Impaired oxidative metabolism and calcium mishandling underlie cardiac dysfunction in a rat model of post-acute isoproterenol-induced cardiomyopathy.

Autor:	Willis BC; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Salazar-Cantú A; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Silva-Platas C; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and., Fernández-Sada E; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Villegas CA; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Rios-Argaiz E; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, González-Serrano P; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Sánchez LA; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México;, Guerrero-Beltrán CE; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and., García N; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and., Torre-Amione G; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, Texas., García-Rivas GJ; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and., Altamirano J; Endowed Chair in Cardiology and Vascular Medicine, School of Medicine, Tecnológico de Monterrey, Monterrey México; Basic and Translational Research Center, Hospital Zambrano-Hellion, TEC Salud, San Pedro, Garza-García, México; and altamirano@itesm.mx.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2015 Mar 01; Vol. 308 (5), pp. H467-77. Date of Electronic Publication: 2014 Dec 19.
DOI:	10.1152/ajpheart.00734.2013
Abstrakt:	Stress-induced cardiomyopathy, triggered by acute catecholamine discharge, is a syndrome characterized by transient, apical ballooning linked to acute heart failure and ventricular arrhythmias. Rats receiving an acute isoproterenol (ISO) overdose (OV) suffer cardiac apex ischemia-reperfusion damage and arrhythmia, and then undergo cardiac remodeling and dysfunction. Nevertheless, the subcellular mechanisms underlying cardiac dysfunction after acute damage subsides are not thoroughly understood. To address this question, Wistar rats received a single ISO injection (67 mg/kg). We found in vivo moderate systolic and diastolic dysfunction at 2 wk post-ISO-OV; however, systolic dysfunction recovered after 4 wk, while diastolic dysfunction worsened. At 2 wk post-ISO-OV, cardiac function was assessed ex vivo, while mitochondrial oxidative metabolism and stress were assessed in vitro, and Ca(2+) handling in ventricular myocytes. These were complemented with sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), and RyR2 expression studies. Ex vivo, basal mechanical performance index (MPI) and oxygen consumption rate (MVO2) were unchanged. Nevertheless, upon increase of metabolic demand, by β-adrenergic stimulation (1-100 nM ISO), the MPI versus MVO2 relation decreased and shifted to the right, suggesting MPI and mitochondrial energy production uncoupling. Mitochondria showed decreased oxidative metabolism, membrane fragility, and enhanced oxidative stress. Myocytes presented systolic and diastolic Ca(2+) mishandling, and blunted response to ISO (100 nM), and all these without apparent changes in SERCA, PLB, or RyR2 expression. We suggest that post-ISO-OV mitochondrial dysfunction may underlie decreased cardiac contractility, mainly by depletion of ATP needed for myofilaments and Ca(2+) transport by SERCA, while exacerbated oxidative stress may enhance diastolic RyR2 activity. (Copyright © 2015 the American Physiological Society.)
Databáze:	MEDLINE
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