RESUMO
Epidemiological data show a rise in the mean age of patients affected by heart disease undergoing cardiac surgery. Senescent myocardium reduces the tolerance to ischemic stress and there are indications about age-associated deficit in post-operative cardiac performance. Coenzyme Q10 (CoQ10), and more specifically its reduced form ubiquinol (QH), improve several conditions related to bioenergetic deficit or increased exposure to oxidative stress. This trial (Eudra-CT 2009-015826-13) evaluated the clinical and biochemical effects of ubiquinol in 50 elderly patients affected by severe aortic stenosis undergoing aortic valve replacement and randomized to either placebo or 400 mg/day ubiquinol from 7 days before to 5 days after surgery. Plasma and cardiac tissue CoQ10 levels and oxidative status, circulating troponin I, CK-MB (primary endpoints), IL-6 and S100B were assessed. Moreover, main cardiac adverse effects, NYHA class, contractility and myocardial hypertrophy (secondary endpoints) were evaluated during a 6-month follow-up visit. Ubiquinol treatment counteracted the post-operative plasma CoQ10 decline (p<0.0001) and oxidation (p=0.038) and curbed the post-operative increase in troponin I (QH, 1.90 [1.47-2.48] ng/dL; placebo, 4.03 [2.45-6.63] ng/dL; p=0.007) related to cardiac surgery. Moreover, ubiquinol prevented the adverse outcomes that might have been associated with defective left ventricular ejection fraction recovery in elderly patients.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Complicações Pós-Operatórias/prevenção & controle , Ubiquinona/análogos & derivados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Ubiquinona/metabolismo , Ubiquinona/uso terapêuticoRESUMO
Chronic hyperglycemia is closely associated with impaired substrate metabolism, dysregulated mitochondrial membrane potential, and apoptosis in the diabetic heart. As adult cardiomyocytes display a limited capacity to regenerate following an insult, it is essential to protect the myocardium against the detrimental effects of chronic hyperglycemia. This study therefore investigated whether phenylpyruvic acid-2-O-ß-D-glucoside, present in Aspalathus linearis (rooibos), is able to attenuate hyperglycemia-induced damage in H9c2 cardiomyocytes. H9c2 cardiomyocytes were exposed to a high glucose concentration (33 mM) prior to treatment with phenylpyruvic acid-2-O-ß-D-glucoside (1 µM), metformin (1 µM), or a combination of phenylpyruvic acid-2-O-ß-D-glucoside and metformin (both at 1 µM). Our data revealed that high glucose exposure increased cardiac free fatty acid uptake and oxidation, mitochondrial membrane potential, and apoptosis (caspase 3/7 activity and TUNEL), and decreased the Bcl2/Bax protein expression ratio. Phenylpyruvic acid-2-O-ß-D-glucoside treatment, alone or in combination with metformin, attenuated these glucose-induced perturbations, confirming its protective effect in H9c2 cardiomyocytes exposed to chronic hyperglycemia.