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1.
Zentralbl Chir ; 148(3): 284-292, 2023 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-36167311

RESUMO

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque , Humanos , Sociedades Científicas , Circulação Extracorpórea , Sociedades Médicas , Alemanha
2.
Biomedicines ; 10(8)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36009478

RESUMO

BACKGROUND: In reverse-mode, cardiac sodium-calcium exchanger (NCX) can increase the cytoplasmic Ca2+ concentration in response to high intracellular Na+ levels, which may contribute to diastolic contractile dysfunction. Furthermore, increased spontaneous Ca2+ release from intracellular stores can activate forward mode NCX. The resulting transient inward current causes delayed afterdepolarization (DAD)-dependent arrhythmias. Moreover, recently, NCX has been associated with impaired relaxation and reduced cardiac function in heart failure with preserved ejection fraction (HFpEF). Since NCX is upregulated in human chronic atrial fibrillation (AF) as well as heart failure (HF), specific inhibition may have therapeutic potential. OBJECTIVE: We tested the antiarrhythmic, lusitropic and inotropic effects of a novel selective NCX-inhibitor (SAR296968) in human atrial myocardium. METHODS AND RESULTS: Right atrial appendage biopsies of 46 patients undergoing elective cardiac surgery in a predominant HFpEF cohort (n = 24/46) were investigated. In isolated human atrial cardiomyocytes, SAR296968 reduced the frequency of spontaneous SR Ca2+ release events and increased caffeine transient amplitude. In accordance, in isolated atrial trabeculae, SAR296968 enhanced the developed tension after a 30 s pause of electrical stimulation consistent with reduced diastolic sarcoplasmic reticulum (SR) Ca2+ leak. Moreover, compared to vehicle, SAR296968 decreased steady-state diastolic tension (at 1 Hz) without impairing developed systolic tension. Importantly, SAR296968 did not affect the safety parameters, such as resting membrane potential or action potential duration as measured by patch clamp. CONCLUSION: The novel selective NCX-inhibitor SAR296968 inhibits atrial pro-arrhythmic activity and improves diastolic and contractile function in human atrial myocardium, which may have therapeutic implications, especially for treatment of HFpEF.

3.
Unfallchirurgie (Heidelb) ; 125(7): 568-573, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34255104

RESUMO

A case of in-hospital thoracotomy with subsequent open chest cardiopulmonary resuscitation of a polytraumatized patient is reported. Emergency thoracotomies are rare interventions in challenging situations. Up to now there are only few standards or uniform education and training concepts. The indications are often a borderline decision. The aim of thoracotomy and open resuscitation in combination with a reduction in circulation, for example by cross-clamping the aorta, is to save time to address reversible causes of the hemorrhage, redirect the blood volume into the vital cerebral and coronary circulation and minimize bleeding from subdiaphragmatic bleeding sources. Ultimately, in case of doubt, the thoracotomy can be performed for the patient's benefit with the appropriate indications.


Assuntos
Reanimação Cardiopulmonar , Choque Hemorrágico , Aorta , Hemorragia/etiologia , Humanos , Choque Hemorrágico/etiologia , Toracotomia
4.
ESC Heart Fail ; 9(1): 506-518, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34811959

RESUMO

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque , Circulação Extracorpórea , Oxigenação por Membrana Extracorpórea/métodos , Alemanha , Humanos , Guias de Prática Clínica como Assunto , Choque/etiologia
6.
Anaesthesist ; 70(11): 942-950, 2021 11.
Artigo em Alemão | MEDLINE | ID: mdl-34665266

RESUMO

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque , Circulação Extracorpórea , Alemanha , Humanos , Sistemas de Manutenção da Vida
7.
Med Klin Intensivmed Notfmed ; 116(8): 678-686, 2021 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-34665281

RESUMO

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque , Circulação Extracorpórea , Alemanha , Humanos , Sistemas de Manutenção da Vida
9.
BMJ Open ; 11(7): e042857, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230011

RESUMO

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is performed in elderly patients with severe aortic valve stenosis and increased operative risks. We tested the hypothesis that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have a predictive value for prevalent complications after TAVI and could serve as indicators of systemic inflammation in the early postoperative period. DESIGN: Prospective observational study. SETTING: This study is a secondary analysis of multicentre CESARO- study. PARTICIPANTS: 48 patients with TAVI were included and 43 obtained the complete assessment. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients' clinical parameters, demographic data, peripheral AChE and BChE activities and routine blood markers were assessed throughout the perioperative period using bedside point-of-care measurements for AChE and BChE. Postoperative complication screening was conducted up to the third postoperative day and included infections, delirium and heart-rhythm disturbances. After assessment, the patients were divided into complication and noncomplication group. RESULTS: Of 43 patients, 24 developed postsurgical complications (55.8%). Preoperative assessment showed no significant differences regarding demographic data and laboratory markers, but preoperative BChE levels were significantly lower in patients who developed postoperative complications (complication group 2589.2±556.4 vs noncomplication group 3295.7±628.0, Cohen's r=0.514, p<0.001). In complication group, we observed an early, sustained reduction in BChE activity from preoperative to postoperative period. In complication group, BChE levels were significantly lower at each time point compared with noncomplication group. AChE activity showed no significant difference between both groups. Complication group also had longer stay in hospital overall. CONCLUSION: BChE could be a useful perioperative biomarker to identify patients with a higher risk for postoperative complications after TAVI. By using point-of-care measurements, the levels of BChE are fast available and can lead to an early targeted therapy. Predicting the length of the hospital stay might play an important role in staff and resource management for these patients. TRIAL REGISTRATION NUMBER: NCT01964274; Post-results.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso , Estenose da Valva Aórtica/cirurgia , Biomarcadores , Butirilcolinesterase , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
10.
J Cardiothorac Surg ; 16(1): 205, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321019

RESUMO

BACKGROUND: Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial. METHODS: We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of < 70 mmHg, a dose of norepinephrine ≥0.8 mg*h- 1 and a continuously increasing need for catecholamine, without ventricular dysfunction. RESULTS: We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine. CONCLUSIONS: CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Vasoplegia , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Humanos , Masculino , Azul de Metileno , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Vasoplegia/tratamento farmacológico , Vasoplegia/etiologia , Função Ventricular Esquerda
11.
PLoS One ; 16(2): e0246724, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571258

RESUMO

OBJECTIVES: Surgery for acute type A aortic dissection is associated with several perioperative complications, such as acute respiratory dysfunction (ARD). The aim of this study was to investigate perioperative risk factors involved in the development of ARD and whether antibiotic treatment has an impact. METHODS: 243 patients underwent surgery for acute type A aortic dissection between 2008 and 2017. The patients were retrospectively divided into the ARD and NON-ARD group. ARD was defined as PaO2/FiO2 ≤ 200 mmHg (PF ratio) within 48 hours after surgery. All patients received either narrow- or broad-spectrum antibiotics. RESULTS: After the exclusion of 42 patients, 201 patients were analyzed. The PF ratio of the ARD group was significantly lower than of the NON-ARD group within the first 7 days. ARD patients (n = 111) were significantly older (p = .031) and had a higher body mass index (BMI) (p = .017). ARD patients required longer postoperative ventilation (2493 vs. 4695 [min], p = .006) and spent more days in the intensive care unit (7.0 vs. 8.9 [days], p = .043) compared to NON-ARD. The mortality was significantly lower for ARD than for NON-ARD patients (p = .030). The incidence of pneumonia was independent of the antibiotic treatment regime (p = .391). Renal and neurological complication rate was higher in patients treated with broad-spectrum antibiotic. CONCLUSION: ARD is the main complication (55%) that occurs approximately 24 hours after surgery for acute type A aortic dissection. The preoperative risk factors for ARD were higher age and increased BMI. Patients on broad-spectrum antibiotics did not show an improved postoperative outcome compared to patients with narrow-spectrum antibiotics.


Assuntos
Antibacterianos/uso terapêutico , Dissecção Aórtica/cirurgia , Transtornos Respiratórios/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Transtornos Respiratórios/etiologia , Estudos Retrospectivos
12.
ESC Heart Fail ; 7(5): 2871-2883, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32691522

RESUMO

AIMS: Excessive activation of Ca/calmodulin-dependent kinase II (CaMKII) is of critical importance in heart failure (HF) and atrial fibrillation. Unfortunately, lack of selectivity, specificity, and bioavailability have slowed down development of inhibitors for clinical use. We investigated a novel CaMKIIδ/CaMKIIÉ£-selective, ATP-competitive, orally available CaMKII inhibitor (RA608) on right atrial biopsies of 119 patients undergoing heart surgery. Furthermore, we evaluated its oral efficacy to prevent deterioration of HF in mice after transverse aortic constriction (TAC). METHODS AND RESULTS: In human atrial cardiomyocytes and trabeculae, respectively, RA608 significantly reduced sarcoplasmic reticulum Ca leak, reduced diastolic tension, and increased sarcoplasmic reticulum Ca content. Patch-clamp recordings confirmed the safety of RA608 in human cardiomyocytes. C57BL6/J mice were subjected to TAC, and left ventricular function was monitored by echocardiography. Two weeks after TAC, RA608 was administered by oral gavage for 7 days. Oral RA608 treatment prevented deterioration of ejection fraction. At 3 weeks after TAC, ejection fraction was 46.1 ± 3.7% (RA608) vs. 34.9 ± 2.6% (vehicle), n = 9 vs. n = 12, P < 0.05, ANOVA, which correlated with significantly less CaMKII autophosphorylation at threonine 287. Moreover, a single oral dose significantly reduced inducibility of atrial and ventricular arrhythmias in CaMKIIδ transgenic mice 4 h after administration. Atrial fibrillation was induced in 6/6 mice for vehicle vs. 1/7 for RA608, P < 0.05, 'n - 1' χ2 test. Ventricular tachycardia was induced in 6/7 for vehicle vs. 2/7 for RA608, P < 0.05, 'n - 1' χ2 test. CONCLUSIONS: RA608 is the first orally administrable CaMKII inhibitor with potent efficacy in human myocytes. Moreover, oral administration potently inhibits arrhythmogenesis and attenuates HF development in mice in vivo.


Assuntos
Calmodulina , Insuficiência Cardíaca , Animais , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Humanos , Camundongos , Retículo Sarcoplasmático/metabolismo
13.
Front Med (Lausanne) ; 7: 599533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33392222

RESUMO

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.

14.
BMJ Open ; 9(4): e025825, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31048439

RESUMO

OBJECTIVES: This study was performed to analyse anaesthesia-related complications and side effects in patients undergoing transcatheter aortic valve implantation (TAVI) under general anaesthesia. DESIGN: Retrospective study. SETTING: The study was performed as a single-centre study in a hospital of tertiary care in Germany. PARTICIPANTS: All 853 patients, who underwent TAVI at the Universitätsklinikum Regensburg between January 2009 and July 2015, were included. 52.5% were female patients. PRIMARY AND SECONDARY OUTCOME MEASURES: We gathered information, such as recent illness, vital parameters and medication administered during the intervention and postoperatively for 12 hours. We analysed all anaesthesia-related complications and anaesthesia-related side effects that occurred during the intervention and entire hospital stay. RESULTS: We analysed all 853 TAVI procedures. The mean patient age was 79 ± 6 years. In 99.5% of cases, we used volatile-based anaesthesia. 2.8% (n=24; transfemoral (TF): n=19 [3.8%]; transapical (TA): n=5 [1.4%]) of all cases suffered from anaesthesia-related complications. 819 (TF: n=447; TA: n=372) anaesthesia-related side effects occurred in 586 (68.7%, TF: n=325 [64.2%], TA: n=261 [75.2%]) patients. Neither the complications nor the side effects had any serious consequences. Intraoperative hypothermia in 44% of cases (TF: n=202 [39.9%]; TA: n=173 [49.9%]) and postoperative nausea and vomiting in 27% (n=232; TF: n=131 [25.9%], TA: n=101 [29.1%]) of cases were the most common anaesthesia-related side effects. CONCLUSION: In this study, serious anaesthesia-related complications were rarely seen, and non-critical anaesthesia-related side effects could have been avoided through consistent prophylaxis and management. Therefore, despite their high anaesthetic risk, general anaesthesia is justifiable in patients who underwent TAVI.


Assuntos
Anestesia Geral/efeitos adversos , Complicações Intraoperatórias/etiologia , Complicações Pós-Operatórias/etiologia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Estudos Retrospectivos
15.
Mediators Inflamm ; 2019: 8274903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804708

RESUMO

INTRODUCTION: Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions. METHODS: Sham surgery or CLP was performed in male Wistar rats (n = 60). Animals were randomized into four groups: physostigmine, 100 µg/kg; neostigmine, 75 µg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry at t = 0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined. RESULTS: CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals at t > 6 h, AChE activity did not change in the sham group. BChE activity decreased at t > 20 h in the control animals. CONCLUSION: While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.


Assuntos
Acetilcolinesterase/metabolismo , Biomarcadores/metabolismo , Butirilcolinesterase/metabolismo , Neostigmina/uso terapêutico , Neutrófilos/efeitos dos fármacos , Fisostigmina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Animais , Gasometria , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
16.
ESC Heart Fail ; 5(4): 642-648, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30117720

RESUMO

AIMS: The EMPA-REG OUTCOME study showed reduced mortality and hospitalization due to heart failure (HF) in diabetic patients treated with empagliflozin. Overexpression and Ca2+ -dependent activation of Ca2+ /calmodulin-dependent kinase II (CaMKII) are hallmarks of HF, leading to contractile dysfunction and arrhythmias. We tested whether empagliflozin reduces CaMKII- activity and improves Ca2+ -handling in human and murine ventricular myocytes. METHODS AND RESULTS: Myocytes from wild-type mice, mice with transverse aortic constriction (TAC) as a model of HF, and human failing ventricular myocytes were exposed to empagliflozin (1 µmol/L) or vehicle. CaMKII activity was assessed by CaMKII-histone deacetylase pulldown assay. Ca2+ spark frequency (CaSpF) as a measure of sarcoplasmic reticulum (SR) Ca2+ leak was investigated by confocal microscopy. [Na+ ]i was measured using Na+ /Ca2+ -exchanger (NCX) currents (whole-cell patch clamp). Compared with vehicle, 24 h empagliflozin exposure of murine myocytes reduced CaMKII activity (1.6 ± 0.7 vs. 4.2 ± 0.9, P < 0.05, n = 10 mice), and also CaMKII-dependent ryanodine receptor phosphorylation (0.8 ± 0.1 vs. 1.0 ± 0.1, P < 0.05, n = 11 mice), with similar results upon TAC. In murine myocytes, empagliflozin reduced CaSpF (TAC: 1.7 ± 0.3 vs. 2.5 ± 0.4 1/100 µm-1  s-1 , P < 0.05, n = 4 mice) but increased SR Ca2+ load and Ca2+ transient amplitude. Importantly, empagliflozin also significantly reduced CaSpF in human failing ventricular myocytes (1 ± 0.2 vs. 3.3 ± 0.9, P < 0.05, n = 4 patients), while Ca2+ transient amplitude was increased (F/F0 : 0.53 ± 0.05 vs. 0.36 ± 0.02, P < 0.05, n = 3 patients). In contrast, 30 min exposure with empagliflozin did not affect CaMKII activity nor Ca2+ -handling but significantly reduced [Na+ ]i . CONCLUSIONS: We show for the first time that empagliflozin reduces CaMKII activity and CaMKII-dependent SR Ca2+ leak. Reduced Ca2+ leak and improved Ca2+ transients may contribute to the beneficial effects of empagliflozin in HF.


Assuntos
Compostos Benzidrílicos/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Glucosídeos/farmacologia , Ventrículos do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Western Blotting , Sinalização do Cálcio , Células Cultivadas , Modelos Animais de Doenças , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
17.
Clin Res Cardiol ; 107(12): 1148-1159, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29943269

RESUMO

BACKGROUND: Sleep-disordered breathing (SDB) may increase the risk of postoperative complications in patients after cardiac surgery. This study evaluated the length of hospital stay as well as postoperative cardiac, respiratory, and renal complications after elective coronary artery bypass grafting (CABG) in patients without SDB, with central sleep apnea (CSA), or with obstructive sleep apnea (OSA). METHODS: The presence and type of SDB had been assessed with polygraphic recordings in 100 patients the night before elective CABG surgery. SDB was defined as an apnea-hypopnea index (AHI) of ≥ 15/h. Prolonged length of hospital stay (LOS) and postoperative hemodynamic instability due to any cause were retrospectively evaluated as primary endpoints and cardiac, respiratory, and renal complications as secondary endpoints. RESULTS: 37% of patients had SDB, 14% CSA, and 23% OSA. LOS differed significantly between patients without SDB and those with CSA and OSA [median (25;75. percentile): 8.0 days (7.5;11.0) vs. 9.5 days (7.0;12.5) vs. 12.0 days (9.0;17.0), Kruskal-Wallis test between three groups: p = 0.023; OSA vs. no SDB: p = 0.005]. AHI was significantly associated with prolonged LOS [> 9 days; odds ratio (OR) (95% confidence interval): 1.047 (1.001;1.095), p = 0.044]. Prolonged need of vasopressors (≥ 48 h) was observed in 36% of patients without SDB, in 64% with CSA, and in 62% with OSA (p = 0.037). AHI was significantly associated with prolonged (≥ 48 h) need of vasopressors [OR (95% CI): 1.052 (1.002;1.104), p = 0.040], independent of any confounders. CONCLUSIONS: SDB, particularly OSA, is associated with prolonged LOS after CABG, independent of known confounders. Prolonged LOS in patients with SDB may be due to increased postoperative hemodynamic instability due to any cause.


Assuntos
Ponte de Artéria Coronária/métodos , Complicações Pós-Operatórias/epidemiologia , Apneia do Sono Tipo Central/complicações , Apneia Obstrutiva do Sono/complicações , Idoso , Ponte de Artéria Coronária/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Apneia do Sono Tipo Central/epidemiologia
18.
PLoS One ; 13(4): e0193558, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29652895

RESUMO

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure used to treat degenerative heart valve disease. The implantation requires a highly specific and interdisciplinary management approach. Currently, TAVI is performed with the patient under local or general anaesthesia. METHODS: This study was a retrospective analysis of all TAVI procedures performed at the University Hospital of Regensburg between January 2009 and July 2015. All pre-, intra and postoperative data focusing on perioperative complications were recorded. RESULTS: A total of 853 transfemoral- and transapical-TAVI patients were included in the study. All patients underwent general anaesthesia. The ASA classifications were primarily 3-4. The average logistic EuroScores for the transfemoral- and transapical-TAVI patients were 18 ± 12% and 21 ± 15% (p = 0.002), respectively. The anaesthesia coverage time was 170 ± 49 min., including 37 ± 12 minutes for anaesthetic management. Overall, 458 complications were recorded; with pneumonia, acute renal failure, indication for a permanent pacemaker and non-extubation in the operating theatre the most frequently recorded complications. CONCLUSION: In the present study, we showed that our patients' outcomes are comparable to those reported in the available literature. Compared to TF, TA patients show an overall worse physical condition as well as a higher perioperative morbidity and mortality. Consequently TA patients need additional care and should only be operated in appropriately experienced medical centres.


Assuntos
Anestesia Geral/efeitos adversos , Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Pneumonia/etiologia , Insuficiência Renal/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/métodos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento
19.
Thorac Cardiovasc Surg ; 66(8): 645-650, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-28780766

RESUMO

BACKGROUND: The aim of this retrospective study was to evaluate our experience with the surgical pericardiectomy procedure for patients suffering from isolated severe constrictive pericarditis. METHODS: From 1995 to 2016, 39 patients underwent isolated pericardiectomy for constrictive pericarditis. Fifteen patients were excluded because of concomitant surgery. There were 31 male (79.5%) patients and 8 female (20.5%) patients, 28 to 76 years old (mean, 56.6 ± 13.6 years). The underlying etiologies were idiopathic pericarditis (74.5%), infection (10%), rheumatic disorders (8%), status post cardiac surgery (2.5%), tuberculosis (2.5%), and status post mediastinal irradiation (2.5%). RESULTS: Pericardiectomy was performed through midline sternotomy in all cases. Sixteen patients (41%) underwent pericardiectomy electively employing cardiopulmonary bypass with the heart beating, and 23 patients (59%) had surgery without extracorporeal circulation (ECC). The overall 30-day mortality rate was 50% if cardiopulmonary bypass was used (13.8% since 2007). If surgery was performed without a heart-lung machine, mortality was 0%. On-pump patients had a significantly longer intensive care unit (ICU) stay (12 ± 9 vs. 4 ± 4 days, p = 0.013). Likewise, the duration of mechanical ventilation was much longer (171 ± 246 vs. 21 ± 40 hours, p = 0.04). The hospital stay was comparable with 28 ± 10 and 24 ± 18 days (p = 0.21). CONCLUSION: The present study demonstrates that pericardiectomy, without the use of cardiopulmonary bypass as treatment for constrictive pericarditis, is a safe procedure with an excellent outcome in critically ill patients.


Assuntos
Pericardiectomia , Pericardite Constritiva/cirurgia , Adulto , Idoso , Ponte Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Feminino , Alemanha , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pericardiectomia/efeitos adversos , Pericardiectomia/mortalidade , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Esternotomia , Fatores de Tempo , Resultado do Tratamento
20.
Resuscitation ; 121: 166-171, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28916477

RESUMO

BACKGROUND: Good neurological outcome is a major determinant after cardiac resuscitation. Extracorporeal life support may rapidly stabilize the patient, but cerebral ischemia remains a frequent complication relevant for further therapy. The aim of this study was to prove the value of NSE to indicate cerebral injury in patients with extracorporeal support after CPR. METHODS: 159 patients with CPR were included. NSE 48h peak levels and trends were tested for usability as predictive marker of brain injury, in-hospital mortality and long-term outcome. RESULTS: Overall mortality in this cohort was 53.5%. Incidence of relevant brain injury was 34.6% with severe diffuse hypoxia in 23.2%. NSE peaks were comparable in patients with and without focal ischemia, but were increased in patients with severe diffuse hypoxic injury (p<0.0001). ROC analysis (area under the curve) of peak values indicating brain injury and in-hospital mortality was 0.73 (95% confidence interval [CI] 0.65-0.82) and 0.74 (95% CI 0.66-0.81), respectively. NSE increased in 56.6% of patients with a sensitivity of 0.82 (95% CI 0.69-0.92) and a specificity of 0.43 (CI 0.0.31-0.55) indicating cerebral injury. Sensitivity and specificity of NSE peak levels >100µg/L was 0.6 (CI 0.49-0.72) and 0.74 (CI 0.63-0.84). In-hospital mortality of patients with NSE >100µg/L was 71.7%. 46.2% of discharged patients are in good neurological status (cerebral performance category scale [CPC] 1-2). Patients with NSE <100µg/L showed an in-hospital mortality of 36.4%, and good neurological status in 67.9%. CONCLUSION: NSE monitoring reliably indicates relevant cerebral injury in patients on extracorporeal support after cardiopulmonary resuscitation.


Assuntos
Isquemia Encefálica/sangue , Reanimação Cardiopulmonar/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Fosfopiruvato Hidratase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Humanos , Hipóxia/sangue , Hipóxia/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
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