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Experimental Physiology 91.2 pp 473-480
DOI: 10.1113/expphysiol.2005.032557
© The Physiological Society 2006
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Remote myocardium gene expression after 30 and 120 min of ischaemia in the rat

Miguel S. Guerra1,*, Roberto Roncon-Albuquerque, Jr1,*, André P. Lourenço1, Inês Falcão-Pires1, Paulo Cibrão-Coutinho1 and Adelino F. Leite-Moreira1

1 Department of Physiology, Faculty of Medicine, University of Porto, Portugal

The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n= 27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5 ± 0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370 ± 191%) and 120 min (+221 ± 112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128 ± 39%). Hipoxia-inducible factor 1{alpha} and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327 ± 195%; RV, +311 ± 122%), but only in the RV at 30 min (+256 ± 88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59 ± 18%; LV, +567 ± 192%) and 120 min (RV, +69 ± 33%; LV, +120 ± 24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77 ± 25%). Ca2+-handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53 ± 7%; phospholamban, +31 ± 4%; Na+–Ca2+ exchanger, 31 ± 6%), while Na+–H+ exchanger was altered only in the RV (–79 ± 5%, 30 min; +155 ± 70%, 120 min). Tumour necrosis factor-{alpha} and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure.

(Received 20 December 2005; accepted after revision 9 January 2006; first published online 11 January 2006)
Corresponding author A. F. Leite-Moreira: Department of Physiology, Faculty of Medicine, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal. Email: amoreira{at}med.up.pt


*Miguel S. Guerra and Roberto Roncon-Albuquerque Jr contributed equally to this work.







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