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First published online on January 11, 2006.
Experimental Physiology (2006)
DOI: 10.1113/expphysiol.2005.032557
© The Physiological Society 2006

A more recent version of this article appeared on March 1, 2006
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Received October 9, 2005
Revised November 7, 2005
Accepted after revision January 9, 2006


Heart/Cardiac Muscle [240]

REMOTE MYOCARDIUM GENE EXPRESSION AFTER 30 AND 120 MINUTES OF ISCHEMIA IN THE RAT

Miguel S Guerra 1, Roberto Roncon-Albuquerque Jr 2, André P Lourenço 1, Inês Falcão-Pires 1, Paulo Cibrão-Coutinho 1, Adelino F Leite-Moreira 1*

1 Department of Physiology, Faculty of Medicine of Porto
2 Faculty of Medicine of Porto

* To whom correspondence should be addressed. E-mail: amoreira{at}med.up.pt.


   Abstract
We examined biventricular function and remote myocardium gene expression changes taking place during acute myocardial ischemia. Wistar rats (n=27) were randomly assigned to: LCA ligation during 30 or 120min; and sham. Evans-blue infusion revealed antero-apical LV and left IV-septal ischemia (35.5±0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, BNP was upregulated in the LV at 30min (+370±191%) and 120min (+221±112%) whilst in the RV it was only significant at 120min (+128±39%). HIF-1{alpha} and IL-6 overexpression positively correlated with BNP. iNOS upregulation was present in both ventricles at 120min (LV:+3271±95%; RV:+311±122%), but only in the RV at 30min (+256±88%). IGF-1 increased in both ventricles at 30min (RV: +59±18%; LV:+567±192%) and 120min (RV:+69±33%; LV:+120±24%). ppET-1 was upregulated in the RV at 120min (+77±25%). Ca2+-handling proteins were selectively changed in the LV at 120min (SERCA2a:-53±7%; Phospholambam:+31±4%; NCX:-31±6%), while NHE was altered only in the RV (-79±5%, 30min; +155±70%, 120min). TNF-{alpha} and ACE were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction of those observed in heart failure.

Key Words: Gene expression, Ischaemia, Myocardium







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