Résumé
Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients.
Sujets)
Humains , Maladie de Parkinson/métabolisme , Canaux calciques/métabolisme , Calcium/métabolisme , Cardiopathies/traitement médicamenteux , Maladie de Parkinson/complications , Maladie de Parkinson/anatomopathologie , Canaux calciques/usage thérapeutique , Cardiopathies/étiologie , Homéostasie/physiologieSujets)
Prévention des Maladies , Stress oxydatif , Radicaux libres/métabolisme , Radicaux libres/toxicité , Apports nutritionnels recommandés/tendances , Antioxydants/pharmacocinétique , Antioxydants/usage thérapeutique , Oxydants/antagonistes et inhibiteurs , Oxydants/effets indésirables , Oxydants/toxicitéRésumé
La terapia por quelacion consiste en el uso de aminoacidos no esenciales, para eliminar del organismo iones minerales, principalmente los denominados metales pesados; siendo un importante auxiliar terapeutico en el control de procesos isquemicos, enfermedades degenerativas cronicas, envejecimiento y el cancer. Se revisaron los conceptos cientificos que la consolidan, asi como se analizaron los estudios empiricos publicados, principalmente por parte del autor
Sujets)
Acides aminés/usage thérapeutique , Chélateurs , Maladie chronique/thérapie , Ions/effets indésirables , Bolivie , Radicaux libresRésumé
Parece existir uma relaçäo causal entre radicais livres e isquemia por reperfusäo tissular, referente ao processo hipóxia-reoxigenbaçäo. É apresentada uma revisäo da bioquímica dos radicais libres e dos estudos demonstrativos de que estas moléculas constituem fator causal da isquemia
Sujets)
Radicaux libres , Infarctus du myocarde/étiologie , Lésion de reperfusion myocardique/induit chimiquementRésumé
La participación de los Radicales libres (RL) en la génesis de los procesos isquémicos por reperfusión, ha adquirido amplia notoriedad en los últimos tiempos, habiendo, las recientes investigaciones, demostrado que, la reoxigenación del miocardio en hipoxia, determina un aumento de tejido lesionado. Existen evidencias que sugieren la participación de los RL, en forma total o parcial, en la producción de lesión microvascular de las células parenquimatosas en los tejidos isquemiados, a través del proceso hipoxia reoxiganación