Document Detail

Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide.
MedLine Citation:
PMID:  21247774     Owner:  NLM     Status:  Publisher    
Objective: Levosimendan has been reported to exert cardioprotection. In this study, we have examined the cardiac effects of different doses of intracoronary levosimendan on ischemia/reperfusion injuries, and the involvement of K(ATP) channels and nitric oxide (NO). Methods: The experiments were performed in a total of 56 anesthetized pigs. In 21 pigs, 1.5, 5 and 12μgmin(-1) levosimendan was infused over 15min into the coronary artery at the onset of 1h reperfusion following 2-h ischemia and the effects on cardiac function, infarcted area, and on apoptosis/autophagy were examined. In addition, the activation of Akt and extracellular receptor kinase (ERK) was analyzed. The findings were compared with those obtained in a further 14 pigs where the highest dose levosimendan was infused after glibenclamide and l-nitro-arginine methyl ester (l-NAME). Results: Intracoronary 1.5, 5 and 12μgmin(-1) levosimendan caused an increase of segmental shortening, dP/dt(max) and cardiac output of 7.8%, 22.6%, and 31.6%; 7.6%, 16.9%, and 21.6%; 2.8%, 5.9%, and 6.2%, respectively, from values measured at the end of ischemia. The beneficial effects elicited by levosimendan were still evident at the end of reperfusion when the increase of segmental shortening, dP/dt(max) and cardiac output caused by the three doses of levosimendan amounted to 3.7%, 13.3%, and 16.5%; 1.5%, 9.4%, and 11%; 1.4%, 2.7%, and 3.9%, respectively. When doses of 5 and 12μgmin(-1) levosimendan were used, a reduction of infarcted area to about 69% and 67% of area at risk was observed, and was significantly different from that of about 79% measured in control animals. In addition, after intracoronary levosimendan, the inhibition of apoptosis and activation of autophagy and a dose-related increase of the level of phosphorylation of ERK and Akt were observed. These responses were completely prevented by glibenclamide and significantly reduced by l-NAME. Conclusions: The results of this study show that intracoronary levosimendan reduces cell death induced by ischemia/reperfusion in a dose-dependent manner and activates survival signaling through K(ATP) channel opening and NO. These findings support interesting implications for cardioprotection in interventional cardiology and cardiac surgery.
Philippe Primo Caimmi; Claudio Molinari; Francesca Uberti; Ezio Micalizzi; Guido Valente; David A S G Mary; Giovanni Vacca; Elena Grossini
Related Documents :
17467434 - A classification system for the bicuspid aortic valve from 304 surgical specimens.
3882814 - Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy.
1945764 - Performance of the isolated, ejecting heart: effects of aortic impedance and exogenous ...
1989824 - Total left main coronary artery occlusion after aortic aneurysm repair and valve replac...
17765644 - Residual high-grade angina after enhanced external counterpulsation therapy.
10207174 - Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 ...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-17
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  -     ISSN:  1873-734X     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Department of Cardiac Surgery, Azienda Ospedaliera Universitaria Maggiore della Carità and University of East Piedmont "A. Avogadro", corso Mazzini 18, 28100, Novara, Italy; Laboratory of Physiology and Experimental Surgery, Azienda Ospedaliera Universitaria Maggiore della Carità and University of East Piedmont "A. Avogadro", corso Mazzini 18, 28100, Novara, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Outcome after surgery for acute aortic dissection type A in patients over 70 years: data analysis fr...
Next Document:  Positive cultures from cardiopulmonary bypass: prevalence and relevance regarding postoperative infe...