days after sepsis induction. METHODS: Male C57Bl/6 mice were divided into two groups, namely, cecal ligation and puncture (CLP, n = 26) and sham-operated (n = 19). Mice received antibiotic treatment 8 h after surgery and then every 24 h until 5 days after surgery when mice were euthanized and the diaphragms were collected. Also, diaphragm function was evaluated in vivo by ultrasound 120 h after CLP. The tissue fiber profile was evaluated by the expression of myosin heavy chain and SERCA gene by qPCR and myosin protein by using Western blot. The Myod1 and Myog expressions were evaluated by using qPCR. Diaphragm ultrastructure was assessed by electron microscopy, and mitochondrial physiology was investigated by high-resolution respirometry, Western blot, and qPCR. RESULTS: Cecal ligation and puncture mice developed moderated sepsis, with a 74% survivor rate at 120 h. The diaphragm mass did not change in CLP mice compared with control, but we observed sarcomeric disorganization and increased muscle thickness (38%) during inspiration and expiration (21%). Septic diaphragm showed a reduction in fiber myosin type I and IIb mRNA expression by 50% but an increase in MyHC I and IIb protein levels compared with the sham mice. Total and healthy mitochondria were reduced by 30% in septic mice, which may be associated with a 50% decrease in Ppargc1a (encoding PGC1a) and Opa1 (mitochondria fusion marker) expressions in the septic diaphragm. The small and non-functional OPA1 isoform also increased 70% in the septic diaphragm. These data suggest an imbalance in mitochondrial function. In fact, we observed downregulation of all respiratory chain complexes mRNA expression, decreased complex III and IV protein levels, and reduced oxygen consumption associated with ADP phosphorylation (36%) in CLP mice. Additionally, the septic diaphragm increased proton leak and downregulated Sod2 by 70%. CONCLUSION: The current model of sepsis induced diaphragm morphological changes, increased mitochondrial damage, and induced functional impairment. Thus, diaphragm damage during sepsis seems to be associated with mitochondrial dysfunction.

Niclosamide attenuates lung vascular remodeling in experimental pulmonary arterial hypertension.

Despite advances in medical therapy, pulmonary arterial hypertension (PAH) remains an inexorably progressive and highly lethal disease. Signal transducer and activator of transcription (STAT)-3 is one of the main intracellular transcription factors implicated in PAH vascular remodeling. We hypothesized that niclosamide, a STAT3 inhibitor, would reduce vascular remodeling in an established pulmonary arterial hypertension model, thus enhancing cardiac function. Male Wistar rats were treated either with monocrotaline (60 mg/kg), to induce PAH, or saline (C group) by intraperitoneal injection. On day 14, PAH animals were randomly assigned to receive oral (1) saline (PAH-SAL); (2) niclosamide (75 mg/kg/day) (PAH-NICLO); (3) sildenafil (20 mg/kg/day) (PAH-SIL); or (4) niclosamide + sildenafil (PAH-NICLO + SIL), once daily for 14 days. On day 28, right ventricular systolic pressure was lower in all treated groups compared to PAH-SAL. Pulmonary vascular collagen content was lower in PAH-NICLO (37 ± 3%) and PAH-NICLO + SIL (37 ± 6%) compared to PAH-SAL (68 ± 4%), but not in PAH-SIL (52 ± 1%). CD-34, an endothelial cell marker, was higher, while vimentin, a mesenchymal cell marker, was lower in PAH-NICLO and PAH-NICLO + SIL compared to PAH-SAL, suggesting attenuation of endothelial-mesenchymal transition. Expression of STAT3 downstream targets such as transforming growth factor (TGF)-ß, hypoxia-inducible factor (HIF)-1, and provirus integration site for Moloney murine leukemia virus (PIM-1) in lung tissue was reduced in PAH-NICLO and PAH-NICLO + SIL compared to PAH-SAL. In conclusion, niclosamide, with or without sildenafil, mitigated vascular remodeling and improved right ventricle systolic pressure. This new role for a well-established drug may represent a promising therapy for PAH.

Endotoxin-Induced Emphysema Exacerbation: A Novel Model of Chronic Obstructive Pulmonary Disease Exacerbations Causing Cardiopulmonary Impairment and Diaphragm Dysfunction.

Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma which also involves extrapulmonary manifestations, such as cardiovascular impairment, diaphragm dysfunction, and frequent exacerbations. The development of animal models is important to elucidate the pathophysiology of COPD exacerbations and enable analysis of possible therapeutic approaches. We aimed to characterize a model of acute emphysema exacerbation and evaluate its consequences on the lung, heart, and diaphragm. Twenty-four Wistar rats were randomly assigned into one of two groups: control (C) or emphysema (ELA). In ELA group, animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. The C group received saline under the same protocol. Five weeks after the last instillation, C and ELA animals received saline (SAL) or E. coli lipopolysaccharide (LPS) (200 µg in 200 µl) intratracheally. Twenty-four hours after saline or endotoxin administration, arterial blood gases, lung inflammation and morphometry, collagen fiber content, and lung mechanics were analyzed. Echocardiography, diaphragm ultrasonography (US), and computed tomography (CT) of the chest were done. ELA-LPS animals, compared to ELA-SAL, exhibited decreased arterial oxygenation; increases in alveolar collapse (p < 0.0001), relative neutrophil counts (p = 0.007), levels of cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and vascular endothelial growth factor in lung tissue, collagen fiber deposition in alveolar septa, airways, and pulmonary vessel walls, and dynamic lung elastance (p < 0.0001); reduced pulmonary acceleration time/ejection time ratio, (an indirect index of pulmonary arterial hypertension); decreased diaphragm thickening fraction and excursion; and areas of emphysema associated with heterogeneous alveolar opacities on chest CT. In conclusion, we developed a model of endotoxin-induced emphysema exacerbation that affected not only the lungs but also the heart and diaphragm, thus resembling several features of human disease. This model of emphysema should allow preclinical testing of novel therapies with potential for translation into clinical practice.

Effects of the FGF receptor-1 inhibitor, infigratinib, with or without sildenafil, in experimental pulmonary arterial hypertension.

BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality, despite advances in medical therapy. We compared the effects of infigratinib (NVP-BGJ398), a new FGF receptor-1 inhibitor, with or without the PDE-5 inhibitor sildenafil, on vascular function and remodelling as well as on gene expression of signal transducers for receptors of TGF-ß (Smads-1/2/4) and transcription factor of endothelial-mesenchymal transition (Twist-1) in established experimental PAH. Types I and III pro-collagen and TGF-ß expressions in lung fibroblasts were analysed in vitro after the different treatments. EXPERIMENTAL APPROACH: PAH was induced in male Wistar rats with monocrotaline. 14 days later, treatments [sildenafil (SIL), infigratinib (INF) or their combination (SIL+INF)] were given for another 14 days. On Day 28, echocardiography and haemodynamic assays were performed, and lungs and pulmonary vessels were removed for analysis by histology, immunohistochemistry and RT-PCR. Fibroblasts prepared from PAH lungs were also analysed for TGF-ß and pro-collagen. KEY RESULTS: Only the combination of infigratinib and sildenafil significantly improved right ventricular systolic pressure and vascular remodelling parameters (right ventricular hypertrophy, smooth muscle α-actin, vessel wall thickness, and vascular collagen content). Infigratinib may act by reducing gene expression of Smads-1/4 and Twist-1 in lung tissue, as well as TGF-ß and types I and III pro-collagen in lung fibroblasts. CONCLUSIONS AND IMPLICATIONS: In this model of monocrotaline-induced PAH, the combination of the new inhibitor of FGF receptor-1, infigratinib, and sildenafil effectively improved haemodynamics and decreased vascular remodelling.

Assessment of the ventricular function of patients with advanced chronic obstructive pulmonary disease by using magnetic resonance imaging.

OBJECTIVE: To assess the mechanisms that may be involved in the evolution of right and left ventricular dysfunction in patients with chronic obstructive pulmonary disease (COPD). METHODS: Magnetic resonance imaging was used in 11 control patients (group C) and 27 patients with COPD, who were divided into 2 groups, COPDc and COPDs, according to the presence or absence of right ventricular dysfunction, respectively. Doppler echocardiography was used for assessing the degree of pulmonary hypertension. RESULTS: The right ventricular diameter was similar in the 3 groups, COPDs, COPDc and C (29+/-8 mm; 31+/-7 mm; and 30+/-6 mm; respectively, P=NS). Right ventricular hypertrophy was observed only in the COPD groups (8+/-2 mm and 9+/-3 mm vs 5+/-1 mm; P<0.01). The percentage of systolic right ventricular lateral wall thickening (%RVLWT) in the 3 groups were as follows: 86+/-82% vs 41+/-35% vs 86+/-89%; P=NS). Different left ventricular ejection fractions were observed in the groups as follows: 69+/-9% vs 55+/-16% vs 76+/-6%; P < 0.01. A positive and significant linear correlation was observed between the left ventricular (LV) diastolic diameter and the LV systolic volume (r = 0.72; P < 0.01). No correlation was observed between the pulmonary volumes, arterial blood gas analysis, and ventricular function. CONCLUSION: No correlation was observed between the severity of pulmonary function and the degree of ventricular function impairment. Whether a preserved %RVLWT means the possibility of reversibility of right ventricular function remains to be elucidated. However, the presence of the phenomenon of ventricular interdependence was confirmed.

Improvement in left ventricular dysfunction after surgical correction of mitral regurgitation.

OBJECTIVE: To evaluate whether left ventricular end-systolic (ESD) diameters < or = 51mm in patients (pt) with severe chronic mitral regurgitation (MR) are predictors of a poor prognosis after mitral valve surgery (MVS). METHODS: Eleven pt (aged 36 +/- 13 years) were studied in the preoperative period (pre), median of 36 days; in the early postoperative period (post1), median of 9 days; and in the late postoperative period (post2), mean of 38.5 +/- 37.6 months. Clinical and echocardiographic data were gathered from each pt with MR and systolic diameter > or = 51 mm (mean = 57 +/- 4mm) to evaluate the result of MVS. Ten patients were in NYHA Class III/IV. RESULTS: All but 2 pt improved in functional class. Two pt died from heart failure and infectious endocarditis 14 and 11 months, respectively, after valve replacement. According to ejection fraction (EF) in post2, we identified 2 groups: group 1 (n=6), whose EF decreased in post1, but increased in post2 (p=0.01) and group 2 (n=5), whose EF decreased progressively from post1 to post2 (p=0.10). All pt with symptoms lasting < or = 48 months had improvement in EF in post2 (p=0.01). CONCLUSION: ESD > or = 51 mm are not always associated with a poor prognosis after MVS in patients with MR. Symptoms lasting up to 48 months are associated with improvement in left ventricular function.

A novel Ca2+ channel antagonist reverses cardiac hypertrophy and pulmonary arteriolar remodeling in experimental pulmonary hypertension.

This work investigates the actions of LASSBio-1289, (E)-N-methyl-N'-(thiophen-3-methylene)benzo[d][1,3]dioxole-5-carbohydrazide, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Two weeks following the MCT injection, LASSBio-1289 (50 or 75mg/kg, p.o.) or vehicle was administrated once daily for 14 days. LASSBio-1289 (75 mg/kg) treatment caused a significant decrease in right ventricular systolic pressure (31.89±0.82 mmHg) compared to the MCT-vehicle group (52.74±6.19 mmHg; P<0.05). Oral treatment with LASSBio-1289 (50 or 75 mg/kg) effectively decreased pulmonary artery diameter and right ventricle (RV) area, assessed by echocardiography. LASSBio-1289 (75 mg/kg) reduced RV area (10.00±0.58 mm(2)) compared to the MCT-vehicle group (20.50±1.44 mm(2); P<0.05). LASSBio-1289 (75 mg/kg) also partially recovered the pulmonary artery acceleration time in MCT-treated rats. Oral treatment with LASSBio-1289 (50mg/kg) decreased the pulmonary arteriolar wall thickness (68.57±2.21%) compared to the MCT-vehicle group (81.07±1.92%; P<0.05). In experiments with isolated pulmonary arteries, the concentration of LASSBio-1289 necessary to produce 50% relaxation in the phenylephrine- or KCl-induced contraction was 27.31±6.94 and 2.72±0.99 µM, respectively, P<0.05. In the presence of LASSBio-1289 (50 µM), the maximal contraction induced by 10mM CaCl2 was reduced to 36.00±8.28% of the maximal contraction of the control curve (P<0.05). LASSBio-1289 was effective in attenuating MCT-induced PAH in rats, and its beneficial effects were likely mediated by the inhibition of extracellular Ca(2+) influx through L-type voltage-gated Ca(2+) channels in the pulmonary artery.

Envelhecimento e alterações cardíacas, bioquímica, moleculares e funcionais: estudo experimental / Aging and Cardiac, Biochemical, Molecular and functional changes: an experimental study

Fundamentos: O envelhecimento abrange mudanças físicas e psicológicas que reduzem a capacidade de adaptação do idoso à sociedade, sendo o maior fator de risco para doenças cardiovasculares. Objetivo: Investigar alterações do sistema cardiovascular decorrentes do processo de envelhecimento em ratos. Métodos: Parâmetros murinométricos/nutricionais, ecocardiográficos e hemodinâmicos foram determinados em ratos machos com um, cinco e 12 meses de idade. A expressão de proteínas importantes na dinâmica do cálcio intracelular ena sinalização da leptina foram investigadas em homogenato de coração de rato, bem como a atividade das ATPases cardíacas. Os dados foram apresentados como média±erro-padrão e analisados pelo teste one way ANOVA (*p<0,05 vs. 1 mês e #p<0,05 vs. 5 meses). Resultados: Enquanto o índice de massa corporal aumentou (0,46±0,01 g/cm2 ; 0,75±0,01 g/cm2*; 0,78±0,01 g/cm2*), ocoeficiente de eficácia alimentar (0,431±0,013; 0,035±0,003*; 0,003±0,001*#), a velocidade máxima desenvolvida em teste de esforço (3,36±0,34 km/h; 1,38±0,04 km/h*;1,20±0,13 km/h*) e a frequência cardíaca (410,2±5,9 bpm; 375,9±7,6 bpm*;376,6±3,3 bpm*) diminuíram com a idade. Foram observadas hipertrofia do ventrículo esquerdo e disfunção diastólicaem paralelo à redução da expressão do receptor para leptina (2,1±0,4; 1,9±0,2; 0,8±0,2*#) e da atividade da bomba decálcio da família SERCA (1981±77 nmol Pi/mg de proteína/h; 2385±205 nmol Pi/mg de proteína/h; 1148±152 nmol Pi/mg de proteína/h#) no coração.Conclusões: O envelhecimento está associado a risco cardiometabólico, sendo a infrarregulação de receptores para leptina e a redução da atividade da bomba de cálcio no coração provavelmente mecanismos subjacentes à disfunção diastólica do ventrículo esquerdo e a consequente intolerância ao exercício.

Background: Aging involves physical and psychological changes that reduce the elderly’s ability to adapt themselves to society, which is the leading risk factor for cardiovascular diseases. Objective: To investigate changes in the cardiovascular system resulting from the aging process in rats. Methods: Murinometric/nutritional, echocardiographic and hemodynamic parameters were determined in 1, 5 and 12-month aged male rats. The expression of proteins that are critical to intracellular calcium dynamics and leptin signaling, as well as cardiac ATPase activity, was investigated in cardiac homogenates of rats. Data were expressed as mean ± standard error and analyzed by ANOVA one-way test (* p <0.05 vs. one month and #p <0.05 vs. 5 months). Results: Whereas the body mass index increased (0.46±0.01 g/cm2; 0.75±0.01 g/cm2 *,0.78±0.01 g/cm2*), the food efficiency ratio(0.431±0.013; 0.035±0.003*; 0.003±0.001*#), maximum speed during maximal exercise stress testing (3.36±0.34 km/h; 1.38±0.04 km/h*;1.20±0.13 km/h*) and heart rate (410.2±5.9bpm; 375.9±7.6 bpm*; 376.6±3,3 bpm*) decreased with age. Left ventricular hypertrophy and diastolic dysfunction along with reduced leptin receptor expression (2.1±0.4; 1.9±0.2; 0.8±0.2*#) and SERCA-type calcium pump activity (1981±77 nmol Pi/mg protein/h; 2385±205 nmol Pi/mg protein/h; 1148±152 nmol Pi/mg protein/h#) were observed in the hearts.Conclusions: Aging process is related to cardiometabolic risk, with cardiac leptin receptor downregulation and reduced cardiac SERCA2 calcium pump activity presumably being mechanisms underlying the left ventricular diastolic dysfunction and consequent exercise intolerance.

Up-regulation of angiotensin-converting enzyme and angiotensin II type 1 receptor in irradiated rats.

PURPOSE: To investigate changes in cardiac functional parameters and the cardiac expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1), procollagen type I (proc-I) and transforming growth factor-ß1 (TGF-ß1) in rats irradiated at heart. MATERIAL AND METHODS: Male Wistar rats were irradiated with a single dose of radiation (0, 5, 10 and 15 Gray [Gy]) delivered directly to the heart and the molecular evaluations were performed at various times post-irradiation (two days, 15 days and four months). The expression of ACE, AT1, proc-I and TGF-ß1 were analysed using Real Time-Polymerase Chain Reaction (RT-PCR) and/or Western blotting. Cardiac structural and functional alterations were investigated at the four-month time point by echocardiography and by quantitative methods (stereology). RESULTS: Rats irradiated with 15 Gy showed a modest reduction in the ejection fraction. Cardiac proc-I, TGF-ß1, ACE and AT1 were also measurably increased. CONCLUSIONS: Irradiated rat hearts show simultaneous elevations in renin-angiotensin system components AT1 and ACE and cardiac remodeling markers proc-I and TGF-ß1.

Efeito Agudo da Pressao Positiva Continua sobre a Pressao de Pulso na Insuficiencia Cardiaca Cronica / Acute Effects of Continuous Positive Air way Pressure on Pulse Pressure in Chronic Heart Failure

Fundamento: Pacientes com insuficiência cardíaca (IC) apresentam disfunção ventricular esquerda e redução da pressão arterial média (PAM). O aumento do estímulo adrenérgico causa vasoconstrição e resistência dos vasos, mantendo a PAM, enquanto aumenta a resistência vascular periférica e a rigidez dos vasos condutores. O aumento da pressão de pulso (PP) reflete a complexa interação do coração com os sistemas arteriais e venosos. O aumento da PP é um importante marcador de risco em pacientes com insuficiência cardíaca crônica (ICC). A ventilação não invasiva (VNI) tem sido utilizada para IC aguda descompensada para melhorar a congestão e a ventilação pelos efeitos respiratórios e hemodinâmicos. No entanto, nenhum desses estudos relatou o efeito da VNI na PP. Objetivo: O objetivo deste estudo foi determinar os efeitos agudos da VNI com CPAP (pressão positiva contínua nas vias aéreas) sobre a PP em pacientes ambulatoriais com ICC. Métodos: Seguindo um protocolo randomizado, duplo-cego, cruzado e controlado com placebo, 23 pacientes com ICC (17 homens, 60 ± 11 anos, IMC 29 ± 5 kg/cm2, classes II e III da NYHA) foram submetidos à CPAP via máscara nasal durante 30 minutos na posição reclinada. A pressão da máscara foi de 6 cmH2O, enquanto o placebo foi fixado em 0-1 cmH2O. PP e outras variáveis hemodinâmicas não invasivas foram avaliadas antes, durante e depois do placebo e do modo CPAP. Resultados: A CPAP diminuiu a frequência cardíaca de repouso (pré: 72 ± 9; pós 5 min: 67 ± 10 bpm , p < 0,01) e PAM (CPAP: 87 ± 11; controle 96 ± 11 mmHg , p < 0,05 pós 5 min). A CPAP diminuiu a PP (CPAP: 47 ± 20 pré para 38 ± 19 mmHg pós; controle: ...

Background: Patients with heart failure (HF) have left ventricular dysfunction and reduced mean arterial pressure (MAP). Increased adrenergic drive causes vasoconstriction and vessel resistance maintaining MAP, while increasing peripheral vascular resistance and conduit vessel stiffness. Increased pulse pressure (PP) reflects a complex interaction of the heart with the arterial and venous systems. Increased PP is an important risk marker in patients with chronic HF (CHF). Non-invasive ventilation (NIV) has been used for acute decompensated HF, to improve congestion and ventilation through both respiratory and hemodynamic effects. However, none of these studies have reported the effect of NIV on PP. Objective: The objective of this study was to determine the acute effects of NIV with CPAP on PP in outpatients with CHF. Methods: Following a double-blind, randomized, cross-over, and placebo-controlled protocol, twenty three patients with CHF (17 males; 60 ± 11 years; BMI 29 ± 5 kg/cm2, NYHA class II, III) underwent CPAP via nasal mask for 30 min in a recumbent position. Mask pressure was 6 cmH2O, whereas placebo was fixed at 0-1 cmH2O. PP and other non invasive hemodynamics variables were assessed before, during and after placebo and CPAP mode. Results: CPAP decreased resting heart rate (Pre: 72 ± 9; vs. Post 5 min: 67 ± 10 bpm; p < 0.01) and MAP (CPAP: 87 ± 11; vs. control 96 ± 11 mmHg; p < 0.05 post 5 min). CPAP decreased PP (CPAP: 47 ± 20 pre to 38 ± 19 mmHg post; vs. control: 42 ± 12 mmHg, pre to 41 ± 18 post p < 0.05 post 5 min). Conclusion: NIV with CPAP decreased pulse pressure in patients with stable CHF. Future clinical trials should investigate whether this effect is associated with improved clinical outcome. .

Análise da função ventricular de pacientes com doença pulmonar obstrutiva crônica avançada pela ressonância magnética / Assessment of the ventricular function of patients with advanced chronic obstructive pulmonary disease by using magnetic resonance imaging

OBJETIVO: Avaliar os possíveis mecanismos envolvidos na evolução da disfunção ventricular direita e esquerda em pacientes com doença pulmonar obstrutiva crônica (DPOC). MÉTODOS: A ressonância magnética foi aplicada em 27 pacientes com DPOC divididos em grupos, DPOCc e DPOCs, de acordo com a presença ou ausência de disfunção ventricular direita, respectivamente, e 11 controles (grupo C). O exame Doppler ecocardiográfico foi empregado para análise do grau de hipertensão pulmonar. RESULTADOS: O diâmetro do ventrículo direito foi similar nos 3 grupos, DPOCs, DPOCc e C, 29±8 mm vs 31±7 mm vs 30±6 mm; p NS, respectivamente. Foram observados hipertrofia ventricular direita somente nos grupos DPOC (8±2 mm e 9±3 mm vs 5±1 mm; p<0,01), percentual de espessamento sistólico da parede lateral do ventrículo direito similar ( por centoRVLWT) (86±82 por cento vs 41±35 por cento vs 86±89 por cento; p NS) e diferentes frações de ejeção ventricular esquerda entre os 3 grupos (69±9 por cento vs 55±16 por cento vs 76±6 por cento; p<0,01); correlação linear positiva e significante entre o diâmetro diastólico do ventrículo esquerdo (VE) e o débito sistólico do VE (r=0,72, p < 0,01). Não houve correlação entre os volumes pulmonares e a gasometria arterial com a função ventricular. CONCLUSAO: Não houve correlação entre a gravidade da função pulmonar e o grau de comprometimento da função ventricular. Fica a ser elucidado se um preservado por centoRVLWT significa a possibilidade de reversibilidade da função ventricular direita. No entanto, confirmamos a presença do fenômeno da interdependência ventricular.

Estenose valvar aórtica: influência do sexo sobre a geometria e funçäo ventricular esquerda em pacientes abaixo de 70 anos / Aortic stenosis: gender influence on left ventricular geometry and function in patients under 70 years of age

Objetivo - Verificar-se as características adaptativas do ventrículo esquerdo (VE), também, estão presentes em indivíduos < 70 anos, com estenose valvar aórtica grave (EA). Métodos - Estudamos 40 pacientes consecutivos,<70 anos de idade, com EA, sem doença arterial coronariana, encaminhados à cirurgia, sendo 22 homens e 18 mulheres, (idade de 49,8+14,3 anos). Foram coligidos os sintomas cardíacos, presença de hipertensão arterial sistêmica (HAS), classe funcional de acordo com a NYHA e a etiologia do EA. Ao Dopplerecocardiograma foram estudados as dimensões cavitárias, a fração de ejeção (FE) e fração de encurtamento cavitário (FEC), massa (MS) e espessura diastólica relativa (EDR) do VE. Resultados - Quatorze homens e 11 mulheres estavam em CF III/IV (p=0,70). A freqüência de sintomas foi igual em ambos os sexos. Havia mais mulheres com HAS do que nos homens (10 contra 2, p=0,0044). As mulheres apresentaram menor índice de diâmetro diastólico final do VE (32,1+6,5 x 36,5+5,3 mm/m2, p=0,027), de diâmetro sistólico final (19,9+5,9 x 26,5+6,4mm/m2, p=0,0022) e MS (211,4+71,1 x 270,9+74,9g/m2, p=0,017) A FE (66,2+13,4 x 52,0+14,6 por cento, p=0,0032), FEC (37,6+10,7 x 27,9+9,6 por cento, p=0,0046) e EDR (0,58+0,22 x 0,44+0,09), p=0,0095) eram significativamente maiores nas mulheres. Conclusão - É o sexo e não a idade dos pacientes que influi na resposta adaptativa do VE à EA.

Melhora da disfunçäo ventricular esquerda após a correçäo cirúrgica da insuficiência mitral crônica grave / Improvement in left ventricular dysfunction after surgical correction of mitral regurgitation

OBJECTIVE: To evaluate whether left ventricular end-systolic (ESD) diameters £ 51mm in patients (pt) with severe chronic mitral regurgitation (MR) are predictors of a poor prognosis after mitral valve surgery (MVS). METHODS: Eleven pt (aged 36±13 years) were studied in the preoperative period (pre), median of 36 days; in the early postoperative period (post1), median of 9 days; and in the late postoperative period (post2), mean of 38.5±37.6 months. Clinical and echocardiographic data were gathered from each pt with MR and systolic diameter 51mm (mean = 57±4mm) to evaluate the result of MVS. Ten patients were in NYHA Class III/IV. RESULTS: All but 2 pt improved in functional class. Two pt died from heart failure and infectious endocarditis 14 and 11 months, respectively, after valve replacement. According to ejection fraction (EF) in post2, we identified 2 groups: group 1 (n=6), whose EF decreased in post1, but increased in post2 (p=0.01) and group 2 (n=5), whose EF decreased progressively from post1 to post2 (p=0.10). All pt with symptoms lasting £ 48 months had improvement in EF in post2 (p=0.01). CONCLUSION: ESD 51mm are not always associated with a poor prognosis after MVS in patients with MR. Symptoms lasting up to 48 months are associated with improvement in left ventricular function

A identificaçäo cinecoronariográfica da lesäo do tronco da coronária esquerda é indicaçäo de cirurgia de revascularizaçäo de emergência ou urgência? / Is the identification of a lesion in the left main coronary artery an indication for an emergent or urgent coronary artery bypass surgery?

OBJETIVO: Esse estudo tem por objetivo verificar se a identificaçäo da lesäo do tronco da coronária esquerda (LTCE) igual ou superior à 50 'por cento' coloca seus portadores em risco aumentado de eventos coronarianos e justifica a indicaçäo de cirurgia dentro de 30 dias da identificiaçäo da lesäo. MÉTODOS: Entre novembro de 1993 a agosto de 1996 nós selecionamos todos os pacientes com LTCE e indicaçäo de cirurgia de revascularizaçäo. Nós estudamos o grau de obstruçäo da LTCE, dominância arterial, diâmetros cavitários e fraçäo de encurtamento ventriculr esquerdo ao ecocardiograma bidimensional, o motivo da indicaçäo de coronariografia, o intervalo de tempo entre a coronariografia e a cirurgia de revascularizaçäo e os eventos coronários (insuficiência aguda, arritmia ventricular complexa, infarto agudo do miocárdio, necessidade de cirurgia de emergência ou urgência ou morte cardíaca). Os pacientes foram dividididos em dois grupos de acordo com a indicaçäo de coronariografia: grupo 1, composto por 7 pacientes com angina instável e grupo 2, composto por 49 pacientes com doença isquêmica estável. RESULTADOS: Havia maior número de fumantes (p=0,03) no grupo 1. Näo houve diferença nas dimensöes cavitárias ou na fraçäo de encurtamento ventricular....CONCLUSÄO: Com exceçäo dos pacientes com angina instável, o diagnóstico da LTCE acima de 50 'por cento' näo indica necessidade imediata de cirurgia de revascularizaçäo miocárdica.