Document Detail


The cardio-protective properties of Ncx-6550, a nitric oxide donating pravastatin, in the mouse.
MedLine Citation:
PMID:  20690980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Determine the cardio-protective properties of a nitric oxide-releasing pravastatin (Ncx-6550), in comparison to pravastatin.
METHODS: A mouse model of myocardial infarct was used assessing tissue damage both at 2 and 24 hour post-reperfusion, administering compounds both prophylactically and therapeutically.
RESULTS: Ncx-6550 induced a significant dose-dependent (2.24-22.4 micromol/kg i.p.) cardioprotection in the two hour reperfusion protocol. In vehicle-treated mice, infarct size (expressed as fraction of area at risk; IS/AR) was 41.2 +/- 1%, and it was reduced to 22.2 +/- 0.9% and 32.6 +/- 0.9% following 22.4 and 6.72 micromol/kg Ncx-6550 (p < 0.05). 22.4 micromol/kg Ncx-6550 also increased cardiac levels of the enzyme heme oxygenase-1. Treatment of mice with pravastatin induced significant reduction of myocardial injury only at 22.4 micromol/kg (IS/AR value: 33.7 +/- 0.9%). In a 24 hour reperfusion protocol, Ncx-6550 and pravastatin were tested only at 22.4 micromol/kg i.p. being given either one hour prior to ischemia (prophylactic protocol) or one hour into reperfusion (therapeutic protocol). With either treatment scheme, Ncx-6550 produced higher cardioprotection compared to pravastatin, as reflected also by a reduction in the incidence of lethality as well as in circulating troponin I and interleukin-1beta levels.
CONCLUSIONS: These results indicate Ncx-6550 as a novel therapeutic agent with a potential for the treatment of myocardial infarct.
Authors:
Clara Di Filippo; Angela Monopoli; Ennio Ongini; Mauro Perretti; Michele D'Amico
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Microcirculation (New York, N.Y. : 1994)     Volume:  17     ISSN:  1549-8719     ISO Abbreviation:  Microcirculation     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-09     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434935     Medline TA:  Microcirculation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  417-26     Citation Subset:  IM    
Affiliation:
Department of Experimental Medicine, Section of Pharmacology, 2nd University of Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiotonic Agents / pharmacokinetics,  pharmacology*
Heme Oxygenase-1 / metabolism
Hemodynamics / drug effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics,  pharmacology*
Interleukin-1beta / blood
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction / pathology,  physiopathology,  prevention & control
Myocardial Reperfusion Injury / drug therapy,  pathology,  physiopathology
Nitrates / blood,  pharmacokinetics,  pharmacology*
Nitric Oxide Donors / pharmacokinetics,  pharmacology*
Nitrites / blood
Pravastatin / analogs & derivatives*,  pharmacokinetics,  pharmacology
Troponin I / blood
Chemical
Reg. No./Substance:
0/1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthaleneheptanoic acid 4-(nitrooxy)butyl ester; 0/Cardiotonic Agents; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Interleukin-1beta; 0/Nitrates; 0/Nitric Oxide Donors; 0/Nitrites; 0/Troponin I; 81093-37-0/Pravastatin; EC 1.14.99.3/Heme Oxygenase-1

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