Document Detail


The protective effect of fasudil pretreatment combined with ischemia postconditioning on myocardial ischemia/reperfusion injury in rats.
MedLine Citation:
PMID:  25317813     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVE: Ischemic postconditioning (IPO) and pharmacological pretreatment may reduce myocardial necrosis and apoptosis during ischemia/reperfusion. This study aimed to determine the protective effect of fasudil pretreatment combined with IPO on myocardial ischemia/reperfusion injury in rats and explore the possible mechanisms.
MATERIALS AND METHODS: The SD rats were induced by intraperitoneal injection of fasudil hydrochloride (1 or 10 mg/kg) 60 min before the initiation of ischemia, while the control rats were given the same volume of saline. The hearts were hung on the Langendorff perfusion apparatus and underwent 30 min global ischemia and 120 min reperfusion. The IPO protocol was induced by six cycles of 10 sec ischemia and 10 sec reperfusion at the onset of reperfusion. The hemodynamic changes were measured, myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining, cardiomyocyte apoptosis was detected by TUNEL staining, lactate dehydrogenase (LDH) was analyzed from coronary effluents, phosphorylation of Akt and eNOS, as well as expression of Bcl-2 and Bax were measured by western blotting analysis.
RESULTS: The high-dose fasudil (10 mg/kg) pretreatment group and IPO group significantly improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the control group (p < 0.05). In addition, the high-dose fasudil pretreatment combined with IPO group could further improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the single treatment groups (p < 0.05).
CONCLUSIONS: The combination of high-dose fasudil pretreatment and IPO had a synergistic protective effect on myocardial ischemia/reperfusion injury, which was mediated via upregulating the PI3K/Akt/eNOS pathway, increasing expression of antiapoptotic Bcl-2, and decreasing expression of proapoptotic Bax.
Authors:
W-N Li; N Wu; W-Q Shu; Y-E Guan; D-L Jia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European review for medical and pharmacological sciences     Volume:  18     ISSN:  2284-0729     ISO Abbreviation:  Eur Rev Med Pharmacol Sci     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-10-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9717360     Medline TA:  Eur Rev Med Pharmacol Sci     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  2748-58     Citation Subset:  IM    
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