| Autor: |
Prado NJ; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.; Institute of Medical and Experimental Biology of Cuyo, IMBECU-UNCuyo-CONICET, Mendoza 5500, Argentina., Muñoz EM; Laboratory of Neurobiology: Chronobiology Section, Institute of Histology and Embryology of Mendoza, IHEM-UNCUYO-CONICET, Mendoza 5500, Argentina., Farias Altamirano LE; Laboratory of Neurobiology: Chronobiology Section, Institute of Histology and Embryology of Mendoza, IHEM-UNCUYO-CONICET, Mendoza 5500, Argentina., Aguiar F; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.; Laboratory of Neurobiology: Chronobiology Section, Institute of Histology and Embryology of Mendoza, IHEM-UNCUYO-CONICET, Mendoza 5500, Argentina., Ponce Zumino AZ; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.; Institute of Medical and Experimental Biology of Cuyo, IMBECU-UNCuyo-CONICET, Mendoza 5500, Argentina., Sánchez FJ; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina., Miatello RM; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.; Institute of Medical and Experimental Biology of Cuyo, IMBECU-UNCuyo-CONICET, Mendoza 5500, Argentina., Pueyo E; BSICOS Group, I3A, IIS Aragón, University of Zaragoza, 50018 Zaragoza, Spain.; CIBER-BBN, 28029 Madrid, Spain., Diez ER; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.; Institute of Medical and Experimental Biology of Cuyo, IMBECU-UNCuyo-CONICET, Mendoza 5500, Argentina. |
| Abstrakt: |
Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA 2A , TNFα, nitrotyrosine, TGFβ, K ATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT 2 receptors, the MT 1 receptors, and SERCA 2A . Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of K ATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization. |
