Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus.

INTRODUCTION: Low high-density lipoprotein (HDL)-cholesterol is frequent in patients with peripheral artery disease (PAD) and also in type 2 diabetes mellitus (T2DM), the major risk factor for PAD. The transfer of cholesterol from the other lipoproteins to HDL is an important aspect of HDL metabolism and function, and may contribute to atherogenic mechanisms that lead to PAD development. OBJECTIVE: The aim of this study was to investigate the status of cholesterol transfers in patients with PAD without or with T2DM. METHODS: Patients with PAD (n = 19), with PAD and T2DM (PAD + DM, n = 19), and healthy controls (n = 20), all paired for age, sex, and BMI were studied. Transfer of both forms of cholesterol, unesterified (UC) and esterified (EC), was performed by incubating plasma with a donor nanoemulsion containing radioactive UC and EC, followed by chemical precipitation and HDL radioactive counting. RESULTS: Low-density lipoprotein (LDL)-cholesterol and triglycerides were similar in the three groups. Compared to controls, HDL-C was lower in PAD + DM (p < 0.05), but not in PAD. Transfer of UC was lower in PAD + DM than in PAD and controls (4.18 ± 1.17%, 5.13 ± 1.44%, 6.59 ± 1.25%, respectively, p < 0.001). EC transfer tended to be lower in PAD + DM than in controls (2.96 ± 0.60 vs 4.12 ± 0.89%, p = 0.05). Concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), both involved in HDL metabolism, were not different among the three groups. CONCLUSION: Deficient cholesterol transfer to HDL may play a role in PAD pathogenesis. Since UC transfer to HDL was lower in PAD + DM compared to PAD alone, it is possible that defective HDL metabolism may contribute to the higher PAD incidence in patients with T2DM.Keywords.

Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats.

OBJECTIVES: The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage. METHODS: Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks). Treatments began on transplantation day. RESULTS: Thirty days post-transplantation, SYNG showed intact aortas. ALLO and ALLO+LDE presented intense neointimal formation. In ALLO+LDE-PTX, treatment inhibited neointimal formation; narrowing of aortic lumen was prevented in ALLO and ALLO+LDE. LDE-PTX strongly inhibited proliferation and intimal invasion by smooth muscle cells, diminished 4-fold presence of apoptotic/dead cells in the intima, reduced the invasion of aorta by macrophages and T-cells and gene expression of pro-inflammatory tumour necrosis factor-alpha (TNFα), interferon gamma (IFNγ) and interleukin-1 beta (IL-1ß). CONCLUSIONS: LDE-PTX was effective in preventing the vasculopathy associated with rejection and may offer a potent therapeutic tool for post-transplantation.

Does Prior Percutaneous Coronary Intervention Influence the Outcomes of Coronary Artery Bypass Surgery?

INTRODUCTION: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. METHODS AND RESULTS: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. CONCLUSION: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Does prior percutaneous coronary intervention influence the outcomes of coronary artery bypass surgery?

Abstract Introduction: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. Methods and Results: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. Conclusion: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Desenvolvimento de modelo clínico para predição da possibilidade de identificação da artéria de Adamkiewicz por angiotomografia / Development of a clinical model to predict the likelihood of identification of the Adamkiewicz artery by angiotomography

Contexto: Diferenças morfológicas da artéria de Adamkiewicz (AKA) entre a população portadora e não portadora de doença aórtica têm importância clínica, influenciando as complicações neuroisquêmicas da medula espinhal em procedimentos operatórios. Ainda não é conhecida a correlação entre parâmetros clínicos e a previsibilidade da identificação dessa artéria pela angiotomografia. Objetivo: Desenvolver um modelo matemático que, através de parâmetros clínicos correlacionados com aterosclerose, possa prever a probabilidade de identificação da AKA em pacientes submetidos a angiotomografias. Método: Estudo observacional transversal utilizando banco de imagens e dados de pacientes. Foi feita análise estatística multivariada e criado modelo matemático logit de predição para identificação da AKA. Variáveis significativas foram utilizadas na montagem da fórmula para cálculo da probabilidade de identificação. O modelo foi calibrado, e a discriminação foi avaliada pela curva receiver operating characteristic (ROC). A seleção das variáveis explanatórias foi guiada pela maior área na curva ROC (p = 0,041) e pela significância combinada das variáveis. Resultados: Foram avaliados 110 casos (54,5% do sexo masculino, com idade média de 60,97 anos e etnia com coeficiente B -2,471, M -1,297, N -0,971), com AKA identificada em 60,9%. Índice de massa corporal: 27,06 ± 0,98 (coef. -0,101); fumantes: 55,5% (coef. -1,614/-1,439); diabéticos: 13,6%; hipertensos: 65,5% (coef. -1,469); dislipidêmicos: 58,2%; aneurisma aórtico: 38,2%; dissecção aórtica: 12,7%; e trombo mural: 24,5%. Constante de 6,262. Fórmula para cálculo da probabilidade de detecção: ( ) ( ) . . . . . tan 1 ( 1) Coef Etnia Coef IMC IMC Coef fumante Coef HAS Coe f dislip Cons te e − + ×+ + + + − + . O modelo de predição foi criado e disponibilizado no link https://vascular.pro/aka-model. Conclusão: Com as covariáveis etnia, índice de massa corporal, tabagismo, hipertensão arterial e dislipidemia, foi possível criar um modelo matemático de predição de identificação da AKA com significância combinada de nove coeficientes (p = 0,042)

Background: There are clinically important morphological differences in the Adamkiewicz artery (AKA) between populations that do and do not have aortic disease and they have an influence on the neuroischemic complications involving the spinal cord during surgical operations. It is not yet known whether clinical parameters correlate with the predictability of identification of the artery using angiotomography. Objective: To develop a mathematical model that by correlating clinical parameters with atherosclerosis enables prediction of the probability of identification of the AKA in patients examined with angiotomography. Method: This is a cross-sectional, observational study using a patient database and image bank. A multivariate statistical analysis was conducted and a logit mathematical model was constructed to predict AKA identification. Significant variables were used to build a formula for calculation of the probability of identification. This model was calibrated and its power of discrimination was assessed using receiver operating characteristic (ROC) curves. Selection of explanatory variables was based on largest area under the ROC curve (p = 0.041) and combined significance of variables. Results: A total of 110 cases were analyzed (54.5% were male, mean age was 60.97 years, and ethnicity coefficients were white -2.471, brown -1.297, and black -0.971) and the AKA was identified in 60.9%. Body mass index: 27.06 ± 0.98 (coef. -0.101); smokers: 55.5% (coef. -1.614/-1.439); diabetes: 13.6%; hypertension: 65.5% (coef. -1.469); dyslipidemia: 58.2%; aortic aneurysm: 38.2%; aortic dissection: 12.7%; and mural thrombus: 24.5%. The constant was 6.262. The formula for calculating the probability of detection is as follows: ( ) ( ) . . . ker . . tan 1 ( 1) Coef Etnicity Coef BMI BMI Coef smo Coef SAH Coef dyslip Cons t e − + ×+ + + + − + . The prediction model was constructed and made available at: https://vascular.pro/aka-model. Conclusions: Using the covariates ethnicity, body mass index, smoking, arterial hypertension, and dyslipidemia, it proved possible to create a mathematical model for predicting identification of the AKA with a combined significance of nine coefficients (p = 0.042)

Predictors of Adamkiewicz artery and anterior spinal artery detection through computerized tomographic angiography.

BACKGROUND: The detection of the Adamkiewicz artery and the anterior spinal artery has been associated with the ability to prevent adverse spinal cord outcomes after aortic surgical procedures. Yet, to our knowledge, no previous studies have attempted to use modern predictive models to identify the most important variables in determining artery detectability. AIMS: To develop a model to predict the odds of visualizing the Adamkiewicz artery or anterior spinal artery in patients undergoing computerized tomographic angiography. METHODS: We conducted a prospective, cross-sectional study. Outcomes of interest were the non-detection of the Adamkiewicz artery and anterior spinal artery, and their corresponding level of origin. Axial images were inspected in high definition in search of two dense spots characterizing the Adamkiewicz artery and anterior spinal artery. A multiplanar three-dimensional reconstruction was then performed using the OsiriX® software. RESULTS: A total of 110 participants were part of this analysis. When evaluating risks for the Adamkiewicz artery being undetectable, significant factors could be classified into three broad categories: risk factors for arterial disease, established arterial disease, and obesity. Factors in the former category included metabolic syndrome, hypertension, and smoking status, while factors in the arterial disease included descending aortic aneurysm, mural thrombi, aortic aneurysm without a dissection, and aortic disease in general. In relation to anterior spinal artery not being detectable, significant risk factors included hypertension, smoking status, and metabolic syndrome, while those associated with arterial disease involved aortic disease and arterial thrombi. When evaluating the importance of individual clinical factors, the presence of higher body mass index was the single most important risk factor. CONCLUSION: Arterial disease, established arterial disease, and increased body mass index are risk factors in the detection of Adamkiewicz artery and anterior spinal artery. Specific diagnostic protocols should be in place for patients with these underlying conditions, thus enhancing the likelihood of detection when the Adamkiewicz artery is indeed present.

Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector Row Computed Tomography Device.

BACKGROUND: Understanding the difference of Adamkiewicz artery (AKA) presentation in healthy and diseased subjects, and the influence of atherosclerotic factors prevalent in aortic disease patients, are important for aortic disease therapeutic planning. This study used a 320-detector row computed tomography (CT) device to examine the impact of clinical aspects of AKA identification in individuals with and without aortic disease. METHODS: Angio-CTs obtained from 115 patients were assessed and the individuals grouped according to the presence or absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA was identified by three-dimensional multiplanar reconstruction. RESULTS: The group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women, with a mean age of 53.7 ± 16.8 years. The group with aortic disease (Group B) comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 ± 11.6 years. AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%) individuals of Group B (P ≤ 0.0001). In 53 cases (73.6%), AKA originated on the left side. AKA was mainly detected on the left side (73.6%), at the level of T10 to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had increased odds of having undetected AKA. CONCLUSIONS: Using the method described and a state of the art 320-detector row CT device, AKA was detected more frequently among individuals without aortic disease. Thus, aortic disease and atherosclerotic risk factors hindered AKA detection.

Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

BACKGROUND: Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. METHODS: Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts. RESULTS: Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments. CONCLUSIONS: LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach to coronary allograft vasculopathy.

Anatomia da circulação medular / Anatomy of spinal blood supply

A intrincada anatomia tridimensional da irrigação medular é frequentemente explanada na literatura com diferentes nomenclaturas e devido a sua alta relevância no estudo da isquemia medular, o estudo da terminologia se faz necessário para melhor compreensão do tema. A artéria de Adamkiewicz, também chamada de artéria radicular magna, é a via principal. Foi realizada a revisão da literatura com equiparação das nomenclaturas utilizadas e elaboração de descrição acurada e sumarizada do conhecimento atual sobre a vascularização medular.

The intricate three-dimensional vascular anatomy of the spinal cord is still not completely understood, and its terminology varies between studies. In view of its importance in spinal ischemia, an analysis is needed of the anatomic vocabulary used to describe the spinal cord blood supply to improve understanding of the subject. The main supply is the Adamkiewicz artery, also known as great anterior radicular artery. The literature was reviewed to equate the different nomenclatures employed and an accurate description of current knowledge on spinal cord vascularization was prepared.