[Fulminant myocarditis]. / Miocardite fulminante - a propósito de um caso clínico.

A 46-year-old woman was admitted due to diplopia because of ophthalmoplegia, which improved with corticosteroid therapy. Eight days later, she was admitted with fulminant myocarditis in cardiogenic shock, with severe left ventricular dysfunction and frequent episodes of nonsustained ventricular tachycardia. As there was no clinical improvement, an endomyocardial biopsy was performed that revealed inflammatory infiltrate, vasculitis, and PCR positive for cytomegalovirus, Epstein-Barr virus, parvovirus B19 and enterovirus. Left ventricular function recovered with heart failure treatment and corticosteroids. Three months later, after progressive withdrawal of prednisolone, there was recurrence of myocarditis and left ventricular dysfunction, which was successfully treated by restarting corticosteroid therapy. One month later she was readmitted with fulminant myocarditis which again responded to steroids. She intermittently presented cutaneous purpura lesions. At this time the provisional diagnosis was vasculitis and she started monthly cycles of cyclophosphamide. Before the second cycle she was admitted with pneumonia and ventricular dysfunction and died.

Mean pulmonary arterial pressure after percutaneous mitral valvuloplasty predicts long-term adverse outcomes.

INTRODUCTION AND AIM: Percutaneous mitral valvuloplasty (PMV) is an effective treatment option for mitral stenosis (MS), but its success is assessed on the basis of clinical and echocardiographic outcomes in studies with relatively short follow-up. We aimed to characterize a cohort of patients undergoing PMV with long-term follow-up and to determine independent predictors of post-PMV mitral re-intervention and event-free survival. METHODS: We studied 91 consecutive patients with MS who underwent PMV with a median clinical follow-up duration of 99 months. Two endpoints were considered: post-PMV mitral re-intervention (PMV or mitral surgery) and a composite clinical events endpoint including cardiovascular death, mitral valve re-intervention and hospital admission due to decompensated heart failure. We compared patients who required post-PMV mitral re-intervention with those who did not during follow-up. RESULTS: The study population included 83.5% females and mean age was 48.9±13.9 years. The 1-, 3-, 5-, 7- and 9-year rates of clinical event-free survival were 93.0±2.8%, 86.0±3.9%, 81.0±4.4%, 70.6±5.6%, and 68.4±5.8%, respectively. The 1-, 3-, 5-, 7- and 9-year rates of mitral re-intervention-free survival were 98.8±1.2%, 97.5±1.7%, 92.1±3.1%, 85.5±4.5%, and 85.5±4.5%, respectively. The median time to mitral re-intervention was 6.2 years. Patients who required mitral re-intervention during follow-up were younger (43.3 vs. 51.2 years, p=0.04) and had higher pre- and post-PMV mitral gradient (14.9 vs. 11.5 mmHg, p=0.02 and 6.4 vs. 2.1 mmHg, p<0.001) and higher post-PMV mean pulmonary artery pressure (mPAP) (30.0 vs. 23.2 mmHg, p=0.01). In a Cox proportional hazards model, mPAP ≥25 mmHg was the sole predictor of both mitral re-intervention (HR 5.639 [1.246-25.528], p=0.025) and clinical events (HR 3.622 [1.070-12.260], p=0.039). CONCLUSION: In our population, immediate post-PMV mPAP was the sole predictor of post-PMV mitral intervention. These findings may help identify patients in need of closer post-PMV follow-up.

[Anticoagulation in elderly patients with atrial fibrillation: from the guidelines to the daily medical practice]. / Terapêutica anti trombótica no idoso com fibrilhação auricular: das guidelines à prática clínica.

BACKGROUND: Atrial fibrillation (AF) is a common medical problem with increasing prevalence among the elderly. Warfarin is effective in the prevention of AF-related-stroke but is often underutilized, especially in high-risk populations, like the elderly. OBJECTIVES: To determine, in a group of elderly patients with AF, if those treated in-line with the clinical recommendations differ from patients who were not, regarding morbidity and mortality and also to determine independent predictors of mortality. A second objective was to verify if the CHADS2 score is a good predictor of thromboembolic risk in the elderly. POPULATION AND METHODS: A total of 161 consecutive elderly patients with AF admitted in a single centre were evaluated. Clinical follow-up was available for 88.4%, with a mean duration of 9 months. RESULTS: Mean age was 80.9 ± 6.6 years; 96.3% of the patients had permanent AF, with controlled ventricular rate in 56.4%. Previous stroke was verified in 30.4%. Only 37.3% had oral anticoagulation at hospital discharge, despite 87.6% had guideline recommendation. Cumulative mortality rate in follow-up was 48.4% and the thromboembolism rate was 8.1%. We verified that CHADS2 score was a good predictor of thromboembolic risk in this population (c-statistic=0.742). Clinical follow-up showed that patients treated according with the clinical recommendations were more likely to survive (33.33% vs 53.93%; p=0.048). Multivariate analysis showed that age >80 years, renal disease, neoplasm and neuropsychic disease as independent predictors of mortality (c-statistic=0.83). CONCLUSION: A gap of 50% existed between the guideline recommendations and actual practice. The use of risk stratification scores can help guide the decision to use anticoagulation in older patients with AF. Elderly patients treated according with the clinical recommendations had a better prognosis.

Impact of previous insulin therapy on the prognosis of diabetic patients with acute coronary syndromes / Impacto da insulinoterapia prévia no prognóstico dos pacientes diabéticos com síndromes coronárias agudas

OBJECTIVE: To determine whether previous insulin treatment independently influences subsequent outcomes in diabetic patients with ACS (acute coronary syndromes). SUBJECTS AND METHODS: 375 diabetic patients with ACS, divided in 2 groups: Group A (n = 69) - previous insulin and Group B (n = 306) - without previous insulin. Predictors of 1-year mortality and major adverse cardiac events (MACE) were analyzed by Cox regression analysis. RESULTS: Group A had more previous stroke (17.4 percent vs. 9.2 percent, p = 0.047) and peripheral artery disease (13.0 percent vs. 3.6 percent, p = 0.005). They had significantly higher admission glycemia and lower LDL cholesterol. There were no significant differences in the type of ACS, in 1-year mortality (18.2 percent vs. 10.4 percent, p = 0.103) or MACE (32.1 percent vs. 23.0 percent, p = 0.146) between groups. In multivariate analysis, insulin treatment was neither an independent predictor of 1-year mortality nor of MACE. CONCLUSION: Despite the more advanced atherosclerotic disease, diabetics under insulin had similar outcomes to those without insulin. Insulin may protect diabetics from the expected poor adverse outcome of an advanced atherosclerotic disease.

OBJECTIVO: Avaliar se a insulinoterapia prévia influencia de forma independente o prognóstico de diabéticos após uma síndrome coronária aguda (SCA). SUJEITOS E MÉTODOS: 375 doentes diabéticos com SCA, divididos em 2 grupos: Grupo A (n = 69) - sob insulinoterapia prévia e Grupo B (n = 306) - sem insulinoterapia prévia. Os preditores de mortalidade a um ano e de eventos cardíacos adversos maiores (MACE) foram determinados pela regressão de Cox. RESULTADOS: Verificou-se maior proporção de acidente vascular cerebral prévio (17,4 por cento vs. 9,2 por cento, p = 0,047) e doença arterial periférica (13,0 por cento vs. 3,6 por cento, p = 0,005) no Grupo A. Esses doentes apresentaram glicemia na admissão significativamente mais elevada e LDL inferior. Não houve diferenças estatisticamente significativas no tipo de SCA, na mortalidade (18,2 por cento vs. 10,4 por cento, p = 0,103) e MACE (32,1 por cento vs. 23,0 por cento, p = 0,146) em um ano entre os 2 grupos. Na análise multivariada, a insulinoterapia prévia não foi preditor independente nem de mortalidade, nem de MACE em 1 ano. CONCLUSÃO: Apesar da doença aterosclerótica mais avançada, os diabéticos previamente insulino-tratados têm um prognóstico semelhante aos não insulino-tratados. A insulinoterapia crônica poderá proteger os diabéticos da evolução desfavorável própria da doença aterosclerótica avançada.

Cardiac transplantation: five years' activity.

OBJECTIVE: To analyze the initial five years experience of the new heart transplant program of Coimbra University Hospitals. METHODS: Between November 2003 aid December 2008, 132 patients were transplanted, with a mean age of 52.0 years (range 3-71 years), of whom 98 were male (74%). Half of the patients had dilated cardiomyopathy and 33% ischemic cardiomyopathy. The mean age of donors was 31.7 years and 102 were male (77%). Donor hearts were harvested at a distance in 62% of cases. There was a gender mismatch between donor and recipient (F:M) in 19% of cases and ABO blood type disparity (not identical but compatible) in 11%. In all cases we used the technique of total transplantation with bicaval anastomosis, modified in this center. Mean ischemia time was 88.9 +/- 32.2 minutes. All patients received induction therapy with basiliximab and methylprednisolone. RESULTS: Six patients (4.5%) died within 30 days or during hospitalization, due to graft failure in four and hyperacute rejection in two. Two patients required prolonged ventilation, ten (8%) required inotropic support for more than 48 hours, and four required pacemaker implantation. Mean hospital stay was 15.6 +/- 15.2 days (median 13 days). Ninety percent of patients (116/129) were maintained on triple immunosuppressive therapy, including cyclosporine, the remainder receiving tacrolimus. In 23 patients it was necessary to change the immunosuppressive regimen due to renal and/or tumoral complications, or humoral rejection. All patients are followed regularly in the Surgical Center. Thirteen patients (10%) died late of cancer (6 patients), infection (4 patients), and pancreatitis, pulmonary hypertension and suicide (one patient each). Twenty-two patients (17%) had 25 episodes of cellular rejection (> or = 2R), with clinical consequences in only one case, and five had humoral rejection (3.9%). No patients died of late rejection, but there is evidence of mild graft vascular disease in one. Actuarial survival (Kaplan-Meier) at one and five years was 90% and 82%, respectively. CONCLUSION: In this initial series of five years we obtained results equivalent to or bette than those in centers with wider and longer experience, aided by self-correction arising from our own experience. This program has increased the rate of cardiac transplantation in Portugal to above the European average.

Challenges in vascular repair by endothelial progenitor cells in diabetic patients.

Endothelial progenitor cells (EPCs) are a special type of stem cells, derived from bone marrow that can be mobilized to the peripheral circulation in response to many stimuli. EPCs play a crucial role in the vascular repair, as well as in neovascularization processes. Recent studies have shown that EPCs are impaired, both in number and function, in diabetic patients independently of other cardiovascular risk factors. Accelerated atherosclerosis is probably the most devastating among diabetes complications and endothelial dysfunction might be the beginning of the atherosclerosis. The impairment of EPCs seems to significantly contribute to atherogenesis and atherosclerotic disease progression in diabetes. Autologous EPCs therapy represents a novel treatment option for vascular complications requiring therapeutic revascularization and vascular repair. Diabetic patients represent a population that may benefit from cell-based therapy; however the dysfunction of their endogenous cells may limit the feasibility of this approach. In fact, EPCs isolated from these patients for autologous cell transplantation may retain their dysfunctional characteristics in vivo and as a consequence display a reduced capacity to improve therapeutic neovascularization. In the present review, we summarize the most relevant mechanisms of EPC dysfunction in diabetes.

Can we improve outcomes in patients with previous coronary artery bypass surgery admitted for acute coronary syndrome?

INTRODUCTION AND OBJECTIVES: Prognosis and in-hospital management of patients with acute coronary syndrome (ACS) and a history of coronary artery bypass graft (CABG) surgery are still debated. The objective of this study was to characterize ACS patients with a CABG and to compare their in-hospital and postdischarge outcomes with those of patients without a CABG. METHODS: This ongoing prospective observational study included 1,495 consecutive patients admitted for ACS to a coronary care unit and followed up for a mean of 19 months. There were two groups: group A (n=73), with CABGs; and group B (n=1,223), without CABGs. RESULTS: Group A patients were more often male (86.3% versus 69.1%; P=.002), and more frequently had a history of diabetes, myocardial infarction and heart failure. Group B patients more frequently had ST-elevation myocardial infarction, and had a higher median ejection fraction (53% [interquartile range, 47%-60%] vs. 50% [42%-55%]; P< .01) and peak troponin-I concentration. There was no difference in the use of invasive techniques. Regarding medication, Group B patients were more likely to receive dual antiplatelet therapy at discharge. No significant difference was observed in in-hospital mortality (9.5% versus 5.9%; P=.2) or mortality at 1 month, 6 months or 1 year (9.8% versus 9.1%; log-rank test, P=.87) and the cumulative major adverse cardiac event rate was equally low in both groups. The presence of a CABG was associated with more readmissions for unstable angina (11.3% vs. 3.1%; P< .01). CONCLUSIONS: In our ACS patients, the presence of a CABG had no significant influence on short- or medium-term outcomes, such as all-cause mortality and adverse cardiac events.

Pulmonary veno-occlusive disease: a case report.

The authors present the case of a 22-year-old female patient, white, referred to the cardiovascular outpatient clinic in November 2006 for pulmonary arterial hypertension. Complementary diagnostic exams revealed elevated pulmonary arterial pressure, normal capillary wedge pressure and a reduced cardiac index on invasive hemodynamic study. A high-resolution pulmonary CT scan identified a diffuse ground-glass opacity with a centrilobular pattern, and a marked decrease in CO diffusion on respiratory function assessment. An open lung biopsy was accordingly performed in January 2007, which was compatible with pulmonary arterial hypertension with associated venous lesions: pulmonary veno-occlusive disease. Therapy was begun with oxygen support, warfarin and bosentan (62.5 mg twice a day) Monthly follow-up was maintained, but her clinical and functional status progressively worsened and one year after the diagnosis the patient was admitted to our heart failure clinic for acute right heart failure. She was stabilized with inotropic therapy and diuretics and was subsequently referred to an international pulmonary transplantation center. The authors highlight the diagnostic challenge of this entity and its poor response to medical therapy and dismal prognosis.

A importância de um EGC normal em síndromes coronarianas agudas sem supradesnivelamento do segmento ST / The importance of a normal ECG in non-ST elevation acute coronary syndromes / La importancia de un ECG normal en síndromes coronarios agudos sin supradesnivel del segmento ST

Fundamento: O eletrocardiograma (ECG) de admissão tem um grande impacto no diagnóstico e tratamento de síndromes coronarianas agudas (SCA) sem supradesnivelamento do segmento ST. Objetivo: Avaliar o impacto do ECG de admissão no prognóstico da SCA sem supradesnivelamento de ST. População: estudo prospectivo, contínuo, observacional, de 802 pacientes com SCA sem supradesnivelamento de ST de um único centro. Métodos: Os pacientes foram divididos em 2 grupos: A (n=538) - ECG Anormal e B (n=264) - ECG Normal. ECG Normal era sinônimo de ritmo sinusal sem alterações isquêmicas agudas. Um seguimento clínico de um ano foi realizado tendo como alvo todas as causas de mortalidade e a taxa de eventos cardíacos adversos maiores (MACE). Resultados: Os pacientes do Grupo A eram mais velhos (68,7±11,7 vs. 63,4±12,7 anos, p<0,001), apresentavam classes Killip mais altas e pico mais altos de biomarcadores de necrose miocárdica. Além disso, apresentavam menor fração de ejeção do ventrículo esquerdo (FEVE) (52,01±10,55 vs. 55,34± 9,51 por cento, p<0,001), taxa de filtração glomerular, hemoglobina inicial, e níveis de colesterol total. Os pacientes do Grupo B foram mais frequentemente submetidos à estratégias invasivas (63,6 vs. 46,5 por cento, p<0,001) e tratados com aspirina, clopidogrel, beta-bloqueadores e estatinas. Eles também apresentavam mais frequentemente uma anatomia coronária normal (26,2 vs. 18,0 por cento, p=0,45). Foi observada uma tendência à maior mortalidade hospitalar no grupo A (4,6 vs. 1,9 por cento, p=0,054). A análise de Kaplan-Meyer mostrou que a sobrevivência de 1 mês e um ano (95,1 vs. 89.5 por cento, p=0.012) era mais alta no grupo B e o resultado manteve-se significante em um modelo de regressão de Cox (ECG normal HR 0,45 (0,21 - 0,97). Não houve diferenças em relação à taxa de MACE. Conclusão: Em nossa população de pacientes com SCA sem supradesnivelamento de ST, um ECG normal foi um marcador inicial para um bom prognóstico.

Background: Admission ECG has a major impact on the diagnosis and management of non-ST elevation acute coronary syndromes (ACS). Objective: To assess the impact of the admission ECG on prognosis over non-ST ACS. Population: prospective, continuous, observational study of 802 non-ST ACS patients from a single center. Methods: Patients were divided in 2 groups: A (n=538) - Abnormal ECG and B (n=264) - Normal ECG. Normal ECG was synonymous of sinus rhythm and no acute ischemic changes. A one-year clinical follow up was performed targeting all causes of mortality and the MACE rate. Results: Group A patients were older (68.7±11.7 vs. 63.4±12.7Y, p<0.001), had higher Killip classes and peak myocardial necrosis biomarkers. Furthermore, they had lower left ventricular ejection fraction (LVEF) (52.01±10.55 vs. 55.34± 9.51 percent, p<0.001), glomerular filtration rate, initial hemoglobin, and total cholesterol levels. Group B patients were more frequently submitted to invasive strategy (63.6 vs. 46.5 percent, p<0.001) and treated with aspirin, clopidogrel, beta blockers and statins. They also more often presented normal coronary anatomy (26.2 vs. 18.0 percent, p=0.45). There was a trend to higher in-hospital mortality in group A (4.6 vs. 1.9 percent, p=0.054). Kaplan-Meyer analysis showed that at one month and one year (95.1 vs. 89.5 percent, p=0.012) survival was higher in group B and the result remained significant on a Cox regression model (normal ECG HR 0.45 (0.21 - 0.97). There were no differences regarding the MACE rate. Conclusion: In our non-ST elevation ACS population, a normal ECG was an early marker for good prognosis.

Fundamento: El electrocardiograma (ECG) de ingreso tiene un gran impacto en el diagnóstico y tratamiento de síndromes coronarios agudos (SCA) sin supradesnivel del segmento ST. Objetivo: Evaluar el impacto del ECG de ingreso en el pronóstico del SCA sin supradesnivel de ST. Métodos: Población: estudio prospectivo, continuo, observacional, de 802 pacientes con SCA sin supradesnivel de ST de un único centro. Los pacientes se dividieron en 2 grupos: A (n=538) - ECG Anormal y B (n=264) - ECG Normal. ECG Normal era sinónimo de ritmo sinusal sin alteraciones isquémicas agudas. Se realizó un seguimiento clínico de un año teniendo como objetivo todas las causas de mortalidad y la tasa de eventos cardíacos adversos mayores (MACE). Resultados: Los pacientes del Grupo A eran más viejos (68,7±11,7 vs 63,4±12,7 años, p<0,001), presentaban clases Killip más altas y picos más altos de biomarcadores de necrosis miocárdica. Además de ello, presentaban menor fracción de eyección del ventrículo izquierdo (FEVI) (52,01±10,55 vs 55,34± 9,51 por ciento, p<0,001), tasa de filtrado glomerular, hemoglobina inicial, y niveles de colesterol total. Los pacientes del Grupo B fueron sometidos más frecuentemente a estrategias invasivas (63,6 vs 46,5 por ciento, p<0,001) y tratados con aspirina, clopidogrel, betabloqueantes y estatinas. Éstos también presentaban más frecuentemente una anatomía coronaria normal (26,2 vs 18,0 por ciento, p=0,45). Se observó una tendencia a la mayor mortalidad hospitalaria en el grupo A (4,6 vs 1,9 por ciento, p=0,054). El análisis de Kaplan-Meyer mostró que la sobrevida de 1 mes y un año (95,1 vs 89. 5 por ciento, p=0.012) era más alta en el grupo B y el resultado se mantuvo significativo en un modelo de regresión de Cox (ECG normal HR 0,45 (0,21 - 0,97). No hubo diferencias con relación a la tasa de MACE. Conclusión: En nuestra población de pacientes son SCA sin supradesnivel de ST, un ECG normal fue un marcador inicial para un buen pronóstico.

Stimulation of endothelial progenitor cells: a new putative effect of several cardiovascular drugs.

The role of vascular endothelium in cardiovascular disorders is well recognized. Mature endothelial cells contribute to the repair of endothelial injury, but they only have a limited capacity to do so. This has led to growing interest and further investigation into circulating endothelial progenitor cells (EPCs) and their role in vascular healing, repair, and postnatal neovascularization. The current perception of vascular health is that of a balance between ongoing injury and resultant vascular repair, mediated at least in part by circulating EPCs. Circulating EPCs play an important role in accelerating endothelialization at areas of vascular damage, and EPC enumeration is a viable strategy for assessing reparative capacity. Recent studies have shown that EPCs are affected both in number and function by several cardiovascular risk factors as well as various cardiovascular disease states, such as hypertension, hypercholesterolemia, and coronary artery disease. The present review summarizes the most relevant studies on the effects of cardiovascular drugs on vascular function and EPCs, focusing on their mechanisms of action.

Carney complex: a case report.

Cardiac myxoma is the most common benign cardiac tumor, and 10% of cases are familial forms. The authors present a review of the literature on the Carney complex, and a case report of a 68-year-old man with a cardiac mass, associated with a significant family history and a diagnosis of coronary embolism.

The debate concerning oral anticoagulation: whether to suspend oral anticoagulants during dental treatment.

The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.

Cardiac allograft systolic function. Is the aetiology (ischaemic or idiopathic) a determinant of ventricular function in the heart transplant patient?

The natural history of the LV systolic function (LV-SF) and functional capacity of survivors of heart transplantation (Htx) has not been defined. Some investigators suggest that SF may be different in recipients with different pre-transplant aetiologies: ischaemic or dilated, idiopathic disease. Routine transthoracic echocardiograms (TTE) were performed during a 1-year follow-up in 48 Htx recipients (total 864 examinations; mean 18/patient). Patients were divided into two groups based on pre-transplant diagnosis: ischaemic (CAD-CMP: n=13, age 54+/-1.7 years, 23% females) and idiopathic dilated cardiomyopathy (ID-CMP: n=35, age 51+/-2.3 years, 26% females). Patients with valvular and toxic aetiology were excluded. All patients underwent left ventriculography (VENT) 12-15 months after Htx. The majority of 1-year survivors of Htx maintained normal LV-SF: mean LVEF 65+/-4% by echocardiography and 68+/-3% by ventriculography, but in the ID-CMP group LVEF was significantly higher: 67+/-4% vs. 62+/-4% (TTE) and 77+/-4% vs. 60+/-4% (VENT), without significant differences in functional capacity (NYHA). 82.9% of ID-CMP patients had LVEF >65% vs. 39% in CAD-CMP. The incidence of acute cellular rejection, freedom from cardiac vasculopathy, renal failure, diabetes, hypertension and pre-transplant alloantibody level was similar. Our study shows a strong correlation between pre-transplant heart disease and the systolic function of the cardiac allograft at 1-year follow-up.

Carvedilol as a protector against the cardiotoxicity induced by anthracyclines (doxorubicin).

The myocardium is a tissue rich in mitochondria, which are of great importance in the maintenance of cardiac function. Carvedilol is a non-selective beta-blocker which, besides its neuroprotective and vasculoprotective properties, has cardioprotective and antioxidant effects. The number of patients undergoing chemotherapy is increasing, and doxorubicin is one of the most potent antineoplastics. However, its use is frequently associated with cardiotoxicity, which results from the interaction between doxorubicin and the reduced form of exogenous nicotinamide adenine dinucleotide dehydrogenase (NADH-D), found in cardiac mitochondria, resulting in the production of reactive oxygen species (ROS). The aim of this review article is to revisit the available evidence on the cardioprotection of carvedilol when associated with doxorubicin and to explain the mechanisms underlying the benefits of their co-administration.

Ischemic preconditioning enhances fatty acid-dependent mitochondrial uncoupling.

This study tests the hypothesis that ischemic preconditioning (IP) changes fatty acid (FA)-dependent uncoupling between mitochondrial respiration and oxidative phosphorylation. We found that IP does not alter mitochondrial membrane integrity or FA levels, but enhances membrane potential decreases when FA are present, in an ATP-sensitive manner. FA hydroperoxides had equal effects in control and preconditioned mitochondria, and GTP did not abrogate the IP effect, suggesting uncoupling proteins were not involved. Conversely, thiol reductants and atractyloside, which inhibits the adenine nucleotide translocator, eliminated the differences in responses to FA. Together, our results suggest that IP leads to thiol oxidation and activation of the adenine nucleotide translocator, resulting in enhanced FA transport and mild mitochondrial uncoupling.

Massive calcification of the mitral valve annulus in an adolescent with Marfan syndrome. A case report.

Marfan syndrome (MFS) is an inherited connective tissue disorder, transmitted as an autosomal dominant trait. Its phenotypic and clinical expression is variable and involves several body systems. The ocular, skeletal and cardiovascular systems are characteristically affected. Involvement of the cardiovascular system is the main cause of morbidity and mortality. The authors report the case of a thirteen-year-old girl, with MFS diagnosed at age five, referred to the pediatric cardiology department because of mitral regurgitation. In addition to severe mitral regurgitation due to prolapse of both mitral valve leaflets, diagnostic exams showed massive mitral annulus calcification and ostium secundum atrial septal defect (ASD). The patient underwent successful mitral valve repair and ASD closure surgery. In this report we highlight some features of MFS, stressing the cardiovascular aspects.

Valsartan improves mitochondrial function in hearts submitted to acute ischemia.

The effect of valsartan, an angiotensin II-type I receptor blocker, on the mitochondrial function, was studied using an ex vivo animal model (hearts from Wistar rats), perfused in a Langendorff system and then submitted to global acute ischemia. Parameters evaluated were: membrane electrical potential (DeltaPsi, using a tetraphenylphosphonium-TPP+-electrode), oxygen consumption by the respiratory chain (Clark-type O2 electrode), phosphorylation lag phase (time necessary to phosphorylate a fixed amount of ADP) and ATP/ADP ratio (adenine nucleotides quantified by high-pressure liquid chromatography-HPLC). Valsartan acts preferentially in the phosphorylation, increasing ATP/ADP ratios (succinate: 1.6+/-0.4 versus 0.5+/-0.1--P<0.05; ascorbate/N,N,N',N'-tetramethyl-P-phenylenodiamine-TMPD: 1.1+/-0.2 versus 0.4+/-0.1--p<0.05 versus ischemia in the absence of valsartan) and decreasing lag phase (glutamate/malate: 50.0+/-9.6 s versus 127.2+/-19.03 s-84.6+/-16.2% versus 215.3+/-32.2%; P=0.01; succinate: 111.8+/-33.1 s versus 275.73+/-45.99 s-168.2+/-49.8% versus 414.9+/-69.2%; P=0.02 or ascorbate/TMPD: 11.0+/-3.9 s versus 62.4+/-11.63 s-34.9+/-12.4% versus 198.1+/-36.9%; P=0.001 versus ischemia in the absence of valsartan). This enables a higher energy production in hearts submitted to acute ischemia, for which having energy becomes critical to preserve mitochondrial function. These mechanisms allow us to better understand valsartan cytoprotection in ischemic cardiomyopathy.

Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria?

The cellular role of mitochondria includes ATP generation and the modulation of cytosolic calcium signals, besides being the "crossroads" for several cell death pathways. The maintenance of optimal mitochondrial functioning during the disease process increases the chances for survival. For example, ischaemia followed by reperfusion is known to negatively affect mitochondrial function, namely by inducing a deleterious condition called mitochondrial permeability transition (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately lead to cell death. Therefore, it seems important to protect mitochondrial function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist with antioxidant properties, has a positive impact on cardiac mitochondria during in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly, carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect mitochondria against the oxidative damage induced by the xanthine oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as an inhibitor of mitochondrial complex-I is also of importance, since this mitochondrial system was proposed as cause of the cardiotoxicity associated with the anti-neoplasic drug doxorubicin. This review points out the major findings concerning the positive impact of carvedilol on mitochondrial function and its use in the treatment of myocardial diseases where oxidative stress is known to be involved.

Protective effect of trimetazidine on myocardial mitochondrial function in an ex-vivo model of global myocardial ischemia.

Trimetazidine is an anti-ischemic drug whose cytoprotective mechanisms are not yet fully understood (but until now mainly related to the trimetazidine-induced "metabolic shift" from lipid beta-oxidation to glucose aerobic oxidation). We studied the effect of trimetazidine on the mitochondrial function of ischemic Wistar rat hearts perfused with glucose, using a model of ex-vivo perfusion (Langendorff system). We measured the electrical potential of the mitochondrial membrane, O2 consumption by the respiratory chain, energy charges generated and the enzyme activities of the respiratory chain complexes. In this model, trimetazidine had a preferential action on the oxidative system (mainly on complex I), increasing its enzyme activity and decreasing O2 consumption after phosphorylation; this could decrease oxygen free radical production and increase mitochondrial integrity, thus allowing the maintenance of the electrical potential. These results allow us to better understand the cytoprotective effects of trimetazidine in coronary artery disease.

Pyruvate improves mitochondrial bioenergetics in an ex-vivo animal model of myocardial ischemia.

Pyruvate is an energy substrate with known cardioprotective activity. We know now that this is due not only to its antioxidant activity, but also to its reduction of intracellular acidosis, modulation of intracytosolic calcium and improvement of cardiomyocyte contractility. However, the role of cardiac mitochondria in such positive effects has only recently begun to be understood and the exact mechanisms of the effect of pyruvate on mitochondria are still largely unknown. Aiming to study the effect of pyruvate on cardiac mitochondrial function during acute ischemia, we used an ex-vivo animal model, perfused in a Langendorff system and then subjected to ischemia in the presence and absence of pyruvate. We evaluated the mitochondrial membrane electrical potential, the respiratory chain O2 consumption (and respiratory control ratio) and the energy charges generated with different energy substrates. We conclude that pyruvate has some effect on the mitochondrial oxidative system (by non-significantly improving the respiratory control ratio), but its main action is on the phosphorylation system, significantly decreasing the time taken to complete a phosphorylation cycle (lag phase) and improving ATP production (increase in energy charge), thus allowing better maintenance of mitochondrial membrane structure, with consequent improvement of the electrical potential after a phosphorylation cycle. These findings have enabled better understanding of the mechanisms behind pyruvate cytoprotection in ischemic cardiomyopathy, clearly highlighting the essential role of cardiac mitochondria in this process.