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1.
J Stroke Cerebrovasc Dis ; 29(2): 104509, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759913

RESUMO

BACKGROUND: There is ambiguity regarding the role of left ventricle wall motion abnormalities (LVWMAs) as a potential cardioembolic source in patients, who satisfy embolic stroke of undetermined source (ESUS) criteria. METHODS AND RESULTS: We analyzed prospectively collected data in 345 acute stroke patients, 185 (53.6%) stroke with atrial fibrillation (SwAF), and 160 (46.4%) stroke with LVWMA. LVWMA were younger (P = .003), had significantly higher frequency of stroke risk factors and lower ejection fraction (P < .001). No significant difference was found between the stroke pattern in SwAF and LVWMA except focal cortical, cortical-subcortical lesions were more frequent in LVWMA (P = .002). Mean wall motion score index (WMSI) was 1.523 (range 1.05-2.71) without any correlation between the severity of WMSI and multiple strokes (P = .976). In subgroup analyses vertical basal WMSI (P = .030) and vertical mid cavity WMSI (P = .010) was significantly related to branch arterial stroke. LVWMA 94 (65%) patients were on antiplatelet/anticoagulation compared to 47 (52.4%) with atrial fibrillation (AF), with no significant difference in stroke recurrence during 4 years follow-up (P = .15). CONCLUSIONS: Patients with LVWMA who satisfy ESUS criteria, have stroke pattern on diffusion-weighted magnetic resonance imaging and risk of stroke recurrence similar to AF-related stroke despite being on appropriate antiplatelet medications. Further studies with anticoagulation therapy may be required in this group of patients to improve the high risk of recurrent stroke.


Assuntos
Fibrilação Atrial/complicações , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/etiologia , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
2.
N Engl J Med ; 381(21): 1995-2008, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31535829

RESUMO

BACKGROUND: In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS: In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS: Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/mortalidade , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Glucosídeos/efeitos adversos , Hemoglobina A Glicada/análise , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/tratamento farmacológico
3.
J Pak Med Assoc ; 69(9): 1372-1375, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511728

RESUMO

Myocardial calcification is a rare echocardiographic finding, which is often found in patients who have suffered from a myocardial infarction. Rarely, myocardial calcification may be present in individuals without a significant medical history. Until today, there has not been a published case report emphasising the relation between myocardial calcification and cocaine usage. Herein, we report a case of a young male with diffuse calcification of the left ventricular myocardium, who had an addiction to cocaine. This case highlights an uncommon etiology for myocardial calcification and it may lead to further studies about cardiotoxic effects of cocaine.


Assuntos
Calcinose/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/complicações , Traumatismos Abdominais/complicações , Traumatismos Abdominais/cirurgia , Adulto , Suporte Vital Cardíaco Avançado , Calcinose/complicações , Cardiomiopatias/complicações , Colectomia , Cocaína Crack , Ecocardiografia , Infecções por Escherichia coli , Humanos , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Choque Cardiogênico/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/tratamento farmacológico , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/cirurgia
4.
Int Heart J ; 60(5): 1123-1130, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484861

RESUMO

Tolvaptan, a vasopressin V2 receptor antagonist, is approved in Japan for the treatment of fluid retention in patients with heart failure (HF), and in the United States for hyponatremia. The efficacy and safety of tolvaptan in patients with HF with reduced ejection fraction (HFrEF) have been demonstrated previously. However, its efficacy in patients with HF having preserved (HFpEF) and mid-range (HFmrEF) ejection fraction (EF) remains uncertain. The present subgroup analysis from the post-marketing surveillance SMILE Study aims to explore the efficacy and safety of tolvaptan across the HF subgroups (HFrEF, HFpEF, and HFmrEF).Patients with HF accompanied by fluid retention who received tolvaptan were enrolled. Primary endpoints were: change in body weight, 24-hour urine volume, congestive symptoms, and safety over 14-day treatment. Of the 3,349 patients enrolled, left ventricular EF data were available for 1,741 patients; 45.7% had HFpEF. Tolvaptan treatment resulted in body weight reduction and increases in 24-hour urine volume across the 3 subgroups. Congestive symptoms significantly improved over the 14-day treatment in all subgroups. The frequency of adverse events (AEs) was comparable across the subgroups; thirst was the most common AE.Tolvaptan provides a safe and effective option for treating fluid retention in patients with HFpEF, as well as HFmrEF and HFrEF.


Assuntos
Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Vigilância de Produtos Comercializados/métodos , Volume Sistólico/efeitos dos fármacos , Tolvaptan/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Medição de Risco , Índice de Gravidade de Doença , Volume Sistólico/fisiologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico
5.
Int Immunopharmacol ; 75: 105782, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376623

RESUMO

Sepsis-induced myocardial dysfunction (SIMD) is a manifestation of severe sepsis and is the main cause of increased mortality in sepsis patients. Naringin (Nar) has been reported to possess various biological activities and pharmacological properties. Therefore, the present study was undertaken to evaluate whether Nar can protect rats from the effects of LPS-induced SIMD. SD Rats were pre-treated with Nar (50 and 100 mg/kg) for 7 days before administration of a single dose of LPS (10 mg/kg, i.p.) on the seventh day. We found that Nar treatment markedly improved the global strain and strain rate of longitudinal, circumference, and radial direction (GLS/GLSr, GCS/GCSr, GRS/GRSr) compared to the LPS group. The layer-specific strain decreased gradually from the endocardial layer to epicardial layer, and the most serious damage occurred in the endocardial layer. Moreover, Nar significantly decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and myocardial enzymes (CK, LDH, and AST) induced by LPS and attenuated the inflammation response. Finally, Nar also inhibited NF-κB nuclear translocation and the activity of iNOS in H9c2 cardiomyocytes by activating PI3K/AKT signaling pathway. These results suggest that naringin may possess novel therapeutic potential for protection against LPS-induced myocardial dysfunction.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Flavanonas/uso terapêutico , Sepse/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiotônicos/farmacologia , Linhagem Celular , Citocinas/genética , Flavanonas/farmacologia , Lipopolissacarídeos , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Sepse/complicações , Sepse/metabolismo , Sepse/fisiopatologia , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
6.
Eur J Pharmacol ; 859: 172519, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31271743

RESUMO

Juvenile Paget disease (JPD1), an autosomal-recessive disorder, is characterized by extremely rapid bone turnover due to osteoprotegerin deficiency. Its extra-skeletal manifestations, such as hypertension and heart failure, suggest a pathogenesis with shared skeletal and cardiovascular system components. In spite of this, the effects of anti-hypertensive drugs on bone morphometry remain unknown. We administered an angiotensin II type 1 receptor blocker, olmesartan (5 mg/kg/day) to 8-week-old male mice lacking the osteoprotegerin gene, with and without 1 µg/kg/min of angiotensin II infusion for 14 days. Olmesartan treatment decreased systolic blood pressure, and echocardiography showed increased left ventricular systolic contractility. Three-dimensional micro-computed tomography scans demonstrated that olmesartan treatment increased trabecular bone volume (sham, +176%; angiotensin II infusion, +335%), mineral density (sham, +150%; angiotensin II infusion, +313%), and trabecular number (sham, +407%; angiotensin II infusion, +622%) in the tibia. Olmesartan increased cortical mineral density (sham, +19%; angiotensin II infusion, +24%), decreased the cortical bone section area (sham, -16%; angiotensin II infusion, -18%), decreased thickness (sham, -18%; angiotensin II infusion, -31%), and decreased the lacunar area (sham, -41%; angiotensin II infusion, -27%) in the tibia. Similar trend was observed in the femur. Moreover, olmesartan decreased angiotensin II-induced increases in tartrate-resistant acid phosphatase concentrations in plasma, but it affected neither type I procollagen N-terminal propeptides, nor the receptor activator of nuclear factor kappa-B ligand. Our data suggest that blockade of the angiotensin II type 1 receptor improves bone vulnerability, and helps to maintain the heart's structural integrity in osteoprotegerin-deficient mice.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Densidade Óssea/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/fisiopatologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Hipertrofia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ligante RANK/sangue , Sístole/efeitos dos fármacos , Sístole/fisiologia , Fosfatase Ácida Resistente a Tartarato/sangue
7.
Eur J Pharmacol ; 859: 172488, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31233746

RESUMO

Cardiac arrhythmias are among the most important pathologies that lead to sudden death. The discovery of new therapeutic options against arrhythmias with low adverse effects is of paramount importance. Farnesol is found in essential oils with antioxidant, anti-inflammatory and cardioprotective properties. The aim of this work was to investigate the effects of farnesol on the contractile and electrophysiological properties in rat heart and evaluate its antiarrhythmic action. It was evaluated farnesol effects on the left ventricular developed pressure, ECG, potassium (Ik) and L-type Ca2+ currents (ICa,L), action potential, intracellular Ca2+ transient, Ca2+ sparks and waves and reactive oxygen species production. Antiarrhythmic activity of farnesol was determined in vivo and ex vivo. The results showed that 50 µM farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca2+ transient but reduced ICa,L. Farnesol reduced action potential duration at 90% repolarization. Notably, farnesol improved arrhythmia score and the incidence of the most severe arrhythmias. Farnesol attenuated the generation of reactive oxygen species, Ca2+ sparks and waves in isolated cardiomyocytes submitted to Ca2+ overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of ICa,L and IK along with a decrease of reactive oxygen species production and normalized Ca2+ sparks and waves.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Farneseno Álcool/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Farneseno Álcool/uso terapêutico , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Oxigênio/metabolismo , Potássio/metabolismo , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/tratamento farmacológico
8.
Lakartidningen ; 1162019 Mar 26.
Artigo em Sueco | MEDLINE | ID: mdl-31192396

RESUMO

Pulmonary hypertension is a common consequence of left heart disease, associated with poor prognosis. The pulmonary hypertension in left heart disease is initially caused by a passive congestion of the pulmonary circuit but may, if longstanding, result in endothelial dysfunction and excessive vasoconstriction. In some cases pulmonary vascular remodeling occur, further complicating the condition and worsening the prognosis. It has been debated whether these patients may benefit from pulmonary vasodilators presently used in pulmonary arterial hypertension. Several randomized controlled trials have been performed on this subject, the vast majority being negative. As maintenance therapy may be harmful, they should be avoided outside clinical trials.


Assuntos
Hipertensão Pulmonar , Vasodilatadores/efeitos adversos , Disfunção Ventricular Esquerda/complicações , Contraindicações de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Vasodilatadores/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
9.
Intern Med ; 58(17): 2539-2543, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118405

RESUMO

Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.


Assuntos
Edema/diagnóstico por imagem , Edema/fisiopatologia , Síndrome POEMS/diagnóstico por imagem , Síndrome POEMS/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Citocinas/sangue , Dexametasona/uso terapêutico , Quimioterapia Combinada , Edema/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Síndrome POEMS/sangue , Síndrome POEMS/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/sangue , Fatores de Crescimento do Endotélio Vascular/sangue , Disfunção Ventricular Esquerda/tratamento farmacológico
10.
Am J Cardiol ; 124(3): 367-372, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126539

RESUMO

Direct acting oral anticoagulants (DOACs) are increasingly used as off-label alternatives to vitamin K antagonists for the treatment of left ventricular (LV) thrombus. However, efficacy data is limited to small case series and one meta-analysis of case reports. We aimed to determine the efficacy and safety of DOACs in treatment of LV thrombus utilizing transthoracic echocardiography (TTE) and clinical outcomes. We identified 52 patients (mean age = 64 years, 71% men) treated with a DOAC for LV thrombus (n = 26 apixaban, n = 24 rivaroxaban, and n = 2 dabigatran). Thirty-five of the 52 patients had a follow-up TTE after DOAC initiation. The primary end point was defined as resolution of LV thrombus (in patients with a subsequent TTE), or death, major bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke, or peripheral embolization. An experienced echocardiographer (M.L.M.) reviewed all TTEs for presence or absence of LV thrombus without knowledge of time point or clinical data. Twenty-nine of the 35 (83%) patients who underwent follow-up TTE had resolution of LV thrombus, with a mean duration of 264 days. Of the total study population, there was 1 cardioembolic event (transient ischemic attack) 52 days after initiating DOAC, 3 gastrointestinal bleeds requiring transfusion, and 1 patient with epistaxis requiring transfusion. All patients with a hemorrhagic complication were receiving concomitant antiplatelet therapy. DOAC therapy appears promising for the treatment of LV thrombus. A larger, prospective study is warranted to confirm these results.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Trombose/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Dabigatrana/uso terapêutico , Ecocardiografia , Epistaxe/etiologia , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/uso terapêutico , Trombose/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem
11.
Cardiovasc Diabetol ; 18(1): 55, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039778

RESUMO

BACKGROUND: Liraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease. METHODS: Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported. RESULTS: 23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (- 56 mL/s (- 91 to - 21)), E/A ratio (- 0.17 (- 0.27 to - 0.06)), Edec (- 0.9 mL/s2 * 10-3 (- 1.3 to - 0.2)) and E/Ea (- 1.8 (- 3.0 to - 0.6)), without affecting A (3 mL/s (- 35 to 41)) and Ea (0.4 cm/s (- 0.9 to 1.4)). Liraglutide reduced stroke volume (- 9 mL (- 16 to - 2)) and ejection fraction (- 3% (- 6 to - 0.1)), but did not change cardiac output (- 0.4 L/min (- 0.9 to 0.2)), cardiac index (- 0.1 L/min/m2 (- 0.4 to 0.1)) and peak ejection rate (- 46 mL/s (- 95 to 3)). CONCLUSIONS: Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Liraglutida/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Países Baixos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
12.
PLoS One ; 14(4): e0215818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009519

RESUMO

This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with dilated cardiomyopathy (DCM), especially in relation to left ventricular (LV) dysfunction. Furthermore, transmission electron microscopy of the diseased tissue was carried out to investigate if the gene expression changes are translated into ultrastructural alterations. LV tissue samples from patients with DCM (n = 13) and from controls (CNT; n = 10) were analyzed by RNA-sequencing, whereupon the altered expression (P < 0.05) of 13 autophagy- and 3 phagocytosis-related genes was observed. The expression changes of the autophagy-related genes NRBP2 and CALCOCO2 were associated with cardiac dysfunction and remodeling (P < 0.05). The affected patients had a higher activity of these degradation processes, as evidenced by the greater number of autophagic structures in the DCM tissue (P < 0.001). Differences in the ultrastructural distribution were also found between the DCM and CNT tissues. These results show that in patients with DCM, the altered expression of NRBP2 and CALCOCO2 is related to LV dysfunction and remodeling. Clarification of the molecular mechanisms of cardiac autophagy would help in the future development of therapies to improve LV performance.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Relacionadas à Autofagia/genética , Cardiomiopatia Dilatada/genética , Proteínas Nucleares/genética , RNA Mensageiro/genética , Receptores Citoplasmáticos e Nucleares/genética , Disfunção Ventricular Esquerda/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Diuréticos/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Nucleares/metabolismo , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Análise de Sequência de RNA , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
13.
J Cardiovasc Med (Hagerstown) ; 20(5): 343-350, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30921270

RESUMO

AIMS: Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT). METHODS: DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6 ±â€Š3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24 h, at least 50 ventricular couplets/24 h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point. RESULTS: During a median follow-up of 152 months (interquartile range 100-234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47 ±â€Š7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36 ±â€Š12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039-1.179, P = 0.002 for 1 mm increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762-7.632, P = 0.001) emerged as predictors of SCD/MVAs during follow-up. CONCLUSION: A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.


Assuntos
Arritmias Cardíacas/epidemiologia , Cardiomiopatia Dilatada/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Volume Sistólico , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/mortalidade , Fármacos Cardiovasculares/uso terapêutico , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/mortalidade , Função Ventricular Esquerda/efeitos dos fármacos
14.
Chem Biol Interact ; 304: 186-193, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30885636

RESUMO

BACKGROUND: Adriamycin (ADR) is an effective antineoplastic drug; the clinical application of ADR is limited due to fatal heart dysfunction. Exenatide has antioxidant, anti-apoptotic and anti-inflammatory properties. It can alleviate heart damage induced by ischaemia-reperfusion injury. Thus, we assumed that exenatide would produce protective effects on ADR-induced heart dysfunction. METHOD: Mice were treated with exenatide 1 h prior to every ADR treatment for 20 days. Left ventricular function and performance were assessed by echocardiography. Additionally, H9c2 cells were pretreated with exenatide followed by ADR, and intracellular reactive oxygen species (ROS) and cell viability, as well as the lactate dehydrogenase (LDH) and the creatine kinase MB (CK-MB), were subsequently measured. Flow cytometry and TUNEL staining were applied to assess the effect of exenatide on cardiac damage caused by ADR. Western blot and RT-PCR were performed to detect the effect of exenatide on apoptosis-related genes (Bcl-2 and Bax) and inflammation-related genes and/or proteins (tumour necrosis factor-α, interleukin-6, nuclear factor-κB, and p53). RESULT: Echocardiography showed that cardiac dysfunction caused by ADR was significantly improved by treatment with exenatide. ADR mice had harmful changes in the levels of ROS and CK-MB/LDH production, as well as the targeted apoptotic and inflammatory molecules, and these effects were also reversed by exenatide. In vitro, exenatide mitigated ADR-induced oxidative stress and CK-MB/LDH production, as well as Annexin V+/PI+ and TUNEL+ apoptosis in H9c2 cells. CONCLUSION: In conclusion, our research demonstrated the potential protective effects of exenatide on ADR-induced heart dysfunction through suppressing oxidative stress, apoptosis and inflammation.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/antagonistas & inibidores , Exenatida/farmacologia , Hipoglicemiantes/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Doxorrubicina/farmacologia , Ecocardiografia , Exenatida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologia
15.
BMJ Case Rep ; 12(3)2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30852511

RESUMO

A previously healthy 44-year-old Caucasian man presented with recurrent syncope and was found to have a complete heart block with a ventricular rate of 24 bpm. No biochemical abnormalities were identified. Tick borne illnesses were ruled out. Paced echocardiogram revealed left ventricular systolic dysfunction with septal hypokinesis. Chest radiography and subsequent CT scan did not reveal adenopathy. However, a positron emission tomography scan demonstrated increased fluorodeoxyglucose uptake in the spleen, a right retro-clavicular lymph node, right ventricle and the interventricular septum of the heart. Excision biopsy of the retro-clavicular lymph node revealed non-caseating granulomas consistent with sarcoidosis. Complete heart block persisted despite steroid treatment. A pacemaker/biventricular implantable cardioverter defibrillator was placed for complete heart block and primary prevention of ventricular tachycardia and sudden cardiac death.


Assuntos
Bloqueio Cardíaco/diagnóstico , Sarcoidose/complicações , Baço/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Assistência ao Convalescente , Desfibriladores Implantáveis/provisão & distribução , Diagnóstico Diferencial , Ecocardiografia , Fluordesoxiglucose F18/metabolismo , Glucocorticoides/uso terapêutico , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/prevenção & controle , Bloqueio Cardíaco/terapia , Humanos , Linfonodos/patologia , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Doenças Raras , Sarcoidose/diagnóstico por imagem , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Baço/patologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/tratamento farmacológico
16.
Medicine (Baltimore) ; 98(8): e14657, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813209

RESUMO

Recent studies reported that high doses of short-acting loop diuretics are associated with poor outcomes in patients with heart failure (HF). Short-acting loop diuretics have been shown to activate the renin-angiotensin system (RAS) and have no favorable effects on cardiac sympathetic nervous system (SNS) activity. The goal of this study is to investigate the relationship between daily doses of furosemide and the outcomes of patients with left ventricular dysfunction (LVD) from the viewpoint of cardiac SNS abnormalities using iodine-123-labeled metaiodobenzylguanidine (l-MIBG) myocardial scintigraphy.We enrolled 137 hospitalized patients (62.5 ±â€Š14.2 years old, 103 men) with LVEF < 45% who underwent l-MIBG myocardial scintigraphy. A delayed heart-to-mediastinum ratio (delayed HMR) was assessed using l-MIBG scintigraphy. Cardiac events were defined as cardiac death or re-hospitalization due to the deterioration of HF. Cox proportional hazard analysis was used to identify predictors of cardiac events.Cardiac events occurred in 57 patients in a follow-up period of 33.1 ±â€Š30 months. In a multivariate Cox proportional hazard analysis, delayed HMR and furosemide doses were identified as independent predictors of cardiac events (P = .0042, P = .033, respectively). Inverse probability of treatment weighting Cox modeling showed that the use of furosemide (≥40 mg /day) was associated with cardiac events with a hazard ratio of 1.96 (P = .003). In the Kaplan-Mayer analysis, the cardiac event-free survival rate was significantly lower in patients treated with high doses of furosemide (≥60 mg/day vs 40-60 mg/day vs <40 mg/day, the Log-rank test P < .0001). In a receiver-operating characteristic (ROC) analysis, the cut-off value for cardiac events was 40 mg/day of furosemide. The cardiac event-free rate was significantly lower in patients with delayed HMR <1.8 (median value) and receiving furosemide ≥40 mg/day than in other patients (the Log-rank test P < .0001). Significant differences in cardiac event rates according to furosemide doses among patients with delayed HMR <1.8 were observed among patients without ß-blocker therapy (P = .001), but not among those with ß-blocker therapy (P = .127).The present results indicate that a relationship exists between higher doses of furosemide and poor outcomes. The prognosis of HF patients with severe cardiac SNS abnormalities receiving high-dose short-acting loop diuretics is poor.


Assuntos
Furosemida , Insuficiência Cardíaca , Coração , Sistema Nervoso Simpático/efeitos dos fármacos , Disfunção Ventricular Esquerda , 3-Iodobenzilguanidina/farmacologia , Idoso , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Feminino , Furosemida/administração & dosagem , Furosemida/efeitos adversos , Furosemida/farmacocinética , Coração/diagnóstico por imagem , Coração/inervação , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Compostos Radiofarmacêuticos/farmacologia , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico
17.
Breast Cancer Res Treat ; 175(3): 595-603, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30852761

RESUMO

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Receptor ErbB-2/metabolismo , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/metabolismo , Feminino , Humanos , Maitansina/administração & dosagem , Maitansina/efeitos adversos , Maitansina/análogos & derivados , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Estudos Prospectivos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia
18.
Int J Cardiovasc Imaging ; 35(7): 1309-1318, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30790116

RESUMO

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.


Assuntos
Função do Átrio Esquerdo , Remodelamento Atrial , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Função do Átrio Esquerdo/efeitos dos fármacos , Remodelamento Atrial/efeitos dos fármacos , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Meios de Contraste/administração & dosagem , Feminino , Fibrose , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
19.
Clin Sci (Lond) ; 133(3): 497-513, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30705107

RESUMO

An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during ischemia/reperfusion (I/R) injury. Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated. We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury. Forty male Wistar rats were subjected to a 30-min ischemia by coronary occlusion, followed by a 120-min reperfusion. The rats were then randomly divided into control and three treated groups: pre-ischemia, during-ischemia, and onset of reperfusion. A pharmacological mitochondrial fusion promoter-M1 (2 mg/kg) was used for intervention. Reduced mitochondrial fusion protein was observed after cardiac I/R injury. M1 administered prior to ischemia exerted the highest level of cardioprotection by improving both cardiac mitochondrial function and dynamics regulation, attenuating incidence of arrhythmia, reducing infarct size and cardiac apoptosis, which led to the preservation of cardiac function and decreased mortality. M1 given during ischemia and on the onset of reperfusion also exerted cardioprotection, but with a lower efficacy than when given at the pre-ischemia time-point. Attenuating a reduction in mitochondrial fusion proteins during myocardial ischemia and at the onset of reperfusion exerted cardioprotection by attenuating mitochondrial dysfunction and dynamic imbalance, thus reducing infarct size and improving cardiac function. These findings indicate that it could be a promising intervention with the potential to afford cardioprotection in the clinical setting of acute myocardial infarction.


Assuntos
Dinâmica Mitocondrial , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/administração & dosagem , Humanos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/metabolismo
20.
Eur J Pharmacol ; 847: 61-71, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30684466

RESUMO

Following myocardial infarction, the heart undergoes a series of dramatic compensations which may later form a maladaptive picture characterized by ventricular dilation and pump failure. Among several opioid agents, morphine has been shown to confer protection against reperfusion injury and infarct size. Here, we sought to study the cardioprotective effect of post-infarct morphine treatment against left ventricular adverse remodeling. We induced myocardial infarction in male Sprague - Dawley rats by ligating left anterior descending artery and then, treated these animals with three different doses of morphine -0.3, 3 and 10 mg/kg (i.p.). The echocardiographic evaluation depicted improved cardiac performance and lesser chamber dilation in the animals that had received 3 mg/kg of morphine. Next, we studied the effect of 3 mg/kg morphine administration on left ventricular hemodynamics, infarct size, tissue architecture, changes in lung and heart weight, circulating TNF-α level and post-MI mRNA expression of collagen-1, collagen-3, TGF-ß, TNF-α, MMP-2 and MMP-9. Five-day morphine administration markedly improved LV function, and also reduced infarct size, myocyte hypertrophy, fibrosis, index of infarct expansion, heart weight and serum TNF-α level. Moreover, morphine alleviated MI-induced increase in wet and dry lung weight. Morphine also altered the mRNA expression of fibrosis-related genes, TNF-α, MMP-2 and MMP-9. In conclusion, post-infarct morphine treatment can mitigate adverse remodeling and cardiac dysfunction after MI. Beside analgesic effect, we may be able to harvest benefits from the antifibrotic and anti-remodeling action of morphine in patients with the acute coronary syndrome.


Assuntos
Ventrículos do Coração/efeitos dos fármacos , Morfina/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Ecocardiografia/métodos , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Ventrículos do Coração/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Disfunção Ventricular Esquerda/metabolismo
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