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1.
Sci Rep ; 13(1): 21375, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049600

RESUMO

Four structured acylglycerols with stigmasterol bonded by a succinyl linker were investigated and their stability were analyzed. Samples were heated to 60 °C and kept at that temperature to simulate storage, and to 180 °C to simulate frying conditions. The degradation of the synthesized compounds and formed derivatives was determined, and their cytotoxicity and genotoxicity on normal human cells from the digestive system was determined. Holding at 180 °C resulted in greater degradation of the compounds than holding at 60 °C. The most stable compound in each sample proved to be one with oleic acid in its structure-1,3-dioleoyl-2-stigmasterylsuccinoyl-sn-glycerol (DO2SSt) at 60 °C and 1,2-dioleoyl-3-stigmasterylsuccinoyl-sn-glycerol (DO3SSt) at 180 °C. These results indicate that the type of fatty acid in the molecule is more important than its position in the glycerol structure. None of the diacylmonostigmasterylsuccinoyl-sn-glycerols (DASStGs) before or after heating exhibited cytotoxic or genotoxic potential to small intestine and colon mucosa cells.


Assuntos
Glicerídeos , Estigmasterol , Humanos , Glicerídeos/toxicidade , Glicerol/química , Calefação , Ácidos Graxos
2.
Food Chem ; 421: 136194, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37094401

RESUMO

The safety and thermoxidative stability of new diacyl-stigmasterylcarbonoyl-sn-glycerols (DAStGs) with two molecules of palmitic or oleic acids and one molecule of stigmasterol at the sn-2 or sn-3 position were studied. After heating to 60 °C, the compounds with stigmasterol at the sn-2 position were more stable than those with stigmasterol at the sn-3 position. The lowest level of degradation of stigmasterol after heating to 180 °C was detected for both compounds with oleic acid, followed by the samples with palmitic acid. The high content of SOPs, especially triolSt, as well as the high level of dimers showed the most effect on the cytotoxicity of DAStGs heated at both temperatures. DAStGs with oleic acid at sn-1,3 and stigmasterol at sn-2 position were the most stable compounds. Both oleic acid and the location of stigmasterol in the middle of the glycerol molecule play an important role in increasing the thermoxidative stability of stigmasterol.


Assuntos
Ácidos Graxos , Glicerídeos , Estigmasterol , Ácido Oleico/farmacologia , Glicerol , Estresse Oxidativo
3.
Food Chem ; 390: 133150, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35551028

RESUMO

The study investigated the thermo-oxidative stability of distigmasterol-modified acylglycerols as a new structured acylglycerols. Samples were heated at 60 and 180 °C for 8 h. Their percentage degradation and products formed during heating were compared with free stigmasterol and stigmasteryl esters. The remaining of stigmasterol and fatty acid parts, the formation of stigmasterol oxidation products and the composition of polar and non-polar fractions were analysed using chromatographic methods. The cytotoxicity and genotoxicity were determined with the use of an MTT test and a comet assay, respectively. The highest stability during heating was observed for 2,3-distigmasterylsuccinoyl-1-oleoyl-sn-glycerol (dStigS-OA) and the lowest for 2,3-distigmasterylcarbonoyl-1-oleoyl-sn-glycerol (dStigC-OA). Data showed that the formation of thermo-oxidative degradation products is affected by the temperature and chemical structure of lipids present in the molecule. The dStigMAs bonded by a succinate linker and products formed during their thermo-oxidation showed no cytotoxic or genotoxic activity to normal human cells.


Assuntos
Fitosteróis , Glicerídeos , Glicerol , Humanos , Estresse Oxidativo , Fitosteróis/química , Estigmasterol/química
4.
J Am Oil Chem Soc ; 90(7): 933-939, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23805002

RESUMO

A method utilizing thin-layer chromatography with a flame ionization detector (TLC-FID) was developed for assessing the stability of breeder's oil seed samples based on the formation of polar compounds. The results showed a linear relationship between peroxide value (PV) and the content of polar material in the oxidized oil. Oil samples oxidized very readily on chromarods, even at low temperature, which is a particular advantage for antioxidant screening. At 45 °C, the oil oxidation rate was relatively low, but the relationship between the content of polar material and reaction time was linear. At 65 °C, if the content of polar material was below 50 %, the above relationship was still linear. At different temperatures, the action of tocopherol appeared to vary slightly. For example, at 65 °C, the oxidative stability of the oil sample was determined by the content of tocopherol, especially γ-tocopherol. At 45 and 55 °C, the oxidative stability was determined by both the content of tocopherol and polyunsaturated fatty acids. Of the tocopherol isomers, γ-tocopherol exhibited the highest antioxidant potency, consistent with the published literature. These results suggest that chromarods provide good media for monitoring oil oxidation for antioxidant screening. A particular advantage is the use of very small oil samples, usually 1-2 µL, and the ability to analyze multiple samples at the same time.

5.
Nutr Metab Cardiovasc Dis ; 20(9): 641-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19836216

RESUMO

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with the etiology and pathogenesis of heart disease including congestive heart failure. We previously observed cardiac hypertrophy in vitamin D deficient rats and vitamin D receptor knockout mice. These studies indicate that the absence of vitamin D-mediated signal transduction and genomic activation results in increased sensitivity of the heart to ionotropic stimuli and cardiomyocyte hypertrophy. This study's aim is to investigate the relationship between vitamin D status and the heart failure phenotype in the rat. METHODS AND RESULTS: Vitamin D status was assessed by measuring 25-hydroxyvitamin D levels and related to heart weight in young, middle-aged and aging spontaneously hypertensive, heart failure (SHHF) prone rats. We also measured the effects of the vitamin D hormone,1,25(OH)(2)D(3), on cardiac function in SHHF rats. Cardiac hypertrophy in this model of the failing heart increased with age and related to decreasing vitamin D status. Vitamin D deficiency presented after cardiac hypertrophy was first observed. Additionally, we found that 1,25(OH)(2)D(3) treatment between 4.0 and 7.0 months of age prevented cardiac hypertrophy and permits decreased workload for the heart while allowing adequate blood perfusion and pressure, resulting in reduced cardiac index. CONCLUSIONS: Our findings suggest that low vitamin D status is associated with the progression and final terminal phase of the heart failure phenotype and not with initial heart hypertrophy. Also, we report that in the vitamin D sufficient SHHF rat, 1,25(OH)(2)D(3) treatment provided protection against the progression of the heart failure phenotype.


Assuntos
Insuficiência Cardíaca/complicações , Hipertensão/complicações , Deficiência de Vitamina D/complicações , Animais , Calcifediol/sangue , Calcitriol/uso terapêutico , Cardiomegalia/complicações , Cardiomegalia/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Obesidade/sangue , Obesidade/complicações , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Cloreto de Sódio na Dieta/administração & dosagem
6.
Transplant Proc ; 41(8): 3171-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19857704

RESUMO

BACKGROUND: Antiapoptotic as well as replacement and proliferative mechanisms take place in the myocardium in dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). We sought to estimate antiapoptotic, proliferative and replacement activities in cardiomyopathies. MATERIALS: The study groups included seven hearts with DCM and eight with IHD, which had been explanted at the time of transplantation. The comparator group consisted of cases of myocardial hypertrophy and the control group, donor fragments. METHODS: Antiapoptotic and proliferative responses were determined immunohistochemically as Bcl-2 and Ki67 expression by semiquantitative assessment of the intensity of staining. We also measured and statistically analyzed the integrative morphometric measurements of the fraction of fibrosis area, the nucleosarcoplasmic ratio, and cardiocyte diameter. RESULTS: No Bcl-2 expression was observed in the controls. The strongest reaction was seen in the DCM group, then in the IHD, and in the comparator group of myocardial hypertrophy. Proliferative activity was seen only in endocardial and interstitial fibroblasts in DCM and IHD cases. The cardiocyte diameter showed no statistical association between myocardial hypertrophy and IHD, or IHD and DCM, whereas the nucleosarcoplasmic ratios were significantly different from control groups for all comparisons. Myocardial fibrosis showed the highest values in DCM and IHD. Discriminant analysis showed the value of interstitial fibrosis and cardiocyte diameter to categorize the analyzed groups. CONCLUSIONS: Antiapoptotic Bcl-2 activity seemed to play an important role in cardiocyte preservation, while proliferative activity was resticted to interstitial connective tissue cells as a replacement process. Myocardial Bcl-2 expression, the extent of myocardial fibrosis, and cardiocyte diameter may serve as additional diagnostic tools to differentiate cardiomyopathies.


Assuntos
Cardiomegalia/patologia , Cardiomiopatia Dilatada/patologia , Transplante de Coração/patologia , Isquemia Miocárdica/patologia , Adulto , Apoptose , Divisão Celular , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto Jovem
7.
Transplant Proc ; 41(8): 3179-84, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19857705

RESUMO

BACKGROUND: Morphometric studies based on the measurement of cardiocyte nuclei have focused on progressive hypertrophy rather than shape, which is a deciding factor for the diagnosis of hypertrophy in myocardial diseases. The aim of this research was to demonstrate how the digital morphology of cardiocyte nuclei change correlated with the type of myocardial pathology. MATERIALS AND METHODS: The study groups encompassed 7 hearts with dilated cardiomyopathy (DCM) and 8 hearts with ischemic heart disease (IHD) which were explanted. A comparative group consisting of myocardial hypertrophy was contrasted with a control group of donor heart fragments. Cardiocyte nuclei were evaluated morphometrically on histologic slides. We calculated the nuclear area, length, breadth, perimeter, roundness, elongation, fullness factors, and nuclear chromatin mean gray level. The results were subjected to discriminant analysis. RESULTS: All karyometric measurements analyzed by backward discriminant analysis showed only 2 powerful factors: nuclear breadth and chromatin mean gray level. The Mahalanobis distance showed the proximity of control and hypertrophy groups, whereas differences between IHD and DCM were nonsignificant. CONCLUSION: The lack of karyometric differences between IHD and DCM suggested a common morphologic response for long-lasting progressive injury. The main morphologic differences were dependent on nuclear chromatin activity/stainability and nuclear breadth, suggesting darker and thinned nuclei in normal and adaptative stages and irregular brighter nuclei in cardiomyopathies.


Assuntos
Cardiomiopatias/patologia , Transplante de Coração/patologia , Cariometria/métodos , Cardiomegalia/patologia , Núcleo Celular/patologia , Análise Discriminante , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Isquemia Miocárdica/cirurgia , Miócitos Cardíacos/patologia , Valores de Referência , Disfunção Ventricular Esquerda/patologia , Adulto Jovem
8.
Transplant Proc ; 41(8): 3202-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19857710

RESUMO

OBJECTIVE: Acute cellular rejection in heart transplants is characterized by an active lymphocytic infiltration, whereas the humoral response shows complement deposits in myocardial tissue. Both reactions may produce hemodynamic compromise during the first months after orthotopic heart transplantation (OHT). The aim of this study was to estimate the coexistence of humoral rejection symptoms in the first posttransplant biopsy with mild/moderate cellular rejection as an additional prognostic factor. MATERIALS AND METHODS: The study group included 13 biopsies obtained from 11 men and 2 women of overall mean age of 52.6 +/- 5.3 years who displayed International Society for Heart and Lung Transplantation (ISHLT) mild/moderate rejection grades. The control group consisted of 11 biopsies obtained from 8 men and 3 women of overall mean age of 54.8 +/- 3.6 years with no signs of rejection. Complement deposits were determined immunohistochemically using anti-C4d antibodies (Quidel Corporation). RESULTS: None of the control cases showed a positive reaction, whereas 3 men in the study group of mean age of 56.1 +/- 5.8 years revealed regional positive anti-C4d expression with cellular infiltrates. This expression occurred in all myocardial components adjacent to lymphocytic infiltrations. The survival rates were comparable in both the pure cellular versus the mixed rejection groups. The relative rate of grade 3 rejection in the posttransplantation period was increased among patients with mixed types of rejection. CONCLUSIONS: The term "mixed acute rejection" should be applied to cases with coincidence of 2 forms of acute rejection. It seemed to be associated with more frequent grade 3 rejection processes upon long-term follow-up.


Assuntos
Cardiomiopatia Dilatada/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Adulto , Biópsia , Cardiomiopatia Dilatada/cirurgia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Transplante de Coração/patologia , Humanos , Imunidade Celular , Imunidade Humoral , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/cirurgia
9.
Transplant Proc ; 41(8): 3219-21, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19857714

RESUMO

BACKGROUND: Clinical studies with intravascular ultrasound have suggested that even subclinical cytomegalovirus (CMV) infections increase intimal hyperplasia in transplanted heart coronary arteries after 1 year. The potential influence of CMV on microvasculopathy development is not known. The Aim of our study was to compare the occurrence of microvasulopathy in endomyocardial biopsies (EMBs) of heart transplant recipients with versus without CMV infection. MATERIALS AND METHODS: We performed a case-controlled, retrospective study of 58 subjects diagnosed with CMV infection by the presence of pp65 antigen. The 49 men and 91 women of overall age 49 +/- 8 years showed ischemic cardiomyopathy in 52%. We matched a control cohort of 58 subjects without CMV disease. Microvasculopathy was assessed using 4-degree grading system developed by Hiemann et al for elective EMBs performed at 1 and 12 months after transplantation. RESULTS: Significant acute rejection episodes were observed among 22% versus 21% of 1-month EMBs, and 3% versus 5% of 12-month EMBs for CMV(+) versus control group subjects respectively. The commonest microvasculopathy was nonstenotic thickening (grade B) 60% versus 59% (35 versus 34 patients) among 1-month EMBs; and 50% versus 60% (29 vs 35 patients) among 12-month EMBs, respectively. Progression of microvasculopathy score between 1- and 12-month EMB was observed in 40% versus 41% of subjects, and regression occurred in 22% versus 21%, respectively. None of differences was significant. CONCLUSION: Our data do not support the thesis that CMV infection promotes microvasculopathy development among heart transplant recipients.


Assuntos
Infecções por Citomegalovirus/fisiopatologia , Transplante de Coração/efeitos adversos , Doenças Vasculares/fisiopatologia , Adulto , Antígenos Virais/sangue , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/patologia , Progressão da Doença , Endotélio Vascular/patologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Transplante de Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia
10.
Transplant Proc ; 41(1): 281-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19249535

RESUMO

INTRODUCTION: Cardiocyte hypertrophy is accompanied by polyploidy, seen as a decrease in chromatin density in the enlarged nucleus. Repeated biopsies of a transplanted heart offer the possibility of a dynamic evaluation of these phenomena. The aim of this work was an evaluation of cardiocyte nuclear chromatin density in transplanted hearts during long-term follow-up. MATERIALS AND METHODS: The material encompassed myocardial biopsy specimens taken during the first week, first month, and then on an annual basis up to 10 years after surgery. Only biopsy specimens with no rejection were considered (grade "0" International Society for Heart and Lung Transplantation [ISHLT] 122 biopsy specimens). The control group consisted of 7 donor heart specimens. We evaluated the optical density-mean gray level-of cardiomyocyte nuclear chromatin. We determined correlations of this index with the nuclear area, and with left ventricle ultrasound measurements, using correlation analysis. RESULTS: The chromatin mean gray level decreased with time, correlating positively with interventricular septum thickness, left ventricle posterior wall diameter, and left ventricular mass. Analysis of individual periods showed a significant positive correlation of the mean grey level with the cardiocyte nuclear surface in year 3, 4, and 9 after transplantation, thereby suggesting the occurrence of polyploidy at those times. The significant negative correlation of these values (1 week and 1 year) indicated normalization of early cardiocyte hypertrophy. CONCLUSIONS: With the passage of time chromatin condenses, leading to pyknosis. The activity of cardiocyte chromatin correlated with left ventricular hypertrophy. Compensatory cardiomyocyte polyploidy is a periodical phenomenon.


Assuntos
Cromatina/ultraestrutura , Transplante de Coração/fisiologia , Ventrículos do Coração/anatomia & histologia , Miócitos Cardíacos/citologia , Núcleo Celular/patologia , Ecocardiografia , Seguimentos , Genoma , Septos Cardíacos/patologia , Transplante de Coração/patologia , Ventrículos do Coração/patologia , Humanos , Poliploidia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de Tempo
11.
Transplant Proc ; 39(9): 2825-32, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18021995

RESUMO

UNLABELLED: The aim of this study was to assess the effects of early thymoglobulin administration on cardiocyte nuclear status in orthotopic heart transplant (OHT) recipients. MATERIAL AND METHODS: We investigated endomyocardial biopsies (EMBs) from 31 OHT recipients and 10 control cases. OHT patients were divided into the standard group who were treated without thymoglobuline; an ATG group who received thymoglobulin electively, and a standard+ATG group who were administered thymoglobulin upon a drop in renal function. We evaluated only EMBs obtained at 1 and 4 weeks after OHT showing no significant rejection (ISHLT grades 0 to 1B). The morphometric studies were performed using a computerized, automated Quantimet image analysis system. Overall, 1750 cardiocyte nuclei were quantitated for area, length, breadth, perimeter, chromatin median grey level, and fullness factor. Statistical analysis was performed using the Mann- Whitney U test, the Wilcoxon test, and discriminant analysis. RESULTS: All OHT groups showed significantly higher values (indicating nucleus enlargement) than the control group. All factors suggesting myocardial hypertrophy were significantly higher in the standard group; however, they decreased significantly with time. In contrast, the nuclear geometric parameters were significantly lower and stable throughout the study in the ATG group. The results of the standard+ATG group were intermediate, and their normalization as incomplete at the week 4 examination. Discriminant analysis revealed the closest Mahalanobis distance between control and ATG groups both at and weeks 1 and 4 after OHT. CONCLUSION: Thymoglobulin administered early after surgery protected cardiocyte hypertrophy in heart transplant recipients, mitigating graft ischemic damage.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Cardiomegalia/prevenção & controle , Transplante de Coração/imunologia , Complicações Pós-Operatórias/prevenção & controle , Soro Antilinfocitário , Biópsia , Cardiomegalia/patologia , Transplante de Coração/efeitos adversos , Transplante de Coração/patologia , Humanos , Imunossupressores/uso terapêutico , Miocárdio/patologia , Período Pós-Operatório
12.
Transplant Proc ; 39(9): 2833-40, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18021996

RESUMO

UNLABELLED: Remodeling taking place in transplanted myocardium leads to a change in the number of cardiocytes. Ultrasound measurements and biopsy evaluation should reflect their loss and compensation. We sought to evaluate the morphology of the transplanted heart upon long-term follow-up. MATERIAL AND METHODS: Myocardial biopsies were obtained in the first week, first month, and then annually for 10 years from transplantation that did not show rejection (grade "0" ISHLT, 122 biopsies). The control group encompassed 7 donor heart fragments. Proliferation in biopsies was evaluated with Ki67 (M7240, DAKO), cardiocyte hypertrophy by measuring their diameter, the surface area of the nuclei, nuclear-sarcoplasmic index, and stromal fibrosis evaluated as the surface area fraction. Ultrasound measurements included diastolic thickness of the interventricular septum, posterior wall of the left ventricle, and left ventricular mass. The correlation of measurements with time from transplantation was evaluated using Spearman's test. RESULTS: A positive Ki67 reaction was observed in fibroblasts and endothelial cells. The increased cardiocyte nuclear area correlated with the time elapsed since transplantation (r = 0.2; P < .05) with a simultaneous decrease in cardiocyte thickness (r = -0.3; P < .05), without changes in the nuclear-cytoplasmic index (r = 0.02; P > .05). Stromal fibrosis also increased (r = 0.1; P < .05). Ultrasound measurements of the left ventricle showed a decreased tendency with the passage of time (r = -0.2 to -0.3; P < .05). CONCLUSION: A transplanted heart does not undergo hypertrophy but rather fibrous atrophy with apparent compensatory hypertrophy of the cardiomyocytes.


Assuntos
Transplante de Coração/patologia , Miocárdio/patologia , Remodelação Ventricular/fisiologia , Biópsia , Divisão Celular , Núcleo Celular/ultraestrutura , Diástole , Seguimentos , Sobrevivência de Enxerto , Transplante de Coração/imunologia , Humanos , Imunossupressores/uso terapêutico , Miocárdio/imunologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/patologia , Estudos Retrospectivos , Retículo Sarcoplasmático/ultraestrutura , Fatores de Tempo , Função Ventricular
13.
Transplant Proc ; 39(9): 2841-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18021997

RESUMO

BACKGROUND: Apoptotic mechanisms take place in cardiocyte death during acute heart graft rejection and remodeling by the mitochondrial pathway. This process is suppressed by Bcl-2 protein. Besides that, knowledge about cardiocyte antiapoptotic responses after heart transplantation is scanty. We sought to estimate Bcl-2 expression in the absence of rejection. MATERIAL: The study group included endomyocardial biopsies taken at 1 week, 1 month, 1 through to 10 years after heart transplant, which showed rejection grade "0"; the control group were donor heart fragments. METHOD: Bcl-2 expression was determined immunohistochemically by NP030 antibody (DAKO) and Envision-DAB. The intensity of staining was assessed semiquantitatively. RESULTS: No Bcl-2 expression was seen in the controls; in the posttransplant groups, the significantly strongest sarcoplasmic reaction was observed at 1 week after heart transplant. Thereafter, the reaction decreased, and was weakest in the 3- and 5-year groups. From this time, Bcl-2 expression increased albeit without statistical significance. The intensity of the reaction showed no correlation with the time elapsed from heart transplant (Spearman r = 0.05; P > .05). CONCLUSION: The expression of antiapoptotic Bcl-2 protein occurs during the entire posttransplant period, being probably a preservative and adaptative response.


Assuntos
Transplante de Coração/fisiologia , Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Biópsia , Seguimentos , Sobrevivência de Enxerto/fisiologia , Transplante de Coração/patologia , Humanos , Imuno-Histoquímica , Miocárdio/citologia , Miócitos Cardíacos/citologia , Período Pós-Operatório , Estudos Retrospectivos
14.
Transplant Proc ; 39(9): 2846-9, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18021998

RESUMO

UNLABELLED: Morphometric publications based on the measurement of cardiocyte nuclei indicated their progressive hypertrophy ignoring, however, their shape, which is a deciding factor for the microscopic-based diagnosis of hypertrophy. We sought was to demonstrate how the shapes of cardiocyte nuclei change over time and correlate them with the thickness of the interventricular septum, (IVS) the biopsy site. MATERIAL: We evaluated myocardial biopsies taken in the first week, first month, and then annually until posttransplant year 10. Only biopsies with no rejection were considered: grade "0" ISHLT (122 biopsies). The control group encompassed fragments from seven donor hearts. METHODS: Cardiomyocyte nuclei were evaluated morphometrically. We calculated the length, breadth, perimeter, roundness, elongation, and fullness factors for correlation with the IVS thickness, and selected indices. The relationships between karyometry and IVS thickness (measured by ultrasound) as well as time were calculated by Spearman's correlation test. RESULTS: Among the examined indices, only nuclear length did not correlate significantly with follow-up time. Among the remaining indices, the strongest correlations with time were observed with regard to breadth (r = 0.214), perimeter (r = 0.150), roundness (r = -0.06) and fullness (r = 0.06), and finally elongation (r = 0.02). The decreasing thickness of the interventricular septum (r = -0.31) showed a weak correlation only with the cardiocyte nuclear length (r = -0.05). CONCLUSION: Graft aging imitates hypertrophy inasmuch as cardiocyte nuclei become wider despite the decreased thickness of the interventricular septum. Therefore, karyometric measurements do not reflect myocardial morphology.


Assuntos
Núcleo Celular/ultraestrutura , Transplante de Coração/fisiologia , Miócitos Cardíacos/citologia , Apoptose , Biópsia , Núcleo Celular/patologia , Seguimentos , Septos Cardíacos/citologia , Septos Cardíacos/patologia , Transplante de Coração/patologia , Humanos , Miocárdio/citologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo
15.
Transplant Proc ; 39(9): 2850-2, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18021999

RESUMO

PURPOSE: We performed a short-term outcome analysis of orthotopic heart transplantation (OHT) in patients with pulmonary hypertension (PH) treated perioperatively with oral sildenafil. METHODS: PH (pulmonary vascular resistance > 2.5 Wood units, and/or transpulmonary gradient > 12 mmHg) was diagnosed in 6 of 25 (group A) heart transplant recipients operated in 2006. This group of patients underwent a modified medication protocol including perioperative administration of oral sildenafil: 50 mg before followed by 50 or 25 mg TID after heart transplantation. Sildenafil treatment was discontinued 10 to 14 days post OHT, after stepwise dose reduction. During the ICU stay all patients underwent circulatory monitoring of pulmonary and systemic pressures and resistance as well as transthoracic echocardiogram (TTE) evaluation. RESULTS: Perioperative oral sildenafil administration in PH patients undergoing OHT was associated with good short-term outcomes in the majority of transplanted patients (4/6). Sildenafil treatment reduced pulmonary resistance and pressures with a low rate of hemodynamic instability among OHT patients. CONCLUSIONS: Pharmacologic perioperative reduction of PH improves the short-term prognosis for successful OHT. One may speculate whether sildenafil treatment transplant recipients with PH would be associated with long-term improvement of pulmonary vascular status, therefore leading to extended life-expectancy and improved outcomes.


Assuntos
Insuficiência Cardíaca/prevenção & controle , Transplante de Coração/efeitos adversos , Hipertensão Pulmonar/tratamento farmacológico , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Débito Cardíaco/efeitos dos fármacos , Esquema de Medicação , Ecocardiografia Transesofagiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Circulação Pulmonar/efeitos dos fármacos , Purinas/uso terapêutico , Citrato de Sildenafila , Resistência Vascular/efeitos dos fármacos
16.
Transplant Proc ; 39(9): 2853-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022000

RESUMO

INTRODUCTION: The aim of this study was to assess nephroprotective influence of intravenous N-acetylcysteine (NAC) on renal function after radiocontrast use in calcineurin inhibitor-treated patients after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We analyzed the results of 112 consecutive coronary angiography examinations (CAG). All patients received intravenous 500 mL multielectrolyte fluid (PWE) before catheterization. Group I of 55 randomly selected cases in addition were treated with 300 mg of NAC. The other 57 cases (group II) received only hydration. After catheterization, we administered 500 mL 0.9% saline with 20 mg furosemide. A nonionic, low-osmolality contrast agent (OPTIRAY) was used for all catheterizations. All patients underwent measurements of serum creatinine and creatinine clearance levels before and after the procedure (CREA0, CREA1, CC0, and CC1, respectively). We assessed the influence of NAC on CREA1 and the relative change of CREA1/CREA0 and CC1/CC0 ratios. RESULTS: In groups I and II we noticed decreased CC0 in 17 versus 22 cases (31% vs 39%), a relative change of CREA1/CREA0 ratio of 0% versus -3.95% and of CC1/CC0 ratio 0% versus 4, 11%, respectively. CIN was not recognized in any patient. None of the differences was significant. CONCLUSION: Intravenous NAC (300 mg) along with hydration before radiocontrast use had no impact on renal function in OHT patients undergoing CAG. It seems that there is no need for an additional preventive strategy apart from hydration and a small volume of low osmolar contrast in the majority of patients.


Assuntos
Acetilcisteína/uso terapêutico , Cateterismo Cardíaco , Meios de Contraste/efeitos adversos , Angiografia Coronária , Transplante de Coração/fisiologia , Adulto , Idoso , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/prevenção & controle , Creatinina/sangue , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
17.
Transplant Proc ; 39(9): 2856-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022001

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a predictor of early death risk owing to right heart insufficiency after orthotopic heart transplantation (OHT). The aim of this study was to evaluate the effectiveness and safety of sildenafil therapy to decrease pulmonary vascular resistance (PVR) in patients with heart failure requiring transplantation, who may otherwise have been excluded because of PH. MATERIAL AND METHODS: We analyzed the hemodynamic results of six men (aged 47 to 61) with well-grounded OHT indications and PH diagnosed by a transpulmonary gradient (TPG) > 12 mmHg and/or PVR > 2.5 Wood units. Patients underwent a PH reversibility test with sodium nitroprusside (NPS) to achieve normal TPG and PVR results without a drop in systolic arterial pressure <85 mmHg. Unresponsiveness to NPS was shown in all subjects, who were subsequently qualified for sildenafil therapy (50 mg bid). RESULTS: After 1 month of sildenafil, three subjects achieved normal TPG and PVR, and acceptable responsiveness of PH to NPS in two other patients, all of whom qualified for OHT. Therapy was unsuccessful in one patient, which was confirmed also by right heart catheterization after 3 months of sildenafil use. Therapy was well tolerated in all patients, namely, no significant drop in arterial pressure on angiotensin-converting enzyme inhibitors. CONCLUSIONS: Sildenafil may be effectively used for treatment of secondary, irreversible PH in potential heart transplant recipients.


Assuntos
Transplante de Coração/fisiologia , Hipertensão Pulmonar/tratamento farmacológico , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Vasodilatadores/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Circulação Pulmonar/efeitos dos fármacos , Purinas/uso terapêutico , Segurança , Citrato de Sildenafila , Resistência Vascular/efeitos dos fármacos
18.
Transplant Proc ; 39(9): 2859-61, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022002

RESUMO

UNLABELLED: The aim of the study was to compare long-term results of intracoronary implantation of drug-eluting stents (DES) and bare metal stents (BMS) in patients suffering from transplant coronary artery disease (TxCAD). MATERIAL AND METHODS: We performed a retrospective analysis of all intracoronary stent implantations for TxCAD among subjects with at least one follow-up coronary angiography. We identified 28 sirolimus-eluting DES (n = 17) patients, 24 BMS (n = 13 patients), and both DES and BMS (n = 7 patients) implantations among 23 recipients. Mean follow-up after DES was 14 months and after BMS implantation, 20 months. We compared the occurrence of in-stent restenosis (ISR), and patient survival in the context of risk factors that were identified separately for each stent type. Significance was assessed using the log-rank, chi(2) and Mann-Whitney U test. RESULTS: There were 2 (7%) ISR among DES versus 14 (58%) ISR among BMS (P = .0002) patients, with a longer time of freedom from IRS after DES implantation (P = .022). There were three deaths (18%) among DES, four (31%) with BMS, and one (14%) with DES and BMS (P = NS). Left anterior descending artery was the place of DES implantation in 17 (61%) versus 10 (42%) of BMS cases (P = NS). Risk factor profile was comparable except for a higher age at the time of transplantation (46 +/- 7 vs 41 +/- 6 years; P = .011) and stent implantation (54 +/- 7 vs 49 +/- 6 years; P = .0002) for DES. CONCLUSION: Favorable long-term results of sirolimus-eluting stents over BMS implanted for TxCAD suggested their preferential use in heart transplant recipients.


Assuntos
Doença das Coronárias/cirurgia , Stents Farmacológicos , Transplante de Coração/efeitos adversos , Sirolimo/uso terapêutico , Stents , Angiografia Coronária , Doença das Coronárias/mortalidade , Reestenose Coronária/prevenção & controle , Transplante de Coração/mortalidade , Humanos , Imunossupressores/uso terapêutico , Metais , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
Transplant Proc ; 39(9): 2862-5, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022003

RESUMO

UNLABELLED: Our aim was to assess the medium-time results after orthotopic heart transplantation (OHT) depending on the serostatus of heart transplant recipients at the time of transplantation. MATERIALS AND METHODS: We enrolled 120 patients in this retrospective study including 107 males and an overall mean age of 49.1 +/- 8.6 years ischemic heart disease (IHD) was the diagnosis before OHT in 46%. The mean follow-up was 48 months. The first diagnostic coronary angiography was routinely preformed at 1 year after OHT, and then every second year. We evaluated every incidence of a change in the coronary arteries, the presence of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, death, or retransplantation. Using indirect immunofluorescence assays we detected Epstein-Barr virus (EBV) antigenemia by identification of antibodies against early antigens of EBV (EA) of IgM and IgG classes as well as IgG antibodies against nuclear antigen of EBV (EBNA). Since April 2001 all three types of antibodies were routinely investigated on admission to the hospital for OHT. RESULTS: At the time of transplantation, IgM-EA antibodies were detected in 17 (14%) patients, IgG-EA in 35 (29%), and IgG-EBNA in 113 (94%). Survival rate, incidence of cardiac allograft vasculopathy and death, as a function of the serostatus of the heart recipient at the time of transplantation were estimated by Kaplan-Meier curves; the results were compared by log-rank tests. The findings among IgM EA, IgG EA, and IgG EBNA-positive and -negative groups were statistically comparable. CONCLUSION: Infection with EBV before OHT did not worsen the prognosis over the first 4 years after transplantation.


Assuntos
Antígenos Virais/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Transplante de Coração/efeitos adversos , Adulto , Vasos Coronários/patologia , Vasos Coronários/virologia , Infecções por Vírus Epstein-Barr/sangue , Feminino , Seguimentos , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Sobreviventes , Fatores de Tempo
20.
Transplant Proc ; 39(9): 2866-9, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022004

RESUMO

AIM: We sought to determine the impact of cytomegalovirus (CMV) infection on cardiac allograft vasculopathy (CAV) development in the long term after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We enrolled 144 patients in this retrospective study including 128 men with an overall age at transplantation of 48.4 +/- 9.3 years. Before OHT, 45% exhibited ischemic heart disease (IHD). The mean follow-up was 62 months. Detection of CMV antigenemia was performed by identification of pp65-antigen on peripheral blood leukocytes. The first diagnostic coronary angiography was routinely performed at 1 year after heart transplantation and thence every second year. We evaluated every incidence of change in the coronary arteries, of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, of death or of transplantation. All patients were followed to the incidence of a cardiovascular event, death, or the end of observation. RESULTS: Of 144 patients, 33 were pp65 positive, namely 29 men with overall mean age at transplantation of 48 +/- 10.3 years. Before OHT, 52% had IHD. The incidence of CAV during follow-up was 24% (n = 8) in the pp65(+) and 22% (n = 24) in the pp65(-) group. It was significant in 3 (9%) versus 8 (24%) patients. There were 4 (12%) deaths in pp65(+) and 9 (8%) deaths in the pp65(-) groups. Kaplan-Meier survival curves to estimate the time for CAV development and death showed no significant differences by log-rank tests. CONCLUSION: No impact of CMV infection on CAV development was observed in first 5 years after OHT.


Assuntos
Infecções por Citomegalovirus/complicações , Transplante de Coração/efeitos adversos , Fosfoproteínas/sangue , Proteínas da Matriz Viral/sangue , Adulto , Doença das Coronárias/epidemiologia , Vasos Coronários/patologia , Infecções por Citomegalovirus/sangue , Feminino , Seguimentos , Sobrevivência de Enxerto/fisiologia , Transplante de Coração/mortalidade , Transplante de Coração/fisiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Análise de Sobrevida , Sobreviventes , Fatores de Tempo , Transplante Homólogo
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