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1.
Int J Cardiol ; 164(2): 170-8, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21764470

RESUMO

BACKGROUND: Treatment of heart failure patients with aldosterone antagonists has been shown to reduce the occurrence of sudden cardiac death. Therefore we aimed at determining the consequences of chronic exposure to aldosterone and the aldosterone antagonists eplerenone and spironolactone on the electrophysiological properties of the heart in a rat model. METHODS AND RESULTS: Male Wistar rats were chronically treated (4weeks) with aldosterone (ALD) via an osmotic minipump. Spironolactone (SPI) or eplerenone (EPL) was administered with the rat chow. ALD treated animals developed left ventricular hypertrophy, prolonged QT-intervals, a higher rate of ventricular premature beats and non-sustained ventricular tachycardia despite normal blood pressure values. Spironolactone and eplerenone were both able to inhibit the alterations. Left-ventricular mRNA expressions of Kv4.2 and Kv4.3 (Ito), Kv1.5 (IKur), Kir2.1 and Kir2.3 (IK1) and of Cav1.2 (L-type Ca(2+) channel) were significantly down-regulated in ALD. Correspondingly, the protein expressions of subunits Kv1.5, Kir2.3 and Cav1.2 were significantly decreased. A diminished calcineurin activity and mRNA expression of the Aß subunit of calcineurin were found in ALD, which was insensitive to aldosterone antagonists. CONCLUSIONS: Chronic aldosterone-overload induces blood pressure independent structural and electrical remodeling of the myocardium resulting in an increased risk for malignant ventricular arrhythmias.


Assuntos
Aldosterona/toxicidade , Hipertensão/fisiopatologia , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/fisiopatologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Animais , Masculino , Ratos , Ratos Wistar
2.
Eur J Cardiothorac Surg ; 41(6): 1225-32, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22219473

RESUMO

OBJECTIVE: Patients undergoing transapical aortic valve implantation (TA-AVI) are usually over 80 years old and have a high prevalence of chronic kidney disease. However, transcatheter valve therapies require the use of contrast injections with the risk of nephrotoxicity. The aim of this study was to evaluate post-operative kidney function and survival in patients with pre-existing renal impairment with regard to the amount of contrast media used during TA-AVI. METHODS: From January 2008 to March 2011, 50 patients (52% females, mean age 80.7 ± 5.3 years) with a serum creatinine level of >1.3 mg/dl were investigated. Patients receiving a dose of <100 ml of a contrast agent (low-dose group, n = 24) were separated from those who received >100 ml of a contrast agent (high-dose group, n = 26). An acute contrast-induced nephropathy (CIN) was defined as a serum creatinine increase of 0.5 mg/dl or by >25% of a baseline value within 48 h from contrast medium administration. Patients in both groups had similar characteristics in terms of age, sex, body mass index and comorbidities. RESULTS: The median pre-contrast creatinine was 1.67 (1.37-1.83) mg/dl in the low-dose group and 1.51 (1.26-1.98) mg/dl in the high-dose group (P = 0.76). The post-contrast creatinine at 48 h was 1.53 (1.33-2.05) and 2.29 (1.67-2.86) mg/dl in the groups receiving low- and high-dose contrast agents, respectively (P = 0.007). CIN occurred in 41.7% (n = 10) of patients in the low-dose contrast group and in 69.2% (n = 18) in the high-dose contrast group (P = 0.046). Haemodialysis is necessary for 16.7% of the low-dose group and 38.5% of the high-dose group (P = 0.12). Trends towards longer intensive care unit and hospital stay were seen in patients with an extensive use of contrast media [4.3 (2.5-6.5) vs. 5 (3-7.8) days and 12 (9-14.3) vs. 13 (9-18) days, P = 0.091 vs. P = 0.546, respectively]. Regarding death, 3-month and 3-year mortality were significantly higher in the high-dose group (8.3 vs. 30.8%, P = 0.036 and 25 vs. 61.5%, P = 0.004, respectively). CONCLUSIONS: Our results indicate a possible association between higher CIN and mortality rate and the extensive use of contrast media during TA-AVI among high-risk patients with pre-existing renal impairment.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Meios de Contraste/administração & dosagem , Implante de Prótese de Valva Cardíaca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Biomarcadores/sangue , Meios de Contraste/efeitos adversos , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Radiografia , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Análise de Sobrevida
3.
Transplantation ; 87(5): 726-33, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19295318

RESUMO

BACKGROUND: Calcineurin-inhibitor-(CNI)-induced renal failure is one major cause of morbidity in cardiac transplantation (HTx). In this prospective, randomized, multicenter trial, the impact of immunosuppressive conversion toward CNI-free (mycophenolate mofetil [MMF] and sirolimus) or a CNI-reduced immunosuppressive regimen on renal function, efficacy, and safety was evaluated. METHODS: Since 2004, 63 HTx-patients (0.5-18.4 years after HTx) with CNI-based immunosuppression and reduced creatinine clearance less than 60 mL/min (39+/-15 mL/min) were included in this trial. Patients in the CNI-free-Group (group 1) were converted to sirolimus that was started with 2 mg/day until target trough levels (8-14 ng/mL) were achieved. Subsequently, CNIs were withdrawn. In CNI-reduction-Group (group 2), CNI target trough levels were reduced by 40%. In both groups MMF was continued and trough level adjusted (1.5-4 microg/mL). RESULTS: Patients demographics and survival (mean follow-up time: 16.7+/-9 months) was equal (100%). Renal function improved significantly after complete CNI withdrawal while remaining unchanged with CNI-reduction (Creatinine clearance after 12 months: 53+/-24 mg/dL [group 1] vs. 38+/-20 mg/dL [group 2], P=0.01). End-stage renal failure (hemodialysis) was avoided by CNI-withdrawal and occurred only after CNI reduction (n=6; P=0.01). Acute rejection episodes were more common in group 2 (4 vs. 2). Graft function remained stable (echocardiography) within both groups. Adverse events were more common in group 1 (65%) than in group 2 (n=40%) and were responsible for discontinuation in 4 and 0 cases, respectively. CONCLUSIONS: Conversion toward a CNI-free immunosuppression (Mycophenolate, sirolimus) is superior to CNI-reduced immunosuppression in improving renal failure in late HTx-recipients. However, this benefit is relativized by the increased incidence and severity of sirolimus/MMF-associated side effects.


Assuntos
Transplante de Coração/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/imunologia , Rim/imunologia , Ácido Micofenólico/análogos & derivados , Sirolimo/uso terapêutico , Adulto , Idoso , Inibidores de Calcineurina , Feminino , Humanos , Rim/efeitos dos fármacos , Falência Renal Crônica/complicações , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Seleção de Pacientes
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