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1.
Am J Infect Control ; 52(8): 906-914, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38437883

RESUMO

BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.


Assuntos
Infecções Relacionadas a Cateter , Unidades de Terapia Intensiva , Infecções Urinárias , Humanos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controle , Ásia/epidemiologia , América Latina/epidemiologia , Oriente Médio/epidemiologia , Masculino , Feminino , Europa Oriental/epidemiologia , Controle de Infecções/métodos , Pessoa de Meia-Idade , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Idoso
2.
Infect Control Hosp Epidemiol ; : 1-11, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37114756

RESUMO

OBJECTIVE: To identify central-line (CL)-associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs). DESIGN: From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms. SETTING: The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PATIENTS: In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs. METHODS: For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs). RESULTS: The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03-1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03-1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03-1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23-1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31-4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22-3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09-2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11-6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57-3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81-3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71-3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96-2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02-2.18; P = .04). CONCLUSIONS: The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

3.
J Infect Public Health ; 15(9): 950-954, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35917656

RESUMO

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.


Assuntos
Gestão de Antimicrobianos , Doenças Transmissíveis , Infecção Hospitalar , Antibacterianos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Humanos , Controle de Infecções , Unidades de Terapia Intensiva , Autorrelato , Inquéritos e Questionários
4.
J Infect Dev Ctries ; 16(6): 1081-1088, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35797304

RESUMO

INTRODUCTION: Although vaccines are the safest and most effective means to prevent and control infectious diseases, the increasing rate of vaccine hesitancy and refusal (VHR) has become a worldwide concern. We aimed to find opinions of parents on vaccinating their children and contribute to available literature in order to support the fight against vaccine refusal by investigating the reasons for VHR on a global scale. METHODOLOGY: In this international cross-sectional multicenter study conducted by the Infectious Diseases International Research Initiative (ID-IRI), a questionnaire consisting of 20 questions was used to determine parents' attitudes towards vaccination of their children. RESULTS: Four thousand and twenty-nine (4,029) parents were included in the study and 2,863 (78.1%) were females. The overall VHR rate of the parents was found to be 13.7%. Nineteen-point three percent (19.3%) of the parents did not fully comply with the vaccination programs. The VHR rate was higher in high-income (HI) countries. Our study has shown that parents with disabled children and immunocompromised children, with low education levels, and those who use social media networks as sources of information for childhood immunizations had higher VHR rates (p < 0.05 for all). CONCLUSIONS: Seemingly all factors leading to VHR are related to training of the community and the sources of training. Thus, it is necessary to develop strategies at a global level and provide reliable knowledge to combat VHR.


Assuntos
Doenças Transmissíveis , Hesitação Vacinal , Criança , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , Vacinação
5.
Eur J Clin Microbiol Infect Dis ; 40(11): 2323-2334, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34155547

RESUMO

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.


Assuntos
Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Unidades de Terapia Intensiva/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto Jovem
6.
Am J Infect Control ; 49(10): 1267-1274, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33901588

RESUMO

BACKGROUND: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. METHODS: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. RESULTS: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. CONCLUSIONS: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.


Assuntos
Infecções Bacterianas , Infecções Relacionadas a Cateter , Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Infecções Urinárias , Adulto , Infecções Bacterianas/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Criança , Infecção Hospitalar/epidemiologia , Humanos , Controle de Infecções , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Estudos Prospectivos , Infecções Urinárias/epidemiologia
7.
J Med Microbiol ; 68(12): 1723-1731, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31746726

RESUMO

Introduction. Carbapenems are often described as the most effective weapon against infections caused by multidrug-resistant bacteria especially those belonging to the group of non-fermenting bacteria such as Pseudomonas. The main mechanisms leading to resistance are the hyperexpression of certain efflux pumps belonging to the resisto-nodular division and the lower expression of the transmembrane porin OprD, sometimes in combination with excessive production of the intrinsic AmpC. Carbapenemases are assumed to play a secondary role.Aim. The aim of this study was to determine the exact mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from the largest Bulgarian University hospital 'St. George'- Plovdiv.Methodology. A total of 32 clinical isolates collected from different patients' samples resistant to imipenem and/or meropenem were examined via phenotypic and molecular-genetic tests.Results. No metallo-enzyme production was detected. Three isolates were positive for OXA-50-encoding genes in two of them in combination with other oxacillinases or the bla VEB-1 gene. For the first time, OXA-50-producing P. aeruginosa have been reported in Bulgaria. The increased expression or hyperexpression of MexXY-OprM efflux pump was observed as the main mechanism of resistance. In most cases, it was combined with lower expression or lack of OprD with or without MexAB-OprM hyperexpression. No excessive production of AmpC was detected in comparison to the reference ATCC 27853 P. aeruginosa strain.Conclusion. The increased expression or overexpression of MexXY-OprM efflux pumps is the leading cause of carbapenem resistance in our isolates Pseudomonas, detected in 94 % of the bacteria investigated.


Assuntos
Proteínas de Bactérias/análise , Proteínas de Bactérias/fisiologia , Carbapenêmicos/farmacologia , Porinas/fisiologia , Pseudomonas aeruginosa/isolamento & purificação , beta-Lactamases/análise , beta-Lactamases/fisiologia , Farmacorresistência Bacteriana , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia
8.
Folia Med (Plovdiv) ; 59(4): 413-422, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29341954

RESUMO

BACKGROUND: Production of Bla OXA-23, OXA-24, OXA-58 and hyperexpression of OXA-51 due to ISAba1 insertion sequence are the leading causes of carbapenem resistance in Acinetobacter baumannii. The loss of OprD transmembrane protein and the overexpression of some effl ux pumps are considered to be the main factors for carbapenem resistance in Pseudomonas aeruginosa whereas metallo-enzymes' production has a secondary role. AIM: Тo examine the carbapenem resistance due to carbapenemase production among clinically signifi cant Gram-negative non-fermenters from St George University hospital, Plovdiv: A. baumannii and P. aeruginosa. MATERIALS AND METHODS: Forty three A. baumannii and 43 P. aeruginosa isolates, resistant or with intermediate resistance to imipenem and/or meropenem were included in the study. They were collected from patients admitted in 14 various hospital wards between 2010 and 2014. Both phenotypic and genetic methods were used for identifi cation and antimicrobial susceptibility testing. RESULTS: All A. baumannii demonstrated carbapenemase production determined by a modifi ed Hodge test whereas P. aeruginosa isolates did not show this phenomenon. OXA-23 genes were determined in 97.7% (42 out of 43) of A. baumannii isolates indistinguishable from the sequence of the classical ARI-1 gene. OXA-24, OXA-58 and overexpression of OXA-51 were not registered in any of the isolates. All P. aeruginosa were negative for blaVIM and blaIMP genes. CONCLUSION: The leading cause of carbapenem resistance in A. baumannii isolates from our hospital is the carbapenemase production due to the expression of OXA- 23 gene, whereas in P. aeruginosa - the loss of transmembrane OprD protein and the effl ux pumps' hyperexpression are suspected to be the main mechanisms.


Assuntos
Acinetobacter baumannii/enzimologia , Proteínas de Bactérias/biossíntese , Pseudomonas aeruginosa/enzimologia , beta-Lactamases/biossíntese , Acinetobacter baumannii/efeitos dos fármacos , Bulgária , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Hospitais Universitários , Humanos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos
9.
Folia Microbiol (Praha) ; 62(2): 117-125, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27761725

RESUMO

The aim of this work is to study the epidemiology and antimicrobial resistance to the most commonly used antibiotics for the treatment of acute gastroenteritis caused by Salmonella and Shigella at the largest Bulgarian hospital-University Hospital "St. George," Plovdiv-for the period 2009-2013. Two hundred ninety strains were in vitro tested for resistance to 15 antimicrobial agents. The presence of extended-spectrum beta-lactamases (ESBLs) was demonstrated by a variety of specialized tests. For comparison, a collection of 28 strains submitted by the National Reference Laboratory (NRL) "Enteric Infections" at the National Center of Infectious and Parasitic Diseases (NCIPD), Sofia, was also tested for the production of ESBLs. In isolates, phenotypically demonstrated as ESBL producers, polymerase chain reaction (PCR) detection of the genes bla-CTX-M, bla-SHV, and bla-TEM was performed. Among the 290 tested isolates, only two- Salmonella serotype Livingstone and Shigella flexneri-were phenotypically proven to be ESBL producers. Only 4 strains from the collection of 28, submitted from the NRL "Intestinal Infections" in NCIPD, Sofia, were phenotypically confirmed as ESBL producers. The presence of the bla-CTX-M gene was detected in all of the tested strains (4 from NRL, NCIPD, Sofia, and 2 from the University Hospital St. George, Plovdiv), the bla-SHV gene only in strain S. Livingstone from Plovdiv, and the bla-TEM gene in two from Sofia and one (again S. Livingstone) from Plovdiv. In conclusion, Salmonella and Shigella isolates from patients hospitalized at the University Hospital St. George, Plovdiv, with acute gastroenteritis demonstrate good susceptibility to the most commonly used antibiotic agents, including azithromycin.


Assuntos
Farmacorresistência Bacteriana/genética , Disenteria Bacilar/tratamento farmacológico , Gastroenterite/tratamento farmacológico , Infecções por Salmonella/tratamento farmacológico , Salmonella/efeitos dos fármacos , Shigella/efeitos dos fármacos , Doença Aguda , Adolescente , Adulto , Antibacterianos/farmacologia , Bulgária/epidemiologia , Criança , Pré-Escolar , DNA Bacteriano/genética , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Feminino , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Expressão Gênica , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Salmonella/enzimologia , Salmonella/genética , Salmonella/crescimento & desenvolvimento , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Shigella/enzimologia , Shigella/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
10.
Am J Infect Control ; 44(12): 1495-1504, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27742143

RESUMO

BACKGROUND: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. METHODS: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. RESULTS: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. CONCLUSIONS: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Unidades de Terapia Intensiva , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Saúde Global , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
11.
Nanoscale Res Lett ; 8(1): 324, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23870782

RESUMO

We present a dispersion theory of the surface plasmon polaritons (SPP) in random metal-dielectric nanocomposite (MDN) consisting of bulk metal embedded with dielectric inclusions. We demonstrate that embedding of dielectric nanoparticles in metal results in the formation of the plasmonic bandgap due to strong coupling of the SPP at the metal-vacuum interface and surface plasmons localized at the surface of nanoinclusions. Our results show that MDN can replace metals in various plasmonic devices, which properties can be tuned in a wide spectral range. Being compatible with waveguides and other photonic structures, MDN offers high flexibility in the plasmonic system design.

12.
Ann Thorac Surg ; 96(2): 586-95, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23773730

RESUMO

BACKGROUND: The sarcoplasmic reticulum calcium ATPase (SERCA2a) is an important molecular regulator of contractile dysfunction in heart failure. Gene transfer of SERCA2a mediated by molecular cardiac surgery with recirculating delivery (MCARD) is a novel and clinically translatable strategy. METHODS: Ischemic heart failure was induced by ligation of OM1 and OM2 in 14 sheep. Seven sheep underwent MCARD-mediated AAV1-SERCA2a delivery 4 weeks after myocardial infarction, and seven sheep served as untreated controls. Magnetic resonance imaging-based mechanoenergetic studies were performed at baseline, 3 weeks, and 12 weeks after infarction. Myocyte apoptosis was quantified by Tdt-mediated nick-end labeling assay. Myocyte cross-sectional area and caspase-8 and caspase-9 activity was measured with imaging software, specific fluorogenic peptides, and immunohistochemistry. RESULTS: MCARD-mediated AAV1-SERCA2a gene delivery resulted in robust cardiac-specific SERCA2a expression and stable improvements in global and regional contractility. There were significantly higher stroke volume index, left ventricular fractional thickening, and ejection fraction at 12 weeks in the MCARD group than in the control group (30 ± 3 vs 21 ± 2 mL/m(2); 12% ± 5% vs 3% ± 3%; and 43 ± 4 vs 32 ± 4, respectively, all p < 0.05). Apoptotic myocytes were observed more frequently in the control group than in the MCARD-SERCA2a group (0.57.2 ± 0.16 AU vs 0.32.4 ± 0.08 AU, p < 0.05). MCARD-SERCA2a also resulted in decreased caspase-8 and caspase-9 expression and decreased myocyte area in the border zone of transgenic sheep compared with control sheep (14.6% ± 1.2% vs 2.9% ± 0.7%; 18.2% ± 1.9% vs 8.6% ± 1.4%; and 102.1 ± 3.8 µm(2) vs 88.1 ± 3.6 µm(2), all p < 0.05). CONCLUSIONS: MCARD-mediated SERCA2a delivery results in robust cardiac specific gene expression, improved contractility, and a decrease in both myocyte apoptosis and myocyte hypertrophy.


Assuntos
Terapia Genética/métodos , Insuficiência Cardíaca/cirurgia , Miócitos Cardíacos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/administração & dosagem , Animais , Procedimentos Cirúrgicos Cardíacos , Técnicas de Transferência de Genes , Miócitos Cardíacos/fisiologia , Ovinos
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