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Ischemic Postconditioning Reduces Reperfusion Arrhythmias by Adenosine Receptors and Protein Kinase C Activation but Is Independent of KATP Channels or Connexin 43.
Diez, Emiliano Raúl; Sánchez, Jose Antonio; Prado, Natalia Jorgelina; Ponce Zumino, Amira Zulma; García-Dorado, David; Miatello, Roberto Miguel; Rodríguez-Sinovas, Antonio.
Afiliação
  • Diez ER; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
  • Sánchez JA; Institute of Medical and Experimental Biology of Cuyo, CONICET, Mendoza 5500, Argentina.
  • Prado NJ; Cardiovascular Diseases Research Group, Department of Cardiology, Vall d'Hebron University Hospital and Research Institute, Universitat Autònoma de Barcelona, Departament de Medicina, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
  • Ponce Zumino AZ; Centro de Investigación Biomédica en Red sobre Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain.
  • García-Dorado D; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
  • Miatello RM; Institute of Medical and Experimental Biology of Cuyo, CONICET, Mendoza 5500, Argentina.
  • Rodríguez-Sinovas A; Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
Int J Mol Sci ; 20(23)2019 Nov 25.
Article em En | MEDLINE | ID: mdl-31775376
Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A1, A2A and A3 receptors, protein kinase C, ATP-dependent potassium (KATP) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A1, A2A and A3 receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a KATP inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Proteína Quinase C / Isquemia Miocárdica / Receptores Purinérgicos P1 / Conexina 43 / Canais KATP / Pós-Condicionamento Isquêmico Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Proteína Quinase C / Isquemia Miocárdica / Receptores Purinérgicos P1 / Conexina 43 / Canais KATP / Pós-Condicionamento Isquêmico Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Argentina País de publicação: Suíça