TY - JOUR
T1 - Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart
AU - Ibacache, Mauricio
AU - Sanchez, Gina
AU - Pedrozo, Zully
AU - Galvez, Felipe
AU - Humeres, Claudio
AU - Echevarria, Ghislaine
AU - Duaso, Juan
AU - Hassi, Mario
AU - Garcia, Lorena
AU - Díaz-Araya, Guillermo
AU - Lavandero, Sergio
N1 - Funding Information:
This work was supported by Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT ): Grant 1080497 (G.S.), Grant 1110346 (L.G; S.L), Postdoctoral Fellowship 3110039 (Z.P). and Fondo de Investigación Avanzada en Areas Prioritarias (FONDAP ) Grant: 15010006 (G.S., S.L.), and the Comisión Nacional de Investigación Cientifica y Tecnologica (CONICYT), Santiago, Chile .
PY - 2012/4
Y1 - 2012/4
N2 - Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α 2-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30min of regional ischemia followed by 120min of reperfusion with dexmedetomidine before ischemia. The α 2-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of α 2-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and peri-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of α 2-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine peri-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac α 2-adrenergic receptor stimulation.
AB - Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α 2-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30min of regional ischemia followed by 120min of reperfusion with dexmedetomidine before ischemia. The α 2-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of α 2-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and peri-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of α 2-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine peri-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac α 2-adrenergic receptor stimulation.
KW - Alpha2-adrenergic receptor
KW - Anesthesia
KW - Dexmedetomidine
KW - Myocardial infarction
KW - Myocardial ischemia
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U2 - 10.1016/j.bbadis.2011.12.013
DO - 10.1016/j.bbadis.2011.12.013
M3 - Article
C2 - 22230708
AN - SCOPUS:84856285460
SN - 0925-4439
VL - 1822
SP - 537
EP - 545
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 4
ER -