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2.
Rev Port Cir Cardiotorac Vasc ; 26(2): 147-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476817

RESUMO

We report the case of a 44 year-old patient with complex ACHD, admitted with acute decompensated heart failure (ADHF) in hemodynamic profile B. He had a single ventricle with pulmonary atresia, previously submitted to three modified Blalock-Taussig shunts (mBTs) at the age of 2, 12 and 19 years old. Despite conventional treatment with diuretics, ß-blockers (BB) and isosorbide dinitrate the patient progressed to profile C and the transthoracic echocardiogram disclosed a reduced systolic function. Likewise, levosimendan was commenced and an appropriate decongestion and a marked reduction in the NT-proBNP were seen. Treatment with angiotensin-converting-enzyme inhibitor, BB, ivabradine and mineralocorticoid receptor was optimized. The patient was discharged home after 26 days in NYHA class III and referred for heart transplant after right heart catheterization. To our knowledge, this is the first report of successful levosimendan's use in ADHF in a mBTs long-term survivor.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/tratamento farmacológico , Ventrículos do Coração/anormalidades , Simendana/uso terapêutico , Adulto , Procedimento de Blalock-Taussig , Cardiopatias Congênitas/complicações , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Artéria Pulmonar/anormalidades , Artéria Pulmonar/cirurgia , Resultado do Tratamento
3.
Rev Assoc Med Bras (1992) ; 65(4): 524-529, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31066804

RESUMO

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Assuntos
Cardiomiopatia Dilatada/tratamento farmacológico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Simendana/uso terapêutico , Brasil , Cardiomiopatia Dilatada/mortalidade , Tomada de Decisão Clínica , Insuficiência Cardíaca/mortalidade , Humanos , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento
4.
Int J Pediatr Otorhinolaryngol ; 122: 70-75, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30978472

RESUMO

OBJECTIVES: Cisplatin is employed for chemotherapeutic purposes in several types of adult and pediatric cancer. However, side-effects including nephrotoxicity, ototoxicity, gastrointestinal effects and neuropathy restrict the use of the drug due to their adverse impacts on quality of life. This study aimed to determine whether levosimendan exhibits a protective effect against cisplatin-related ototoxicity in a rat model by means of functional, biochemical and histochemical analysis. METHODS: The study was employed with 24 female Sprague Dawley rats. After distortion product otoacoustic emissions (DPOAE) tests applied to all rats, rats were randomly assigned into four groups of six animals each. A single intraperitoneal 15 mg/kg dose of cisplatin was administered to Cisplatin group. Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days. Cisplatin + Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day of the study. Control group received 8 mL/kg/day intraperitoneal saline solution for five consecutive days. The DPOAE test was repeated on the 6th day of the study. All rats were then sacrificed, the cochleas were removed and set aside for biochemical and histopathological analyses. RESULTS: A significant increase in levels of Malondialdehyde (MDA) and significantly lower activities of superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were observed at rats of cisplatin group. Administration of levosimendan showed significantly lower cochlear MDA levels, while SOD and GPx activities both increased significantly. The DPOAE test performed at 6th day of the study showed a significant impairment in the signal-noise ratio (SNR) levels of rats in Cisplatin group. The SNR levels of rats treated with levosimendan were significantly higher than those of cisplatin group and were similar to those of the control group. Cisplatin impaired the cochlear structure and a severe Caspase 3 and 8-hydroxy-2' -deoxyguanosine (8-OHdG) immunopositivity was observed at cochlea of the rats of cisplatin group. Administration of levosimendan protected the structure of cochlea and there was a mild Caspase 3 and 8OHdG immunopositivity. CONCLUSION: Our data demonstrate that levosimendan protects hearing against cisplatin-induced ototoxicity and obviates cellular degeneration. It also significantly reduces oxidative stress and apoptosis, probable mechanisms involved in ototoxicity.


Assuntos
Cóclea/metabolismo , Cóclea/patologia , Perda Auditiva/prevenção & controle , Inibidores da Fosfodiesterase 3/uso terapêutico , Simendana/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Cisplatino/efeitos adversos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/metabolismo , Audição/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Perda Auditiva/fisiopatologia , Malondialdeído/metabolismo , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Razão Sinal-Ruído , Superóxido Dismutase/metabolismo
5.
Curr Mol Pharmacol ; 12(2): 160-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30848225

RESUMO

BACKGROUND AND OBJECTIVE: Levosimendan is a positive inotropic and a vasodilator agent with pleotropic characteristics that include antioxidation, anti-inflammation and smooth muscle vasodilation. METHODS: In this study, the effects of levosimendan (0, 0.1, 1, 10, and 20 µg/ml) on oxidative DNA damage and sister-chromatid exchanges (SCEs) were evaluated in human cultured lymphocytes. RESULTS: The results showed that levosimendan increased the frequency of SCEs in all examined concentrations (P<0.01) except for 0.1 µg/ml. On the other hand, levosimendan did not induce oxidative DNA damage as measured by the 8-OHdG biomarker (P > 0.05). In addition, neither mitotic arrest nor proliferation index was affected by levosimendan at all examined doses (P > 0.05). CONCLUSION: In conclusion, levosimendan might be associated with increases in sister-chromatid exchanges in cultured human lymphocytes. In vivo studies are required to confirm the present findings.


Assuntos
Dano ao DNA/efeitos dos fármacos , Simendana/farmacologia , Biomarcadores/análise , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Mitose/efeitos dos fármacos , Troca de Cromátide Irmã/efeitos dos fármacos
6.
Pediatr Cardiol ; 40(3): 668-670, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30796500

RESUMO

The longer survival of patients with Duchenne muscular dystrophy due to advances in clinical care has increased the incidence of Duchenne muscular dystrophy-associated cardiomyopathy, a nearly consistent feature in the third decade of life. A 26-year-old patient with Duchenne muscular dystrophy experienced severe acute heart failure triggered by pneumonia. Levosimendan was effective in improving heart function.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Distrofia Muscular de Duchenne/complicações , Simendana/uso terapêutico , Doença Aguda , Adulto , Cardiomiopatias/etiologia , Humanos , Ácido Láctico/sangue , Masculino , Peptídeo Natriurético Encefálico/sangue , Pneumonia/complicações
8.
J Clin Anesth ; 52: 37-47, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30172838

RESUMO

OBJECTIVES: Patients with preoperative low left ventricular ejection fraction (LVEF) are known to be associated with high morbidities and mortality in cardiac surgery. The primary aim of this review was to examine the clinical outcomes of levosimendan versus placebo in patients with preoperative low LVEF ≤ 50% undergoing cardiac surgery. DATA SOURCES: MEDLINE, EMBASE, PubMed and CENTRAL were searched systematically from their inception until June 2018. REVIEW METHODS: All the randomised clinical trials (RCTs) were included. RESULTS: Twelve trials were eligible (n = 1867) for inclusion in the data synthesis. In comparison to the placebo cohort, the levosimendan cohort showed a significant reduction in mortality (TSA = inconclusive; ρ = 0.002; I2 = 0%; FEM: OR 0.56; 95% CI 0.39, 0.80), especially in the subgroups of preoperative severe low LVEF ≤ 30% (ρ = 0.003; OR 0.33; 95% CI 0.16, 0.69), preoperative administering of levosimendan (ρ = 0.001; OR 0.46; 95% CI 0.29, 0.74) and patients who had bolus followed by infusion of levosimendan (ρ = 0.005; OR 0.50; 95% CI 0.30, 0.81). However, the effect on mortality was not significant in the subgroup analysis of high quality trials (ρ = 0.14; OR 0.73; 95% CI 0.47, 1.12). The levosimendan cohort showed a significantly lower incidence of low-cardiac-output-syndrome (ρ < 0.001; OR 0.58; 95% CI 0.46, 0.74) and lesser need for mechanical support of cardiac assist devices (ρ = 0.02; OR 0.39; 95% CI 0.18, 0.86). CONCLUSIONS: Given the low level of evidence and inconclusive TSA, the results of this meta-analysis neither support nor oppose the use of levosimendan in cardiac patients with preoperative low LVEF ≤ 50%. Therefore, multi-centre, adequately powered, randomised controlled trials are warranted. PROSPERO REGISTRATION: CRD42017067572.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiotônicos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Simendana/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Humanos , Complicações Pós-Operatórias/fisiopatologia , Volume Sistólico , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia
10.
Pharmacology ; 102(3-4): 138-141, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29982246

RESUMO

OBJECTIVES: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. METHODS: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. RESULTS: Infusion of levosimendan led to a reduction of aAPD90 (-9 ms, p < 0.05) and aERP (-13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). CONCLUSIONS: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP.


Assuntos
Antiarrítmicos/farmacologia , Fibrilação Atrial/induzido quimicamente , Hidrazonas/toxicidade , Piridazinas/toxicidade , Ranolazina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Fibrilação Atrial/prevenção & controle , Interações de Medicamentos , Hidrazonas/antagonistas & inibidores , Piridazinas/antagonistas & inibidores , Coelhos , Período Refratário Eletrofisiológico/efeitos dos fármacos , Simendana
11.
Drug Des Devel Ther ; 12: 1347-1352, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29861626

RESUMO

Aim: The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ) on lung injury after myocardial ischemia/reperfusion (I/R). Materials and methods: Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group), left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 µg/kg) (IRL) group, and I/R-thymoquinone (0.2 mL/kg) (IRTQ) group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies. Results: Increased expression of p53 and Bax was observed (4+), especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+). H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to be at an (1+, 2+) intensity that was usually weak and diffuse in multiple areas. Bcl 2 was not found to be expressed in any of the tissues. H&E staining revealed that that the lungs were severely damaged in the I/R group, with the walls of the channels and alveoli thickened and edematous, and also an intense inflammatory cell migration was observed. Immunohistochemical staining was more prominent in inflammatory areas and structures around the terminal bronchioles. Conclusion: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ. We suggest that findings of this study be elucidated with further large-scale clinical studies.


Assuntos
Benzoquinonas/uso terapêutico , Hidrazonas/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Piridazinas/uso terapêutico , Animais , Benzoquinonas/administração & dosagem , Hidrazonas/administração & dosagem , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Piridazinas/administração & dosagem , Ratos , Ratos Wistar , Simendana , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/biossíntese
12.
Zhonghua Nei Ke Za Zhi ; 57(6): 423-428, 2018 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-29925127

RESUMO

Objective: To investigate the effect of levosimendan on cardiac function and prognosis in elderly patients with septic myocardial contractility impairment. Methods: A prospective, randomized, controlled study was conducted. The elderly patients with septic myocardial contractility impairment who were admitted to Intensive Care Unit in Zhejiang Hospital were consecutively enrolled from January 2017 to September 2017. The key inclusive criterion was left ventricular ejection fraction (LVEF) ≤50% after fluid resuscitation. A total of 30 patients were randomly assigned to levosimendan group (n=15) and dobutamine group (n=15). Based onconventional treatment, intravenous dobutamine (5 µg per kilogram of body weight per minute) or levosimendan (0.2 µg per kilogram of body weight per minute)were continuously administrated for 24 hours in two groups. At 0 h,24 h,48 h, 72 h after injection, the following parameters or values were recorded including serum lactic acid (Lac), and echocardiographic parameters such as LVEF, stroke volume (SV). The time of mechanical ventilation, length of stay in ICU and 28-day mortality were compared in two groups. Results: Compared with dobutamine group, blood Lac at 24 h [(1.97±1.10)mmol/L vs. (2.73±2.06) mmol/L, P=0.002] decreased significantlyin levosimendan group. LVEF and SV were significantly higher in levosimendan group at 24 h [LVEF:(47.93±5.01)% vs.(45.60±5.47)%, P=0.004;SV:(47.73±14.01) ml vs. (44.80±16.89) ml, P=0.035;respectively], 48 h [LVEF:(51.07±5.05)% vs.(46.73±6.34)%, P=0.004;SV: (49.87±14.15) ml vs. (45.07±16.94) ml, P=0.005;respectively] and 72 h [LVEF:(53.20±5.92)% vs. (47.70±6.71)%, P=0.002;SV:(51.27±14.98) ml vs. (45.73±17.34) ml, P=0.010]. The time of mechanical ventilation, length of stay in ICU and 28-day mortality were comparable between two groups (P>0.05). Conclusions: Levosimendan improves cardiac systolic function and tissue perfusion in elderly patients with septic myocardial contractility impairment. However, cardiac diastolic function, liver and kidney function are not further improved by levosimendan compare with dubutamine. Time of mechanical ventilation, length of stay in ICU and 28-day mortality in two groups are similar.


Assuntos
Hidratação , Hidrazonas/farmacologia , Miocárdio/patologia , Piridazinas/farmacologia , Choque Séptico/tratamento farmacológico , Idoso , Biomarcadores/sangue , Ecocardiografia , Insuficiência Cardíaca , Humanos , Hidrazonas/uso terapêutico , Unidades de Terapia Intensiva , Ácido Láctico/sangue , Prognóstico , Estudos Prospectivos , Piridazinas/uso terapêutico , Respiração Artificial , Choque Séptico/sangue , Choque Séptico/fisiopatologia , Simendana , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
13.
Drug Des Devel Ther ; 12: 1777-1783, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950812

RESUMO

Despite the progress in the management of cerebral arterial aneurysms, subarachnoid hemorrhage (SAH) remains the major cause of neurological disability. While SAH-related deaths usually occur as a result of brain impairment due to hemorrhage, permanent neurological deficits are caused by cerebral ischemia due to edema and spasm of cerebral arteries. Additionally, ~20%-30% of patients with SAH develop secondary cardiomyopathy; this phenomenon is known as neurogenic stress cardiomyopathy (NSC), which is associated with increased mortality and poor long-term prognosis. Levosimendan is a new inotropic drug that causes calcium sensitization of troponin C, thus increasing contraction force of myofilaments. The drug also causes opening of ATP-dependent potassium channels in vascular smooth muscles, which results in dilatation of veins and arteries, including cerebral arteries. To date, there have been several reports of levosimendan application in patients with SAH and neurogenic stress cardiomyopathy, and the effect of the drug on vasospasm has been previously advocated. This paper presents a case report of a 57-year-old patient with massive SAH, where levosimendan was used for reducing vasospasm.


Assuntos
Artérias Cerebrais/efeitos dos fármacos , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/tratamento farmacológico , Angiografia Cerebral/métodos , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiopatologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Hidrazonas/efeitos adversos , Pessoa de Meia-Idade , Piridazinas/efeitos adversos , Simendana , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/fisiopatologia , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/fisiopatologia
14.
Biomed Res Int ; 2018: 7563083, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854789

RESUMO

Background: Recent studies suggest that levosimendan does not provide mortality benefit in patients with low cardiac output syndrome undergoing cardiac surgery. These results conflict with previous findings. The aim of the current study is to assess whether levosimendan reduces postoperative mortality in patients with impaired left ventricular function (mean EF ≤ 40%) undergoing cardiac surgery. Methods: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library Database through November 20, 2017. Inclusion criteria were random allocation to treatment with at least one group receiving levosimendan and another group receiving placebo or other treatments and cardiac surgery patients with a left ventricular ejection fraction of 40% or less. The primary endpoint was postoperative mortality. Secondary outcomes were cardiac index, pulmonary capillary wedge pressure (PCWP), length of intensive care unit (ICU) stay, postoperative atrial fibrillation, and postoperative renal replacement therapy. We performed trial sequential analysis (TSA) to evaluate the reliability of the primary endpoint. Results: Data from 2,152 patients in 15 randomized clinical trials were analyzed. Pooled results demonstrated a reduction in postoperative mortality in the levosimendan group [RR = 0.53, 95% CI (0.38-0.73), I2 = 0]. However, the result of TSA showed that the conclusion may be a false positive. Secondary outcomes demonstrated that PCWP, postoperative renal replacement therapy, and length of ICU stay were significantly reduced. Cardiac index was greater in the levosimendan group. No difference was found in the rate of postoperative atrial fibrillation. Conclusions: Levosimendan reduces the rate of death and other adverse outcomes in patients with low ejection fraction who were undergoing cardiac surgery, but results remain inconclusive. More large-volume randomized clinical trials (RCTs) are warranted.


Assuntos
Cardiotônicos/uso terapêutico , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Baixo Débito Cardíaco/tratamento farmacológico , Baixo Débito Cardíaco/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Humanos , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Substituição Renal , Simendana , Disfunção Ventricular Esquerda/cirurgia
15.
Orv Hetil ; 159(22): 870-877, 2018 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-29806474

RESUMO

Low output syndrome significantly increases morbidity and mortality of cardiac surgery and lengthens the durations of intensive care unit and hospital stays. Its treatment by catecholamines can lead to undesirable systemic and cardiac complications. Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (IK,ATP) opener agent. Due to these effects, it improves myocardium performance, does not influence adversely the balance between O2 supply and demand, and possesses cardioprotective and organ protective properties as well. Based on the scientific literature and experts' opinions, a European recommendation was published on the perioperative use of levosimendan in cardiac surgery in 2015. Along this line, and also taking into consideration cardiac surgeon, anaesthesiologist and cardiologist representatives of the seven Hungarian heart centres and the children heart centre, the Hungarian recommendation has been formulated that is based on two pillars: literature evidence and Hungarian expert opinions. The reviewed fields are: coronary and valvular surgery, assist device implantation, heart transplantation both in adult and pediatric cardiologic practice. Orv Hetil. 2018; 159(22): 870-877.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiotônicos/uso terapêutico , Hidrazonas/uso terapêutico , Cuidados Pré-Operatórios/métodos , Piridazinas/uso terapêutico , Doenças Cardiovasculares/cirurgia , Humanos , Hungria , Simendana
16.
J Card Surg ; 33(6): 322-329, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29785788

RESUMO

PURPOSE: We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large-scale randomized controlled trials (RCTs). METHODS: We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery. RESULTS: A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo-controlled randomized trials were included for meta-analysis. Pooled analysis showed that the all-cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55-1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68-1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66-1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94-3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22-1.02; P = 0.05). CONCLUSION: Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery.


Assuntos
Baixo Débito Cardíaco/mortalidade , Baixo Débito Cardíaco/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Bases de Dados Bibliográficas , Hidrazonas/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Piridazinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Simendana
17.
Ann Card Anaesth ; 21(2): 123-128, 2018 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29652271

RESUMO

Background: Off-pump coronary artery bypass surgery (OPCAB) is often complicated by hemodynamic instability, especially in patients with prior left ventricular (LV) dysfunction and appropriate choice of inotrope plays a vital role in perioperative management of these patients. Aim and Objective: To study hemodynamic effects and immediate outcome of prophylactic infusion of levosimendan in patients with the LV dysfunction undergoing OPCAB surgery and whether this strategy helps in successful conduct of OPCAB surgery. Materials and Methods: After Institutional Ethics Committee approval, 60 patients posted for elective OPCAB surgery were randomly divided into two groups (n = 30 each). Patients with the LV ejection fraction <30% were included. Study group was started on injection levosimendan (@ 0.1 µg/kg/min) in the previous night before surgery and continued for 24 h including intraoperative period. Hemodynamic monitoring included heart rate, invasive blood pressure, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), pulse oximetry, and arterial blood gases with serum lactates at as T0 (baseline), T1 (15 min after obtuse marginal and/or PDA anastomoses), T2 (at end of surgery), T3 (6 h after surgery in Intensive Care Unit [ICU]), T4 (12 h after surgery), and T5 (24 h after surgery in ICU). Vasopressor was added to maintain mean arterial pressure >60 mmHg. Chi-square/Fisher's exact/Mid P exact test and Student's t-tests were applied for categorical and continuous data. Results: CI was greater and PCWP reduced significantly in Group L during intraoperative and early postoperative period. Serum lactate concentration was lower in patients pretreated with levosimendan. Incidence of postoperative atrial fibrillation (POAF) (36.6 vs. 6.6%; P = 0.01), low cardiac output syndrome (LCOS) (30% vs. 6%; P = 0.02), and acute kidney injury (23.3% vs. 6.7%; P = 0.04) was less in Group L. Three patients (10%) in control group required conversion to cardiopulmonary bypass (CPB) as compared to none in the study group. There was no difference regarding ICU or hospital stay and mortality in both groups. Conclusion: Preoperative levosimendan helps in successful conduct of OPCAB and reduces the incidence of LCOS, POAF, conversion to CPB, and requirement of intra-aortic balloon pump.


Assuntos
Lesão Renal Aguda/prevenção & controle , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Vasoconstritores/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/cirurgia , Adulto , Idoso , Débito Cardíaco/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hidrazonas/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Pressão Propulsora Pulmonar , Piridazinas/administração & dosagem , Simendana , Vasoconstritores/administração & dosagem
18.
Eur J Pharmacol ; 829: 54-62, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29653089

RESUMO

This study aimed to determine the effects of levosimendan, a calcium sensitizer, on atrial contractility and atrial natriuretic peptide (ANP) secretion and its modification in hypertrophied atria. Isolated perfused beating rat atria were used from control and isoproterenol-treated rats. Levosimendan and its metabolite OR-1896 caused a positive inotropic effect and suppressed ANP secretion in rat atria. Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4 inhibitor also suppressed ANP secretion. Suppression of ANP secretion by 1 µM levosimendan was abolished by PDE3 inhibitor, but reversed by PDE4 inhibitor. Levosimendan-induced suppression of ANP secretion was potentiated by KATP channel blocker, but blocked by KATP channel opener. Levosimendan alone did not significantly change cyclic adenosine monophosphate (cAMP) efflux in the perfusate; however, levosimendan combined with PDE4 inhibitor markedly increased this efflux. The stimulation of ANP secretion induced by levosimendan combined with PDE4 inhibitor was blocked by the protein kinase A (PKA) inhibitor. In isoproterenol-treated atria, levosimendan augmented the positive inotropic effect and ANP secretion in response to an increased extracellular calcium concentration ([Ca+]o). These results suggests that levosimendan suppresses ANP secretion by both inhibiting PDE3 and opening KATP channels and that levosimendan combined with PDE4 inhibitor stimulates ANP secretion by activating the cAMP-PKA pathway. Modification of the effects of levosimendan on [Ca+]o-induced positive inotropic effects and ANP secretion in isoproterenol-treated rat atria might be related to a disturbance in calcium metabolism.


Assuntos
Fator Natriurético Atrial/metabolismo , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Hidrazonas/farmacologia , Piridazinas/farmacologia , Animais , Função Atrial/efeitos dos fármacos , Pressão Atrial/efeitos dos fármacos , Cálcio/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Átrios do Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertrofia/metabolismo , Hipertrofia/patologia , Hipertrofia/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Simendana
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