Une étude sur ncx6550 vient d'être mise en ligne aujourd'hui et va
paraitre dans le magazine " Microcirculation ". MONSIEUR Ongini en
personne a collaboré pour cette étude prometteuse !!
The cardio-protective properties of NCX-6550, a nitric oxide donating
pravastatin, in the mouse
Clara Di Filippo 1 , Angela Monopoli 2 , Ennio Ongini 2 , Mauro Perretti
3 and Michele D'Amico 1
1 Department of Experimental Medicine, Section of Pharmacology, 2nd
University of Naples, Italy
2 NicOx Research Institute, Via Ariosto, 21, Bresso, Italy
3 The William Harvey Research Institute, Barts and the London School
of Medicine, Queen Mary University of London, Charterhouse Square,
London, EC1M 6BQ, United Kingdom
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 h post-reperfusion, administering compounds both
prophylactically and therapeutically.
Results: NCX-6550 induced a significant dose-dependent (2.24-22.4
μmol/kg ip) cardioprotection in the 2h 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 μmol/kg NCX-6550 (P<0.05). 22.4
μmol/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 μmol/kg (IS/AR
value: 33.7±0.9%). In a 24h reperfusion protocol, NCX-6550 and
pravastatin were tested only at 22.4 μmol/kg i.p., being given
either 1h prior to ischemia (prophylactic protocol) or 1h 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-1β levels.
Conclusions: These results indicate NCX-6550 as a novel therapeutic
agent with a potential for the treatment of myocardial infarct.