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1.
Int J Mol Sci ; 21(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33171904

RESUMO

Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods: Patients with sepsis (n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results: Kaplan-Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion: The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/genética , Sepse/genética , Sepse/mortalidade , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genótipo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Heterozigoto , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Índice de Gravidade de Doença
2.
Perfusion ; 31(5): 436-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26519742

RESUMO

The left ventricular assist device (LVAD) is now a routine therapy for advanced heart failure. The thoracotomy approach for LVAD implantation, in which the left ventricle is approached through a pericardial rent, is becoming popular. We demonstrate closure of the pericardial rent with a polytetrafluoroethylene (PTFE) patch and its advantages.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Procedimentos Cirúrgicos Minimamente Invasivos , Implantação de Prótese/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Politetrafluoretileno , Toracotomia
3.
J Transl Med ; 12: 177, 2014 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-24950711

RESUMO

BACKGROUND: Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3'-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype. METHODS: Adult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure. RESULTS: A total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections. CONCLUSIONS: These results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.


Assuntos
Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/genética , Falência Hepática/genética , Polimorfismo Genético , Insuficiência Renal/genética , Sepse/genética , Receptor 4 Toll-Like/genética , Idoso , Transtornos da Coagulação Sanguínea/complicações , Feminino , Humanos , Falência Hepática/complicações , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Sepse/complicações
4.
Transpl Int ; 27(11): 1183-91, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25070600

RESUMO

Lung transplantation (LTx) from "extended donor criteria" donors may reduce significantly organ shortage. However, its influence on results remains unclear. In this study, we evaluate retrospectively the results of LTx from donors outside standard criteria: PaO2/FiO2 ratio < 300 mmHg, age over 55 years, and history of smoking > 20 pack-years. Two hundred and forty-eight patients underwent first time LTx in our institution between January 2007 and January 2013. Seventy-nine patients (Group I) received organs from "extended donor criteria" and 169 patients (Group II) from "standard donor criteria." Recipients' and donors' demographics, perioperative variables, and outcome were compared. Donors from Group I were significantly older [median (interquartile range)]: 52.5 (44;58) vs. 42 (28.5;48.5) years (P < 0.001) with lower PaO2/FiO2 ratio: 366 ± 116.1 455 ± 80.5 mmHg (P < 0.001), higher incidence of smoking history: 57.7% vs. 41.8% (P = 0.013), and more extensive smoking history: 24(15;30) vs. 10(3.75;14) pack-years (P < 0.001). Other parameters were comparable. Recipients' gender, diagnosis, percentage of patients operated on pump and receiving double LTx were also comparable. Recipients from Group I were significantly older: 50 (42;57) vs. 44 (29.5;53.5) years (P = 001). There were no differences observed in recipients' prevalence of primary graft dysfunction (PGD) grade 3 over first three postoperative days, duration of mechanical ventilation, intensive care and hospital length of stay, prevalence of rejection, and bronchiolitis obliterans syndrome (BOS). 90-day, 1-year, and 5-year survival (Group I vs. II) were also similar: 88.6% vs. 91.7%, 83.2% vs. 84.6%, and 59% vs. 68.2% (log rank P = 0.367). Carefully selected donor lungs from outside the standard acceptability criteria may expand existing donor pool with no detrimental effect on LTx outcome.


Assuntos
Seleção do Doador/métodos , Transplante de Pulmão , Doadores de Tecidos , Adulto , Morte Encefálica , Bronquiolite Obliterante/etiologia , Morte , Seleção do Doador/normas , Feminino , Rejeição de Enxerto/etiologia , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Disfunção Primária do Enxerto/etiologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Coleta de Tecidos e Órgãos/métodos , Resultado do Tratamento
5.
Artif Organs ; 38(11): 940-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24788069

RESUMO

Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory assist method that offers circulatory as well as respiratory support efficiently via peripheral access; however, it is liable to complications. Limb ischemia is one of the notorious complications of ECMO but can be avoided utilizing a proper distal limb perfusion method. A retrospective study of patients undergoing peripheral venoarterial (VA) ECMO for various reasons between June 2010 and December 2012 was performed. All patients were evaluated by our multidisciplinary team for suitability as candidates for ECMO. A peripheral VA-ECMO circuit was implanted via groin: inflow cannula in the femoral vein, an outflow cannula and distal-perfusion cannula, or an introducer sheath in the femoral artery. During the study period, 83 patients underwent various types of ECMO; 45 received peripheral VA-ECMO. Distal limb perfusion was achieved with an introducer sheath (6-8 Fr) in 13 cases and with a distal-perfusion cannula (10-12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. One patient required a below-knee amputation. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly higher for the introducer sheath compared with the cannula (30.6 vs. 15.6% and 15.4 vs. 6.25%, respectively). Moreover, the patients supported on ECMO with a distal-perfusion cannula spent a significantly longer time on ECMO compared with the ones in whom an introducer sheath was used (11.9 ± 9.1 vs. 7.7 ± 4.3 days). The mean cannula size was significantly greater than the mean introducer sheath size (11.1 ± 1.3 vs. 7.0 ± 1.1 Fr). Use of a distal-perfusion cannula is a most reliable method of limb perfusion in peripheral VA-ECMO. The cannula can ensure adequate and smooth perfusion of the limb owing to its large caliber, its less turbulent flow, the ability it provides to monitor the flow, and the option to attach a side port.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Cardiopatias/terapia , Isquemia/etiologia , Perna (Membro)/irrigação sanguínea , Adulto , Cateterismo Periférico , Oxigenação por Membrana Extracorpórea/instrumentação , Feminino , Humanos , Isquemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
J Artif Organs ; 17(4): 370-2, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25103222

RESUMO

In this case report, we describe a 66-year-old patient with a massive LV aneurism which resulted after myocardial infarction. Due to severe LV function impairment, it was decided to perform left ventricular reconstruction surgery and, at the same time, left ventricular assist device implantation as a bridge to transplantation. The entire procedure was completed without using any patch material. The patient had an uneventful recovery and was discharged home after 18 days. After 1-year follow-up no adverse events were observed.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar , Procedimentos de Cirurgia Plástica/métodos , Idoso , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Resultado do Tratamento
7.
J Artif Organs ; 17(3): 228-35, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24880478

RESUMO

Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and mortality, whereas refractory cases require mechanical circulatory support. The aim of this study was to evaluate factors influencing survival during short-term ventricular assist support in PCCS. In total, 154 CentriMag(®) (Thoratec; CA, USA) devices were implanted for cardiogenic shock between 2004 and 2011 out of which 31 were for PCCS. A retrospective review was performed in 31 PCCS patients who required the CentriMag short-term VAD as a bridge to decision. Survivors and non-survivors were compared with respect to pre- and intra-operative characteristics as well as duration of short-term VAD support. Mean duration of support was 11.7 ± 15.4 days (range 1-65 days). Seventeen (54.83 %) patients died on support, 14 (45.16 %) were weaned off or upgraded to long-term device, while 11 (35.5 %) were discharged home. The overall survival to myocardial recovery and device explantation, or upgrade to a long-term VAD, was 41.9 % (n = 13) at the study cutoff. EuroSCORE II was significantly higher in non-survivors as compared to survivors (p = 0.047). The duration of short-term VAD support was significantly longer in survivors (p < 0.001). The CentriMag is a versatile, safe and effective short-term circulatory support for patients with PCCS as a bridge to decision which enables longer support and better recovery of both heart and end-organ function and thus may improve the survival of PCCS patients. Lower EuroSCORE may be essential for myocardial recovery in PCCS.


Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Complicações Pós-Operatórias/mortalidade , Choque Cardiogênico/terapia , Desenho de Equipamento , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Reino Unido/epidemiologia
8.
ASAIO J ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38569184

RESUMO

Severe right heart failure, often overlooked and challenging to manage, has prompted a growing interest in innovative approaches to provide functional support. This study uses experimentation in large porcine models to introduce a novel prototype of a pulsatile mechanical circulatory support device and document its effects when deployed as a right ventricular assist device (RVAD). The pulsatile ventricular assist platform (pVAP), featuring a membrane pump driven by an intra-aortic balloon pump console, actively generates pulsatile flow to propel right ventricular blood into the pulmonary artery. This novel prototype demonstrates promising potential in addressing the challenges of right heart failure management. After preliminary in vitro assessments, the pVAP was tested on seven porcine models in a healthy state and after the induction of right ventricular failure. During the procedure, a set of standard (ie, standard-of-care) hemodynamic measurements was obtained. Additionally, invasive pressure-volume loop analysis was employed to examine left ventricular hemodynamics. Results indicated that activation of the pVAP during right ventricular failure significantly improved systemic hemodynamics and enhanced left ventricular function. This study sheds light on the potential of the pVAP in managing right heart failure.

9.
Artif Organs ; 37(1): E40-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23305586

RESUMO

Although the mechanisms of neurological disorders after cardiac surgery in neonates are still not fully understood, alterations in blood flow after cardiopulmonary bypass (CPB) may lead to cerebral injury. The aim of the study was the analysis of flow changes in the carotid artery of neonatal piglets after CPB. Ten neonatal piglets (younger than 7 days) were connected to the CPB and further management underwent three steps: (i) cooling to 32°C core temperature within 30 min; (ii) cardiac arrest under cardioplegic myocardial protection for 90 min; and (iii) rewarming to 37°C after cross-clamp release (60 min of reperfusion). In summary, piglets were separated from CPB after a total duration time of 180 min. The blood flow was measured in the left carotid artery by an ultrasonic flow probe before CPB (baseline), immediately after CPB, 30 min, and 60 min after CPB. Additionally, the pulsatility index and the resistance index were calculated and compared. Finally, the relation of the carotid artery flow data with the corresponding pressure data at each time point was compared. After termination of CPB, the carotid artery mean flow was reduced from 28.34 ± 13.79 mL/min at baseline to 20.91 ± 10.61 mL/min and remained reduced 30 and 60 min after CPB termination (19.71 ± 11.11 and 17.64 ± 15.31 mL/min, respectively). Both the pulsatility and the resistance index were reduced immediately after CPB termination and increased thereafter. Nevertheless, values did not reach statistical significance. In conclusion, the carotid Doppler flow immediately after CPB and mild hypothermia in neonatal piglets was lower than before CPB due to reduced vascular resistance. Additionally, the pressure-flow relation revealed that immediately after CPB, a higher pressure is required to obtain adequate flow.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ponte Cardiopulmonar , Artérias Carótidas/fisiologia , Circulação Cerebrovascular/fisiologia , Hipotermia Induzida , Análise de Variância , Animais , Animais Recém-Nascidos , Artérias Carótidas/diagnóstico por imagem , Hemodinâmica , Fluxo Pulsátil , Suínos , Ultrassonografia , Resistência Vascular
10.
Artif Organs ; 37(10): 927-32, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23635326

RESUMO

Renal blood flow (RBF) may vary during cardiopulmonary bypass and low flow may cause insufficient blood supply of the kidney triggering renal failure postoperatively. Still, a valid intraoperative method of continuous RBF measurement is not available. A new catheter combining thermodilution and intravascular Doppler was developed, first calibrated in an in vitro model, and the catheter specific constant was determined. Then, application of the device was evaluated in a pilot study in an adult cardiovascular population. The data of the clinical pilot study revealed high correlation between the flow velocities detected by intravascular Doppler and the RBF measured by thermodilution (Pearson's correlation range: 0.78 to 0.97). In conclusion, the RBF can be measured excellently in real time using the new catheter, even under cardiopulmonary bypass.


Assuntos
Procedimentos Cirúrgicos Cardíacos/instrumentação , Circulação Renal , Idoso , Ponte Cardiopulmonar/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
11.
Heart Surg Forum ; 16(4): E208-9, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23958533

RESUMO

Myocarditis is a known extraintestinal manifestation of inflammatory bowel diseases, but it rarely leads to acute cardiac pump failure. We report a case of fulminant myocarditis associated with ulcerative colitis treated successfully with an extracorporeal membrane oxygenator.


Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/terapia , Oxigenação por Membrana Extracorpórea/métodos , Miocardite/etiologia , Miocardite/terapia , Adulto , Colite Ulcerativa/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Miocardite/diagnóstico , Resultado do Tratamento
12.
Emerg Med J ; 30(12): 1012-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23307754

RESUMO

SUMMARY: In the previous and the current guidelines of the European Resuscitation Council (ERC), endotracheal intubation (ETI), as an instrument for ventilation during resuscitation, was confirmed as less important for paramedics not trained in this method. For those, during resuscitation, the laryngeal tube is recommended by the ERC as a supraglottic airway device. The present study investigated prospectively the use of the laryngeal tube disposable (LT-D) by paramedics in prehospital emergency cases. METHODS: During a 42-month period (Sept 2008-Feb 2012), we prospectively registered all prehospital cardiac arrest situations in which the LT-D had been applied by paramedics (from one emergency medical service in Germany). RESULTS: During the defined period, 133 attempts, recorded on standardised data sheets, were enrolled into the investigation. Three were excluded from the study because of use during a trauma situation. Therefore, 130 patients were evaluated in this study. For this, the LT-D was used in 98% of all cases during resuscitation, and in about 2% of other emergencies (eg, trauma). With regard to resuscitation, adequate ventilation/oxygenation was described as possible in 83% of all included cases. In 66% of all cases, no problems concerning the insertion of the LT-D were described by the paramedics. No significant problems were reported in 93%. In 7% (n=9 cases), no insertion of the LT-D was possible. Instead of bag-mask-valve ventilation, the LT-D was used as a first-line airway device in about 66%. Between the two defined groups, no statistically significant differences were found (p>0.05). CONCLUSIONS: As an alternative airway device during resuscitation, recommended by the ERC in 2005 and 2010, the LT-D may enable ventilation rapidly and, as in most of our described cases, effectively. Additionally, by using the LT-D in a case of cardiac arrest, a reduced 'hands-off time' and, therefore, a high chest compression rate may be possible. Our investigation showed that the LT-D was often used as an alternative to bag-mask-ventilation and to ETI as well. However, we were able to describe more problems in the use of the LT-D than earlier investigations. Therefore, in future, more studies concerning the use of alternative airway devices in comparison with ETI and/or video-laryngoscopy seem to be necessary.


Assuntos
Reanimação Cardiopulmonar/métodos , Equipamentos Descartáveis , Serviços Médicos de Emergência , Parada Cardíaca/terapia , Intubação Intratraqueal/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicina de Emergência/métodos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
13.
Crit Care ; 16(4): R153, 2012 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-22889236

RESUMO

INTRODUCTION: Pronounced extracellular acidosis reduces both cardiac contractility and the ß-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the ß-adrenergic response of isolated trabeculae from human end-stage failing hearts. METHODS: Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10(-6) M). RESULTS: A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm(2); n = 12; P < 0.01) as compared with pH 7.40. Force-frequency relation measurements yielded no further significant differences of twitch force. At the maximal isoproterenol concentration, the force amplitude was comparable in each of the two groups (pH 7.40 versus pH 7.20). However, the half-maximal effective concentration (EC50) was significantly increased in the acidosis group, with an EC50 of 5.834 × 10(-8) M (confidence interval (CI), 3.48 × 10(-8) to 9.779 × 10(-8); n = 9), compared with the control group, which had an EC50 of 1.056 × 10(-8) M (CI, 2.626 × 10(-9) to 4.243 × 10(-8); n = 10; P < 0.05), indicating an impaired ß-adrenergic force response. CONCLUSIONS: Our data show that mild metabolic acidosis reduces cardiac contractility and significantly impairs the ß-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure.


Assuntos
Acidose/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Coração/fisiopatologia , Contração Miocárdica/fisiologia , Receptores Adrenérgicos beta/fisiologia , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Isoproterenol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos
14.
Pacing Clin Electrophysiol ; 35(4): e105-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21745225

RESUMO

We describe a case of 83-year-old man who was admitted to our department for treatment of recurrent device-pocket infections. Our report shows that in a case of high-risk patient with a complicated cardiac implantable electric devices infection involving multidrug-resistent gram-positive pathogen, the application of daptomycin in combination with staged surgical therapy can be efficient and safe.


Assuntos
Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Desfibriladores Implantáveis/microbiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus haemolyticus/efeitos dos fármacos , Idoso de 80 Anos ou mais , Remoção de Dispositivo/efeitos adversos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos , Masculino , Infecções Estafilocócicas/diagnóstico , Resultado do Tratamento
16.
J Clin Med ; 10(22)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34830585

RESUMO

(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan-Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, p = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, p = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.

17.
Artif Organs ; 34(11): 961-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21092038

RESUMO

Several genetic polymorphisms have been identified to play a role in the occurrence and progression of renal dysfunction after cardiac surgery with cardiopulmonary bypass (CPB). Recently, it was demonstrated that the T allele of SNP rs1617640 in the promoter of the erythropoetin (EPO) gene is significantly associated with proliferative diabetic retinopathy (PDR) and end-stage renal disease (ESRD) due to increased EPO expression. This disease risk-associated gene and its potential pathway mediating severe microvascular complications in T-allele carriers could also play a role on renal dysfunction in patients who underwent cardiac surgery with CPB. We hypothesized that the patients' ability to produce increased EPO concentrations will affect morbidity and mortality after CPB. We conducted a prospective single center study between April 2006 and May 2007. In 481 patients who underwent cardiac surgery with CPB we prospectively examined the SNP rs1617640 in the promoter of the EPO gene by DNA sequencing. The patients were grouped according to their genotype (GG, GT, and TT). The genotype distribution of SNP rs1617640 in the promoter of the EPO gene was 36% (TT), 49% (TG), and 15% (GG). There was no difference in age, body mass index, gender, CPB time, or length of stay in intensive care unit. The hospitalization was irrespective of the patients' genotypes. The baseline creatinine in the TT group was 0.2 points higher than in the other groups; however this was without statistical significance in the multivariate analysis. No significant difference was shown in Euroscore, the Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation Score II, Acute Renal Failure Score, or the Risk, Injury, Failure, Loss of Kidney Function Score. The mortality was equal across the genotypes. However, an association between the TT genotype and acute renal replacement therapy (P=0.03), intra-aortic balloon pump usage (P=0.02), and serum creatine phosphokinase-MB increase (P=0.03) were observed after cardiac surgery. Our analysis suggests that the risk allele (T) of rs1617640 plays a role in the development of renal dysfunction after cardiac surgery with CPB. Patients with the TT risk allele required more frequent acute renal replacement therapy. Since our result is close to the border of significance, this hypothesis should be investigated in larger prospective studies with long-term follow-up to emphasize this polymorphism as a potential risk factor.


Assuntos
Injúria Renal Aguda/genética , Injúria Renal Aguda/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Eritropoetina/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Terapia de Substituição Renal , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Idoso , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ponte Cardiopulmonar/mortalidade , Distribuição de Qui-Quadrado , Creatina Quinase Forma MB/sangue , Creatinina/sangue , Feminino , Frequência do Gene , Predisposição Genética para Doença , Alemanha , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Estudos Prospectivos , Medição de Risco , Fatores de Risco
18.
Artif Organs ; 34(11): 969-79, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21092039

RESUMO

We established a stable and reproducible animal model of chronic heart failure (CHF) in sheep to investigate biomolecular changes. Therefore, two biomarkers, adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial growth factor-A (VEGF-A) were examined to reveal their role during chronic ischemic conditions of the heart. AMPK was studied because it plays an important role in cellular energy homeostasis and its upregulation is associated with myocardial ischemia, whereas VEGF-A was studied because it acts as an important signaling protein for neoangiogenesis. We examined 15 juvenile sheep (mean weight, 78±4kg; control, n=3; ShamOP, n=2; coronary microembolization [CME], n=10). CHF was induced under fluoroscopic guidance by multiple sequential microembolizations (MEs) through bolus injection of polysterol microspheres (90µm, n=25.000) into the left main coronary artery. CME was repeated up to three times at 2- to 3-week intervals until animals started to develop stable signs of CHF. All animals were followed for 3 months. Phosphorylation of AMPK, marking the activated protein form, was detected by Western blotting. VEGF-A and vascular endothelial growth factor-receptor 2 (VEGF-R2) mRNA were detected by real-time polymerase chain reaction. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was used as a reference housekeeping gene. All 10 CHF animals developed clinical signs of CHF as indicated by a significant decrease of cardiac output, decreased ejection fraction, as well as occurrence of tachycardia and tachypnoea. Western blots showed significant phosphorylation of AMPK in CME animals compared to the control group (phospho-adenosine monophosphate-activated protein kinase α) (GAPDH control: 0.0, CME left ventricle [LV]: 0.39±0.20, CME right ventricle [RV]: 0.53±0.30; P<0.05). VEGF-A and VEGF-R2 expression in CME animal myocardium was within the range of the control group, but this data did not reach statistical significance due to the small size of this group. While microinjection was performed into the left main coronary artery, phosphorylation of AMPK and expression of VEGF-A and VEGF-R2 were significantly higher in the RV than in the LV. Multiple sequential intracoronary MEs can effectively induce myocardial dysfunction with clinical and biomolecular signs of chronic ischemic cardiomyopathy. Quantitative analysis of biomolecular markers showed a significantly higher phosphorylation of AMPK in CHF animals compared with control myocardium.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Insuficiência Cardíaca/enzimologia , Miocárdio/enzimologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Biomarcadores/metabolismo , Western Blotting , Doença Crônica , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/enzimologia , Injeções Intra-Arteriais , Microesferas , Fosforilação , Poliestirenos/administração & dosagem , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ovinos , Fatores de Tempo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
19.
Langenbecks Arch Surg ; 394(2): 357-62, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18509670

RESUMO

BACKGROUND AND AIMS: External support of vein grafts by fibrin glue possibly prevents overdistension, vascular remodeling, and neointimal hyperplasia. Previous animal models of neointimal hyperplasia showed conflicting results. Here, long-term effects of external fibrin glue support were studied in a new rat model of jugular vein to abdominal aorta transposition. MATERIALS AND METHODS AND METHODS: In male Wistar rats (250-300 g) right jugular vein (1.0-1.5 cm) was transposed to the infrarenal aorta. Fibrin glue (0.25 ml) covered the vein before releasing the vascular clamps (n = 6). Control vein grafts were exposed directly to blood pressure. After 16 weeks vein grafts were pressure-fixed for histology. Intima thickness, luminal and intimal area were measured by planimetry and elastic fibers demonstrated by Elastica van Giesson staining. RESULTS: Intimal thickness (74.04 +/- 6.7 microm vs 1245 +/- 187 microm, control vs fibrin treatment; p < 0.001), intimal area (2517.16 +/- 355 mm(2) vs 18424 +/- 4927 mm(2), control vs fibrin treatment; p < 0.05) and luminal area (2184.75 +/- 347 mm(2) vs 7231.85 +/- 1782 mm(2), control vs fibrin treatment; p < 0.05) were significantly increased, elastic fibers in the vessel wall were diminished and the vessel wall infiltrated by mononuclear cells in fibrin glue supported veins. CONCLUSION: External support of vein grafts by fibrin glue leads to aneurysmal degeneration and intimal hyperplasia, thereby possibly jeopardizing long-term graft patency.


Assuntos
Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/induzido quimicamente , Adesivo Tecidual de Fibrina/efeitos adversos , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia , Veias/transplante , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/patologia , Tecido Elástico/patologia , Oclusão de Enxerto Vascular/induzido quimicamente , Oclusão de Enxerto Vascular/patologia , Hiperplasia , Masculino , Ratos , Ratos Wistar , Veias/patologia
20.
Ann Vasc Surg ; 22(4): 520-4, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18538981

RESUMO

We examined data of 21 patients who were treated with selective perfusion of both renal arteries with 500 mL of 8 degrees C histidine-tryptophan-ketoglutarate (HTK) solution each for renal protection during aortic surgery. Only the data from aortic surgeries with unavoidable suprarenal aortic cross-clamping for juxtarenal or suprarenal abdominal aortic aneurysms (AAAs) or high Leriche syndrome accompanied with stenosis of renal arteries are presented. Five patients underwent immediate surgery because of perforation of an AAA; the other 16 patients went through elective surgeries. In three cases (14%) stenosis of the renal arteries was diagnosed; nevertheless, implantation of an aortorenal bypass was necessary in seven patients. In total, 14 aortorenal bypasses were implanted (five venous grafts and nine prosthesis grafts). Four (19%) patients needed catecholaminergic support to establish stable circulatory conditions; in two (9%) of these cases additional ischemia of the colon was observed and sigmoidectomy was performed. All of these four patients underwent immediate surgery, and one died after surgery because of severe sepsis. In four cases postsurgical renal insufficiency was observed. Three of these patients were admitted for emergency surgery because of their hemodynamic situation due to perforation of the AAA. None of the patients needed chronic dialysis after surgery. Whereas in all patients who underwent elective surgery the renal function remained stable as judged by postoperative serum creatinine values, in five out of seven patients with aortorenal bypass surgery the renal function improved. Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients undergoing elective surgery with suprarenal cross-clamping of the aorta.


Assuntos
Aorta Abdominal/cirurgia , Soluções Cardioplégicas , Hipotermia Induzida , Rim/irrigação sanguínea , Idoso , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Creatinina/sangue , Feminino , Glucose , Humanos , Rim/fisiopatologia , Síndrome de Leriche/complicações , Síndrome de Leriche/cirurgia , Masculino , Manitol , Cloreto de Potássio , Procaína , Obstrução da Artéria Renal/complicações , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Procedimentos Cirúrgicos Vasculares/efeitos adversos
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