2026-04-27T01:59:25Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/179582024-09-27T08:02:02Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc García-Prieto, Jaime author García-Ruiz, Jose Manuel author Sanz-Rosa, David author Pun, Andrés author García-Alvarez, Ana author Davidson, Sean M author Fernández-Friera, Leticia author Nuno-Ayala, Mario author Fernández-Jiménez, Rodrigo author Bernal, Juan A author Izquierdo-Garcia, José Luis author Jimenez-Borreguero, Jesús author Pizarro, Gonzalo author Ruiz-Cabello, Jesús author Macaya, Carlos author Fuster, Valentín author Yellon, Derek M author Ibáñez, Borja author 2014-07 Selective stimulation of β3 adrenergic-receptor (β3AR) has been shown to reduce infarct size in a mouse model of myocardial ischemia/reperfusion. However, its functional long-term effect and the cardioprotective mechanisms at the level of cardiomyocytes have not been elucidated, and the impact of β3AR stimulation has not been evaluated in a more translational large animal model. This study aimed at evaluating pre-perfusion administration of BRL37344 both in small and large animal models of myocardial ischemia/reperfusion. Pre-reperfusion administration of the β3AR agonist BRL37344 (5 μg/kg) reduced infarct size at 2-and 24-h reperfusion in wild-type mice. Long-term (12-weeks) left ventricular (LV) function assessed by echocardiography and cardiac magnetic resonance (CMR) was significantly improved in β3AR agonist-treated mice. Incubation with β3AR agonist (BRL37344, 7 μmol/L) significantly reduced cell death in isolated adult mouse cardiomyocytes during hypoxia/reoxygenation and decreased susceptibility to deleterious opening of the mitochondrial permeability transition pore (mPTP), via a mechanism dependent on the Akt-NO signaling pathway. Pre-reperfusion BRL37344 administration had no effect on infarct size in cyclophilin-D KO mice, further implicating mPTP in the mechanism of protection. Large-white pigs underwent percutaneous coronary ischemia/reperfusion and 3-T CMR at 7 and 45 days post-infarction. Pre-perfusion administration of BRL37344 (5 μg/kg) decreased infarct size and improved long-term LV contractile function. A single-dose administration of β3AR agonist before reperfusion decreased infarct size and resulted in a consistent and long-term improvement in cardiac function, both in small and large animal models of myocardial ischemia/reperfusion. This protection appears to be executed through inhibition of mPTP opening in cardiomyocytes. Basic Res Cardiol . 2014 Jul;109(4):422. http://hdl.handle.net/20.500.12105/17958 24951958 10.1007/s00395-014-0422-0 1435-1803 Basic research in cardiology β3 adrenergic receptor selective stimulation during ischemia/reperfusion improves cardiac function in translational models through inhibition of mPTP opening in cardiomyocytes.