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The idea that science must be understood in existential contradiction to religion and even theology is more of a conviction than a philosophical or experiential necessity. Indeed, we may now propose "Theological Medicine" as a new terminology for a perennial reality: that most physicians, health care providers, patients, and their caretakers experience the reality of illness within a theological framework, at least for those who have some degree of spiritual or religious belief. Developing a curriculum in Theological Medicine could develop a mechanism to offer appropriate training to healthcare providers. Such a course would have to be created and delivered by experienced physicians and nursing staff, spiritual advisors, clergy representatives such as pastors or priests from different churches or faith communities, bioethicists, psychologists, social workers, psychotherapists, patient support group members, members of institutional review boards, researchers, and even legal advisors, if available. Continuing professional education requirements also create an opportunity to introduce and evaluate competency in theological medicine, an emerging discipline that could add significant value to the lived experience of medical practice which remains based on the uniquely rich relationship between physician and patient.
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It is now more than 35 years since endothelium derived relaxing factor was identified as nitric oxide (NO). The last few decades have seen an explosion around nitric oxide biochemistry, physiology and clinical translation. The science reveals that all chronic disease is associated with decreased blood flow to the affected organ which results in increased inflammation, oxidative stress and immune dysfunction. This is true for cardiovascular disease, neurological disease, kidney, lung, liver disorders and every other major disorder. Since nitric oxide controls and regulates blood flow, oxygen and nutrient delivery to every cell, tissue and organ in the body and also mitigates inflammation, oxidative stress and immune dysfunction, a focus on restoring nitric oxide production is an obvious therapeutic strategy for a number of poorly managed chronic diseases. Since dietary nitrate is a major contributor to endogenous nitric oxide production, it should be considered as a means of therapy and restoration of nitric oxide. This review will update on the current state of the science and effects of inorganic nitrate administered through the diet on several chronic conditions and reveal how much is needed. It is clear now that antiseptic mouthwash and use of antacids disrupt nitrate metabolism to nitric oxide leading to clinical symptoms of nitric oxide deficiency. Based on the science, nitrate should be considered an indispensable nutrient that should be accounted for in dietary guidelines.
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Doenças Cardiovasculares , Nitratos , Humanos , Nitritos/metabolismo , Óxido Nítrico/metabolismo , Doenças Cardiovasculares/metabolismo , Inflamação/tratamento farmacológicoRESUMO
In the daily practice of medicine, health care providers oftentimes confront the dilemma of offering 'maximum care' based on available technologies and advances versus ethical concerns about futility. Regardless of cultural backgrounds and differences, most human beings aspire to an illness-free life, or better yet, a life lived with utmost quality and longevity. On account on ongoing advances in science and technology, the possibility of achieving "immortality" (a term used as a metaphor for an extremely long and disease-free life) is increasingly perceived as a realistic goal, which is aggressively pursued by some of the world's wealthiest individuals and corporations. However, this quest is not taking place in a philosophical or religious vacuum, which is why we attempt to evaluate the current state of knowledge on religious beliefs revolving around immortality and their alignments with today's medical advancements. The literature searches were performed using relevant databases including JSTOR and PubMed, as well as primary religious sources. Most religions present longevity as a blessing and believe in some sort of immortality, afterlife or reincarnation for the immortal soul. The quest for immortality beyond life in a "body of death" remains consistent with access to medical care and the legitimate possibility of achieving longevity-as long as certain ethical and religious parameters are preserved.
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Cultura , Religião , Humanos , Expectativa de Vida , Princípios Morais , MortalidadeRESUMO
AIMS: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? METHODS AND RESULTS: Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for individual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. CONCLUSION: Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.
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Ventrículos do Coração/citologia , Miocárdio/citologia , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Adulto , Idoso , Diferenciação Celular/fisiologia , Células Cultivadas , DNA/análise , Feminino , Transplante de Coração , Humanos , Hibridização in Situ Fluorescente , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transplante de Células-Tronco/métodos , Adulto JovemRESUMO
To ascertain the beneficial role of spiritual counseling in patients with chronic heart failure. This is a pilot study evaluating the effects of adjunct spiritual counseling on quality of life (QoL) outcomes in patients with heart failure. Patients were assigned to "religious" or "non-religious" counseling services based strictly on their personal preferences and subsequently administered standardized QoL questionnaires. A member of the chaplaincy or in-house volunteer organization visited the patient either daily or once every 2 days throughout the duration of their hospitalization. All patients completed questionnaires at baseline, at 2 weeks, and at 3 months. Each of the questionnaires was totaled, with higher scores representing positive response, except for one survey measure where lower scores represent improvement (QIDS-SR16). Twenty-three patients (n = 23, age 57 ± 11, 11 (48 %) male, 12 (52 %) female, mean duration of hospital stay 20 ± 15 days) completed the study. Total mean scores were assessed on admission, at 2 weeks and at 3 months. For all patients in the study, the mean QIDS-SR16 scores were 8.5 (n = 23, SD = 3.3) versus 6.3 (n = 18, SD = 3.5) versus 7.3 (n = 7, SD = 2.6). Mean FACIT-Sp-Ex (version 4) scores were 71.1 (n = 23, SD = 15.1) versus 74.7 (n = 18, SD = 20.9) versus 81.4 (n = 7, SD = 8.8). The mean MSAS scores were 2.0 (n = 21, SD = 0.6) versus 1.8 (n = 15, SD = 0.7) versus 2.5 (n = 4, SD = 0.7). Mean QoL Enjoyment and Satisfaction scores were 47.2 % (n = 23, SD = 15.0 %) versus 53.6 % (n = 18, SD = 16.4 %) versus 72.42 % (n = 7, SD = 22 %). The addition of spiritual counseling to standard medical management for patients with chronic heart failure patients appears to have a positive impact on QoL.
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Aconselhamento/métodos , Insuficiência Cardíaca/psicologia , Qualidade de Vida/psicologia , Espiritualidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
Heart failure (HF) is the most common reason for hospital admission for patients older than 65 years. With an aging population and improving survival in heart failure patients, the number of people living with HF continues to grow. As this population increases, the importance of treating symptoms of fatigue, dyspnea, pain, and depression that diminish the quality of life in HF patients becomes increasingly important. Palliative care has been shown to help alleviate these symptoms and improve patients' satisfaction with the care they receive. Despite this growing body of evidence, palliative care consultation remains underutilized and is not standard practice in the management of HF. With an emphasis on communication, symptom management, and coordinated care, palliative care provides an integrated approach to support patients and families with chronic illnesses. Early communication with patients and families regarding the unpredictable nature of HF and the increased risk of sudden cardiac death enables discussions around advanced care directives, health care proxies, and deactivation of permanent pacemakers or implantable cardioverter defibrillators. Cardiologists and primary care physicians who are comfortable initiating these discussions are encouraged to do so; however, many fear destroying hope and are uncertain how to discuss end-of-life issues. Thus, in order to facilitate these discussions and establish an appropriate relationship, we recommend that patients and families be introduced to a palliative care team at the earliest appropriate time after diagnosis.
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Insuficiência Cardíaca/terapia , Cuidados Paliativos , Qualidade de Vida , Planejamento Antecipado de Cuidados , Idoso , Terapia Combinada , Prestação Integrada de Cuidados de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Cuidados Paliativos/normas , Satisfação do Paciente , Qualidade da Assistência à Saúde , Assistência Terminal , Resultado do TratamentoRESUMO
BACKGROUND: Nonadherence to treatment recommendations is a leading preventable cause of rehospitalization and premature mortality in chronic heart failure (HF) patients. PURPOSE: This study examined whether self-efficacy mediates the contributions of social support and depression to treatment adherence. METHODS: A sample of 252 HF outpatients with a mean age of 54 years completed self-report questionnaires assessing depression, perceived social support, self-efficacy, and treatment adherence. RESULTS: Self-efficacy mediated the associations of social support and depression with treatment adherence after adjusting for demographic (age, gender, marital status, education, and ethnicity) and medical (New York Heart Association Classification and comorbidity) covariates. CONCLUSION: Self-efficacy explains the influence of social support and depression on treatment adherence and may be a key target for interventions to improve disease management and self-care behaviors in HF patients.
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Depressão/complicações , Transtorno Depressivo/complicações , Insuficiência Cardíaca/terapia , Cooperação do Paciente/psicologia , Autoeficácia , Apoio Social , Adaptação Psicológica , Adulto , Idoso , Depressão/psicologia , Transtorno Depressivo/psicologia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado , Inquéritos e QuestionáriosRESUMO
Heart failure is a progressive illness that carries significant morbidity and mortality. This highly prevalent illness leads to frequent, costly hospitalizations with approximately 50% of patients being readmitted within 6 months of initial hospitalization. While rehospitalization has been extensively studied in the past, little progress has been made in terms of reducing readmission rates of heart failure patients in the last decade despite increasing costs with impending resource limitations. We discuss disease-centered, physician-centered, and patient-centered factors that lead to rehospitalization as well as community/resource availability factors that contribute to rehospitalization of patients suffering from chronic heart failure. In addition, predictors of hospitalization and interventions that reduce hospitalization will be critically evaluated. With a complete understanding of heart failure rehospitalization, we hope the future holds more effective ways to prevent heart failure progression and thus rehospitalization, improved risk-stratification models to identify patients high-risk for rehospitalization, and sustained interventions that are customized according to the etiology of the clinical decline of heart failure patients that ultimately results in frequent rehospitalizations.
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Insuficiência Cardíaca , Readmissão do Paciente , Doença Crônica , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Fatores de RiscoRESUMO
Previous research has indicated that anxiety may be associated with adverse health outcomes in heart failure patients. Little research, however, has explored whether anxiety interacts with patients' coping strategies in their associations with physical functioning. The present study examined whether coping strategies moderated the association between anxiety and self-rated physical functioning in 273 heart failure patients. Hierarchical multiple regression analysis, adjusting for demographic and medical covariates, indicated that both anxiety (b=1.15, ß=0.46, P<0.001) and avoidant coping (b=0.43, ß=0.16, P<0.01) were significantly associated with poorer physical functioning in separate models. Results also demonstrated a significant interaction between avoidant coping and anxiety (b=0.56, ß=0.14, P<0.01), such that the association between anxiety and poorer physical functioning was stronger for patients who frequently used avoidant coping strategies than for those who avoided less frequently. Approach coping, however, was not directly associated with physical functioning, nor did it moderate the association between anxiety and physical functioning. The findings suggest that anxious heart failure patients who engage in avoidant coping may be at particular risk for physical dysfunction.
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Adaptação Psicológica , Ansiedade/psicologia , Insuficiência Cardíaca/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Emoções , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Autoimagem , Autorrelato , Inquéritos e QuestionáriosRESUMO
Heart failure (HF) is a chronic progressive disease with marked morbidity and mortality. Patients enduring this condition suffer from fluctuations in symptom burden such as fatigue, shortness of breath, chest pain, sexual dysfunction, dramatic changes in body image and depression. As physicians, we often ask patients to trust in our ability to ameliorate their symptoms, but oftentimes we do not hold all of the answers, and our best efforts are only modestly effective. The suffering endured by these individuals and their families may even call into question one's faith in a higher power and portends to significant spiritual struggle. In the face of incurable and chronic physical conditions, it seems logical that patients would seek alternative or ancillary methods, notably spiritual ones, to improve their ability to deal with their condition. Although difficult to study, spirituality has been evaluated and deemed to have a beneficial effect on multiple measures including global quality of life, depression and medical compliance in the treatment of patients with HF. The model of HF treatment incorporates a multidisciplinary approach. This should involve coordination between primary care, cardiology, palliative care, nursing, patients and, importantly, individuals providing psychosocial as well as spiritual support. This review intends to outline the current understanding and necessity of spirituality's influence on those suffering from HF.
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Insuficiência Cardíaca/reabilitação , Religião e Medicina , Espiritualidade , Doença Crônica , Insuficiência Cardíaca/psicologia , Transplante de Coração , Humanos , Cuidados Paliativos , Cooperação do Paciente , Qualidade de Vida , Religião , AutocuidadoRESUMO
BACKGROUND: A new generation of therapeutic devices has expanded the options for managing advanced heart failure. We examined the outcomes of cardiac contractility therapy in a series of 10 patients with chronic heart failure. METHODS: Ten patients with chronic heart failure were nonrandomly selected to receive cardiac contractility modulation therapy. Hemodynamics, left ventricular ejection fraction, functional capacity, and clinical outcomes were evaluated at baseline and after 6 months of therapy. RESULTS: Eight male and 2 female patients (mean [SD] age, 63.4 [9.4] years) received cardiac contractility modulation therapy. Between baseline and 6-month follow-up, mean (SD) left ventricular ejection fraction improved from 27.1% (4.18%) to 35.1% (9.89%), New York Heart Association class declined from 3.9 (0.32) to 2.44 (0.52), and 6-minute walk test distance increased from 159.2 (93.79) m to 212.4 (87.24) m. Furthermore, the mean (SD) number of hospital admissions within the 6 months before cardiac contractility modulation therapy was 2.4 (2.27) compared with 1 (1.52) during the 6 months after therapy. CONCLUSION: Cardiac contractility modulation therapy improved physical functioning and reduced hospital admissions in these patients.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Volume Sistólico , Resultado do Tratamento , Contração Miocárdica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Doença CrônicaRESUMO
BACKGROUND: Few studies have examined the prospective influences of depression and anxiety on physical health functioning in heart failure (HF) patients. Prior studies were also limited by employing psychological measures containing somatic items confounded with HF symptoms. PURPOSE: This study examined whether depression, anxiety, social support, and their changes predicted the decline of physical functioning in HF patients over 6 months. METHODS: Participants were 238 HF patients among whom 164 provided follow-up data. The depression and anxiety measures did not contain somatic items. RESULTS: After controlling for baseline physical functioning and demographic and medical covariates, baseline depression and its increase, as well as baseline anxiety and its increase, independently predicted greater decline in physical functioning at 6 months. Social support and its change were not associated with either concurrent or follow-up physical functioning. CONCLUSIONS: Depression, anxiety, and their changes independently predicted the decline of physical health functioning over 6 months.
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Atividades Cotidianas/psicologia , Ansiedade/psicologia , Depressão/psicologia , Nível de Saúde , Insuficiência Cardíaca/psicologia , Ansiedade/complicações , Ansiedade/epidemiologia , Depressão/complicações , Depressão/epidemiologia , Feminino , Florida/epidemiologia , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida/psicologia , Fatores de Risco , Apoio SocialRESUMO
Swine-origin influenza A (H1N1) virus was identified in March of 2009 in Mexico and the United States. The virus spread rapidly, becoming pandemic by June. Previous studies examined the role of influenza infection in cardiovascular disease, however, we present the first case of an acute myocardial infarction in a healthy patient specifically associated with the novel viral infection. This case underscores the importance of prompt diagnosis and treatment as well as vigilance on behalf of health care workers in treating patients affected with influenza A (H1N1). Consideration of this previously undescribed pathology may play a significant role in the coming debates over vaccines and access.
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Infarto Miocárdico de Parede Anterior/virologia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Cateterismo Cardíaco , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico , Eletrocardiografia , Humanos , Masculino , Adulto JovemRESUMO
Heart transplantation is performed on approximately 4,000 patients per year worldwide and is considered the last resort for treatment of end-stage heart diseases. Due to persistent organ shortage, resources are limited, waiting periods are extensive, and patients still die while being on a waiting list for transplantation. The role of all churches and the support of the representatives of the churches are critical for the spiritual wellbeing of patients awaiting heart transplantation as well as for prospective individual organ donors and their families. The supportive role of the Roman Catholic Church and the recent statement of Pope Benedict XVI on organ donation are discussed.
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Catolicismo , Transplante de Coração , Religião e Medicina , HumanosRESUMO
Chronic heart failure is a lifelong disease that involves a large variety of symptoms and, ultimately, the entire organism relatively early in the disease process. At least in part, this is in contrast to other chronic conditions such as diabetes, renal failure or cancer. Modern treatment of patients with chronic heart failure goes beyond the mere prescription of vasodilators or inotropes. The multitude of multi-organ involvements and associated symptoms unrelated to pure cardiac contractile failure, as well as the psychosocial burden for patients and their direct environment, calls for a re-engagement with the philosophical aspects of medical care. Such a process may well challenge the approach commonly taken by health care providers. We further suggest a broader and more holistic view of medical care--in this case in regard to heart failure--and one that is based on patients' and physicians' understanding of health and disease, autonomy, suffering, existential values and expectations that might positively affect treatment strategies and outcomes.
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Insuficiência Cardíaca , Assistência Centrada no Paciente/organização & administração , Filosofia Médica , Doença Crônica , Insuficiência Cardíaca/fisiopatologia , Humanos , Modelos Teóricos , AutocuidadoRESUMO
Deciding who should receive maximal technological treatment options and who should not represents an ethical, moral, psychological and medico-legal challenge for health care providers. Especially in patients with chronic heart failure, the ethical and medico-legal issues associated with providing maximal possible care or withholding the same are coming to the forefront. Procedures, such as cardiac transplantation, have strict criteria for adequate candidacy. These criteria for subsequent listing are based on clinical outcome data but also reflect the reality of organ shortage. Lack of compliance and non-adherence to lifestyle changes represent relative contraindications to heart transplant candidacy. Mechanical circulatory support therapy using ventricular assist devices is becoming a more prominent therapeutic option for patients with end-stage heart failure who are not candidates for transplantation, which also requires strict criteria to enable beneficial outcome for the patient. Physicians need to critically reflect that in many cases, the patient's best interest might not always mean pursuing maximal technological options available. This article reflects on the multitude of critical issues that health care providers have to face while caring for patients with end-stage heart failure.
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Reanimação Cardiopulmonar/ética , Insuficiência Cardíaca/terapia , Transplante de Coração/ética , Coração Auxiliar/ética , Papel do Doente/ética , Reanimação Cardiopulmonar/psicologia , Gerenciamento Clínico , Humanos , Seleção de Pacientes , Qualidade de VidaRESUMO
The prevalence of erectile dysfunction (ED) has increased in recent decades. Although many treatments offer some benefits for patients with ED, unmet therapeutic needs remain, and promising new approaches are under investigation. One of these approaches is the use of stem-cell (SC) therapy for ED. We comprehensively reviewed the published literature and ongoing phase 1 and phase 2 trials and identified 27 trials by using SC therapy to treat ED. Of the 27 trials, three have been withdrawn, nine have published results, six are complete but without published results, and nine trials are ongoing or have an "unknown" status. Our analysis revealed that SC therapy represents a promising option to treat ED, although published data exist for less than 100 patients. Large placebo-controlled trials with longer follow-up are needed to confirm the long-term safety and efficacy of SC therapy for ED.
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Disfunção Erétil , Disfunção Erétil/terapia , Humanos , Masculino , Transplante de Células-TroncoRESUMO
Autophagy plays a critical and seemingly dual-purposed role in cardiomyocytes, being implicated as a mechanism of both cellular survival, for example, during ischemia/reperfusion injury and a mechanism of cell death at stages in which progressive myocyte alterations are beyond repair. This review aims to highlight the current literature as it relates to autophagy in cardiomyocytes. It provides background into the mechanisms of cell death, discusses the details that are known about the ubiquitin proteasome system and autophagy, delves into the pathways that are known to initiate and inhibit autophagy, and comments on the role of autophagy in cardiomyocyte homeostasis and cell death.
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Apoptose , Autofagia , Homeostase , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Morte Celular , Insuficiência Cardíaca/enzimologia , Humanos , Traumatismo por Reperfusão Miocárdica/enzimologia , Miocárdio/enzimologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Estresse Fisiológico , Ubiquitina/metabolismoRESUMO
INTRODUCTION: The impact of sexual dysfunction (SD) on mental and physical health after heart transplantation (HTx) has not been established. AIM: We investigated the relationship of SD on quality of life (QoL), physical and mental health, and depressive symptoms after HTx. MAIN OUTCOME MEASURES: We evaluated SD according to the International Index of Erectile Dysfunction and the Female Sexual Function Index. QoL, physical and mental health were assessed using: 1) Short Form 12 Health Survey Questionnaire, 2) Quality of Life Enjoyment and Satisfaction Questionnaire--Short Form, and two depressive symptoms questionnaires: 1) Beck Depression Inventory-II and 2) Quick Inventory Depressive Symptomatology-Self Report. METHODS: We enrolled patients who were greater than 6 months post HTx. Patients unable to read English, had pelvic surgery or trauma, urogenital abnormalities, or sexually inactive were excluded. RESULTS: Out of 79 subjects that were screened, 33 men and 6 women participated (mean age 61.4 + 1.4). Response rates were at least 82% for all questionnaires. Overall prevalence of SD was 61%, with 78% of men being affected and 50% of women. There was no significant difference in measures between genders. HTx recipients with SD reported significantly worse QoL on measures of physical health when compared to those without SD. After HTx, patients suffering from SD had significantly worse general health (P = 0.02) and physical health (P = 0.02), including physical functioning (P = 0.01) and physical role limitation (P = 0.01). In contrast, mental health and depressive symptoms after HTx were not significantly different between those with and without SD. CONCLUSIONS: After HTx a high prevalence of SD remains among both men and women. Patients with SD had worse general and physical health but not depressive symptoms when compared to those without SD. The contributing factors may be more related to physical rather than psychological causes.
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Disfunção Erétil/psicologia , Transplante de Coração/psicologia , Complicações Pós-Operatórias/psicologia , Qualidade de Vida/psicologia , Disfunções Sexuais Fisiológicas/psicologia , Atividades Cotidianas/classificação , Atividades Cotidianas/psicologia , Idoso , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/epidemiologia , Feminino , Seguimentos , Nível de Saúde , Transplante de Coração/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIM OF THE STUDY: Cholesterol is a known risk factor in aortic stenosis and valve degeneration, and the liver X receptor (LXR) is a regulator of cholesterol and phospholipid metabolism. It was hypothesized that an LXR agonist would reduce calcium and lipid deposition in aortic valves. METHODS: Apolipoprotein E-/- (ApoE-/-) mice fed a high-fat diet were implanted with glutaraldehyde-fixed porcine valve fragments. The animals were treated with either the LXR agonist T1317 or vehicle for eight weeks. RESULTS: The LXR agonist reduced lipid deposition in native aortic roots and sinuses about two-fold (p < 0.05), and echocardiography revealed lower transvalvular velocities in vivo (p < 0.05). Similarly, treatment with the LXR agonist significantly reduced the calcium content (by ca. 50%, p < 0.05) and lipid content (by ca. 20%, p < 0.01) of explanted porcine valve tissue. Serum low-density lipoprotein (LDL) and total cholesterol levels were also lower in treated mice (p < 0.01). Serum levels of the inflammatory chemokine platelet factor 4 were reduced by 30% compared to controls. Cultured valvular cells treated with oxidized LDL (ox-LDL) developed greater numbers of calcific nodules. The ox-LDL treatment of valvular endothelial cells increased adhesion to mononuclear cells, while the LXR agonist reversed both the increase in adhesion and vascular cell adhesion protein-1 expression mediated by ox-LDL. CONCLUSION: The data acquired suggested that calcium and lipid deposition in heart valves can be altered by inhibiting lipid metabolism via LXR, and that the mechanism may involve inflammatory cell signaling. These results indicate that enhancement of cholesterol efflux activity may have the potential to reduce bioprosthetic and native valve degeneration.