RESUMO
FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.
Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Masculino , Camundongos , Animais , Feminino , Regulação para Cima , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Desenvolvimento Embrionário , RNA/metabolismo , Diferenciação Celular , Adenosina/metabolismo , Envelhecimento/genéticaRESUMO
Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Ponte de Artéria Coronária , Doença da Artéria Coronariana , Marcadores Genéticos , RNA Longo não Codificante/genética , Doença da Artéria Coronariana/genética , República Tcheca , Genótipo , Humanos , Polimorfismo GenéticoRESUMO
Autologous and allogenic human pericardia used as biomaterials for cardiovascular surgery are traditionally crosslinked with glutaraldehyde. In this work, we have evaluated the resistivity to collagenase digestion and the cytotoxicity of human pericardium crosslinked with various concentrations of glutaraldehyde in comparison with pericardium crosslinked by genipin, nordihydroguaiaretic acid, tannic acid, and in comparison with unmodified pericardium. Crosslinking retained the wavy-like morphology of native pericardium visualized by second harmonic generation microscopy. The collagenase digestion products were analyzed using SDS-PAGE, capillary electrophoresis, and a hydroxyproline assay. Glutaraldehyde and genipin crosslinking protected the native pericardium efficiently against digestion with collagenase III. Only low protection was provided by the other crosslinking agents. The cytotoxicity of crosslinked pericardium was evaluated using xCELLigence by monitoring the viability of porcine valve interstitial cells cultured in eluates from crosslinked pericardium. The highest cell index, reflecting both the number and the shape of the monitored cells was observed in eluates from genipin. Crosslinking pericardium grafts with genipin therefore seems to be a promising alternative procedure to the traditional crosslinking with glutaraldehyde, because it provides similarly high protection against degradation with collagenase, without cytotoxic effects.
Assuntos
Reagentes de Ligações Cruzadas , Pericárdio/química , Transplantes/química , Materiais Biocompatíveis , Glutaral , Humanos , Iridoides , Masoprocol , TaninosRESUMO
An important complication of the prolonged left ventricle assist device support in patients with heart failure is unloading-induced cardiac atrophy which proved resistant to various treatments. Heterotopic heart transplantation (HTx) is the usual experimental model to study this process. We showed previously that implantation of the newly designed intraventricular spring expander can attenuate the atrophy when examined after HTx in the failing heart (derived from animals with established heart failure). The present study aimed to examine if enhanced isovolumic loading achieved by implantation of the expander would attenuate cardiac post-HTx atrophy also in the healthy heart. Cardiac atrophy was assessed as the ratio of the transplanted-to-native heart weight (HW) and its degree was determined on days 7, 14, 21 and 28 after HTx. The transplantation resulted in 32±3, 46±2, 48±3 and 46±3 % HW loss when measured at the four time points; implantation of the expander had no significant effect on these decreases. We conclude that enhanced isovolumic loading achieved by intraventricular implantation of the expander does not attenuate the development of cardiac atrophy after HTx in the healthy heart. This indicates that such an approach does not represent a useful therapeutic measure to attenuate the development of unloading-induced cardiac atrophy.
Assuntos
Transplante de Coração/instrumentação , Transplante de Coração/métodos , Coração Auxiliar , Miocárdio/patologia , Transplante Heterotópico/instrumentação , Transplante Heterotópico/métodos , Animais , Atrofia/patologia , Atrofia/cirurgia , Coração/diagnóstico por imagem , Masculino , Ratos , Ratos Endogâmicos LewRESUMO
The present experiments were performed to evaluate if increased heart tissue concentration of fatty acids, specifically myristic, palmitic and palmitoleic acids that are believed to promote physiological heart growth, can attenuate the progression of unloading-induced cardiac atrophy in rats with healthy and failing hearts. Heterotopic abdominal heart transplantation (HT(x)) was used as a model for heart unloading. Cardiac atrophy was assessed from the ratio of the native- to-transplanted heart weight (HW). The degree of cardiac atrophy after HT(x) was determined on days 7, 14, 21 and 28 after HT(x) in recipients of either healthy or failing hearts. HT(x) of healthy hearts resulted in 23+/-3, 46+/-3, 48+/-4 and 46+/-4 % HW loss at the four time-points. HT(x) of the failing heart resulted in even greater HW losses, of 46+/-4, 58+/-3, 66+/-2 and 68+/-4 %, respectively (P<0.05). Activation of "fetal gene cardiac program" (e.g. beta myosin heavy chain gene expression) and "genes reflecting cardiac remodeling" (e.g. atrial natriuretic peptide gene expression) after HT(x) was greater in failing than in healthy hearts (P<0.05 each time). Exposure to isocaloric high sugar diet caused significant increases in fatty acid concentrations in healthy and in failing hearts. However, these increases were not associated with any change in the course of cardiac atrophy, similarly in healthy and post-HT(x) failing hearts. We conclude that increasing heart tissue concentrations of the fatty acids allegedly involved in heart growth does not attenuate the unloading-induced cardiac atrophy.
Assuntos
Ácidos Graxos Monoinsaturados/metabolismo , Insuficiência Cardíaca/metabolismo , Transplante de Coração/métodos , Ácido Mirístico/metabolismo , Ácido Palmítico/metabolismo , Transplante Heterotópico/métodos , Animais , Insuficiência Cardíaca/cirurgia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Ratos , Ratos Endogâmicos LewRESUMO
Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation.
Assuntos
Transplante de Coração/efeitos adversos , Traumatismo por Reperfusão Miocárdica/etiologia , Miocárdio/patologia , Doadores de Tecidos , Aloenxertos , Apoptose , Caspase 3/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Necrose , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Troponina T/metabolismoRESUMO
BACKGROUND: Antibody-mediated rejection (AMR) is a serious complication of organ transplantation, and its treatment is complex. The aim of this study was to assess immunoadsorption (IA) for treatment-immunized patients before heart transplantation (HTX) and as the first step of AMR treatment after HTX. METHODS: The cohort consisted of 10 patients (8 men, 2 women; age range, 20-57 years). For 3 of these patients, IA was included in the desensitization protocol before HTX; for 7 patients, IA was the first step of the treatment protocol. One patient underwent IA before and after HTX. RESULTS: A comparison of values before IA and after the last procedure showed a decrease in immunoglobulin subgroups (G, M, and A). In patients before HTX, a decline was noted in panel reactive antibodies. After HTX, IA procedures led to a significant decrease in donor-specific antibody (DSA) class I; DSA class II fell in 6 of 7 patients, with 51% falling below the detection limit. CONCLUSIONS: IA in patients during HTX is safe procedure for reducing DSA. The removal of antibodies is the first step in comprehensive treatment and must be followed by a procedure that prevents their further development.
Assuntos
Transplante de Coração/métodos , Técnicas de Imunoadsorção , Adolescente , Adulto , Anticorpos/imunologia , Dessensibilização Imunológica/métodos , Feminino , Rejeição de Enxerto/imunologia , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Adulto JovemRESUMO
Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4+/-22.9 ng/l, compared to 68.4+/-10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.
Assuntos
Apoptose/fisiologia , Transplante de Coração/efeitos adversos , Miocárdio/metabolismo , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/metabolismo , Doadores de Tecidos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Necrose/diagnóstico , Necrose/metabolismo , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety-six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyopathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68-positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in the perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in the arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group. According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself.
Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Aterosclerose/metabolismo , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Adulto , Idoso , Aterosclerose/diagnóstico , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Doença da Artéria Coronariana/diagnóstico , Feminino , Transplante de Coração/tendências , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ventricular assist devices (VAD) have recently established themselves as an irreplaceable therapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD application. On the other hand, both clinical and experimental studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart atrophy. One aim of this review was to present important aspects of the development of VAD-related cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental models. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising.
Assuntos
Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Animais , Atrofia/etiologia , Atrofia/patologia , Atrofia/terapia , Clembuterol/uso terapêutico , Insuficiência Cardíaca/patologia , HumanosRESUMO
Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations = 2.5 % can be safely recommended.
Assuntos
Ventrículos do Coração/efeitos dos fármacos , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Masculino , Ratos , Ratos Wistar , Sístole , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaRESUMO
The heart transplant program at the Institute for Clinical and Experimental Medicine in Prague was established on January 31, 1984. Through November 2012, 881 orthotopic cardiac transplantations have been performed, with an annual rate of about 40 procedures. Current legislation concerning solid organ transplantations in the Czech Republic is described. Like other centers, we have noticed an increasing age of donors, and, reflecting the shortage of grafts, we have expanded our selection criteria for heart transplantation. The advent of a mechanical circulatory support program at our center in April 2003 has given us another valuable tool in the management of chronic heart failure patients. Currently, around half of our patients are transplanted from mechanical support. Nonischemic etiology of heart failure is a leading cause of transplantation at our center, followed by ischemic cardiomyopathy, valvular heart lesions, and adult congenital heart diseases. Our current immunosupression protocol, including induction therapy, is outlined in detail and survival rates, as well as most common complications and our treatment strategies, are also discussed.
Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/estatística & dados numéricos , Transplante de Coração/tendências , Coração Auxiliar/estatística & dados numéricos , Adolescente , Adulto , Idoso , Aterosclerose/epidemiologia , Criança , Pré-Escolar , República Tcheca/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/terapia , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Coração Auxiliar/tendências , Humanos , Incidência , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Seleção de Pacientes , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/tendências , Transplante Homólogo , Adulto JovemRESUMO
Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22+/-1.73 vs. 3.63+/-2.37 microg/l; P=0.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4+/-10.4 vs. 20.3+/-11.2 microg/l; P=0.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1+/-20.1 vs. 50.6+/-23.2; P=0.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia.
Assuntos
Anestésicos Combinados , Anestésicos Inalatórios , Cardiotônicos/farmacologia , Idoso , Biomarcadores/sangue , Dexmedetomidina , Feminino , Humanos , Ketamina , Masculino , Éteres Metílicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sevoflurano , Sufentanil , Cirurgia TorácicaRESUMO
Cardiac resynchronization therapy is not commonly used in the early postoperative period in patients undergoing cardiac surgery who have left ventricular (LV) dysfunction and a history of heart failure. We performed a prospective randomized clinical trial to compare atrial synchronous right ventricular (DDD RV) and biventricular (DDD BIV) pacing within 72 hours after cardiac surgery in patients with an EF ≤35 %, a QRS interval longer than 120 msec and who had LV dyssynchrony detected by real-time three-dimensional echocardiography (RT3DE). Epicardial pacing was provided by a modified Medtronic INSYNC III pacemaker. An LV epicardial pacing lead was implanted on the latest activated segment of the LV based on RT3DE. The study included 18 patients with ischemic heart disease, with or without valvular heart disease (14 men, 4 women, average age 71 years). Patients undergoing DDD BIV pacing had a statistically significant greater CO and CI (CO 6.7±1.8 l/min, CI 3.4±0.7 l/min/m(2)) than patients undergoing DDD RV pacing (CO 5.5±1.4 l/min, CI 2.8±0.7 l/min/m(2)), p<0.001. DDD BIV pacing in the early postoperative period after cardiac surgery corrects LV dyssynchrony and has better hemodynamic results than DDD RV pacing.
Assuntos
Terapia de Ressincronização Cardíaca/métodos , Doenças das Valvas Cardíacas/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Cirurgia Torácica , Idoso , Ecocardiografia Tridimensional , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Isquemia Miocárdica/complicações , Isquemia Miocárdica/cirurgia , Período Pós-Operatório , Estudos ProspectivosRESUMO
Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the aim of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45-min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial ischemia- and reperfusion-induced arrhythmias and lethal myocardial injury.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Fibrilação Ventricular/tratamento farmacológico , Animais , Coração/efeitos dos fármacos , Coração/fisiopatologia , Masculino , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos , Ratos Wistar , Fibrilação Ventricular/fisiopatologiaRESUMO
Pulmonary hypertension (PH) unresponsive to pharmacological intervention is considered a contraindication for orthotopic heart transplantation (OHTX) due to risk of postoperative right-heart failure. In this prospective study, we describe our experience with a treatment strategy of improving severe PH in heart transplant candidates by means of ventricular assist device (VAD) implantation and subsequent OHTX. In 11 heart transplantation candidates with severe PH unresponsive to pharmacological intervention we implanted VAD with the aim of achieving PH to values acceptable for OHTX. In all patients we observed significant drop in pulmonary pressures, PVR and TPG (p < 0.001 for all) 3 months after VAD implantation to values sufficient to allow OHTX. Seven patients underwent transplantation (mean duration of support 216 days) while none of patients suffered right-side heart failure in postoperative period. Two patients died after transplantation and five patients are living in very good condition with a mean duration of 286 days after OHTX. In our opinion, severe PH is not a contraindication for orthotopic heart transplantation any more.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Auxiliar , Hipertensão Pulmonar/prevenção & controle , Hipertensão Pulmonar/fisiopatologia , Terapia Combinada , Contraindicações , Feminino , Insuficiência Cardíaca/complicações , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and epsilon-caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47+/-10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35+/-9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the development of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts.
Assuntos
Fármacos Cardiovasculares/farmacologia , Oclusão de Enxerto Vascular/prevenção & controle , Sirolimo/farmacologia , Túnica Íntima/efeitos dos fármacos , Animais , Fármacos Cardiovasculares/química , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos , Oclusão de Enxerto Vascular/patologia , Hiperplasia/prevenção & controle , Veias Jugulares/efeitos dos fármacos , Veias Jugulares/patologia , Poliésteres , Coelhos , Sirolimo/química , Túnica Íntima/patologiaRESUMO
AIM: Severe right heart failure remains unfrequent but fatal complication of cardiac surgical procedures. Implantation of temporary right ventricular assist device may be life-saving procedure in various situations of right heart failure as: heart transplantation, LVAD therapy and post-cardiotomy failure. The aim of the study is an introduction of the implantation technique and retrospective review of current experience with the method. MATERIAL AND METHODS: Since January 2007 isolated right ventricular assist device Levitronix CentriMag has been implanted in 16 patients. Patients were divided into 3 groups: post transplantation (post-Tx), post LVAD implantation (post-LVAD) and other cardiac procedures (OCP). Success rate of weaning from RVAD, 30-days mortality and major complications has been assessed. OUTCOMES: Distribution of implants in groups was: post-Tx 5 pts (31%), post-LVAD 6 pts (38%) and 5 in OCP group (31%). The mean support time was 12 days. Off-pump implantation was achieved in 9 pts. The device was successfully weaned in 13 (81%) patients. 30-days mortality occurred in 1 case only. CONCLUSION: Presented outcomes are encouraging for broader acceptance of the therapy. Excellent success rate has been reached in post-Tx and post-LVAD. This study emphasises decesive role of proactive approach in early indication of RVAD implantation for achieving satisfactory results.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/terapiaRESUMO
AIM OF THE STUDY: We retrospectively analyzed long-term outcome of concomitant mitral valve repair and aortic valve replacement. METHODS: From 1996 to 2009 we performed mitral valve plasty with aortic valve replacement in 50 patients. Clinical and echocardiographic data were obtained from computer database and hospital records. Missing data were obtained through mailed questionnaire. We evaluated hospital mortality, long-term survival, thromboembolic and hemorrhagic complications and TR of 3+ on follow up echocardiography. RESULTS: Four patients who had previously undergone aortic valve surgery were excluded from the study. Aortic valve pathology was stenosis in 21 patients, regurgitation in 20 and 4 patients presented with mixed aortic disease. The etiology of mitral regurgitation was rheumatic in 6, non-rheumatic in 31 and infective in 6 patients. Aortic valve was replaced with mechanical prosthesis in 22 (mean age 59) and tissue prosthesis in 24 (mean age 71) patients. Additional surgical procedure was performed in 26 patients. Follow-up was 94% complete, with a mean duration of 51 months. Hospital mortality was 13%. Two and five year survival was 79% and 64% respectively. We noted one case of retroperitoneal hemorrhage and one stroke. We recorded 9 (19.6%) patients with residual TR of more than 3+ grade on follow up echocardiography. Out of 9 patients with residual TR, 3 were operated for rheumatic and 6 for non-rheumatic mitral valve disease. One patients underwent successful mitral valve replacement with mechanical prosthesis, 3 died and 5 are treated expectantly. CONCLUSION: We conclude that concomitant mitral valve repair with aortic valve replacement has high hospital mortality, excellent long-term survival and low complication rate. The durability of mitral valve repair in patients with rheumatic mitral valve disease is limited and replacement, rather that repair should be considered in this patient group.
Assuntos
Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Valva Mitral/cirurgia , Idoso , Bioprótese , Endocardite/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgiaRESUMO
INTRODUCTION: Jehovah's Witnesses who require cardiac operation represent a specific challenge to the physicians. Members of this faith will not accept blood or blood products under any circumstances on the basis of religious grounds. Nevertheless cardiac operations belong to surgical interventions with potential severe bleeding and necessity of blood transfusions. THE AIM OF THE STUDY: The aim of this retrospective study was to analyze clinical data, operative and postoperative courses of patients operated at IKEM who refused blood transfusions. METHODS AND RESULTS: From January 1995 to August 2010, 73 Jehovah's Witnesses ranging in age from 19 to 82 years underwent cardiac surgery at our institute. Aortocoronary bypass were performed in 34 patients, valve surgery in 25 patients, 6 patients underwent concomitant aortocoronary bypass and valve surgery, 2 patients underwent aortocoronary bypass and resection of the left ventricle aneurysm and 2 patients underwent atrial septal defect repair and tricuspid valve anuloplasty. Ventricular septal sefect repair, atrial septal defect repair, Cor Cap device implantation and left ventricular epicardial electrodes implantation were performed in the other patients. Early 30-days mortality was 2.8 % (2 patients). CONCLUSION: We can conclude that cardiac surgery in Jehovah's Witnesses can be performed safety without blood transfusion and belongs to standard operating procedures at our institution.