Access to the PDF text

Free Article !

Archives of cardiovascular diseases
Volume 102, n° S1
page 31 (mars 2009)
Doi : 10.1016/S1875-2136(09)72200-4
Themes et posters

C013 Cocaine-induced LV diastolic impairment is associated with cardiac mitochondrial dysfunction and ROS production: role of nadph and xanthine oxidase

A. Vergeade 1, P. Mulder 1, C. Dehaudt 1, D. Fortin 2, R. Ventura-Clapier 2, C. Thuillez 1, C. Monteil 1
1 Inserm U644, Rouen, France 
2 Inserm U769, Chatenay-Malabry, France 


Recent studies show that long-term cocaine use induces diastolic impairment. This functional effect may be linked to cocainetriggered biochemical responses such as oxidative stress. Indeed, previously we have demonstrated that myocardial NADPH and xanthine oxidase (XO) contribute to ROS generation in cocainetreated rats. In the current study, we hypothesized that cocaineinduced ROS production could induce mitochondrial damage that in turn might participate in ventricular diastolic dysfunction. Wistar rats were treated with cocaine alone (2×7.5mg/kg/day, IP) or with a NOX inhibitor (apocynin, 50mg/kg/day, po) or a XO inhibitor (allopurinol, 50mg/kg/day, po). These groups were compared to control rats (saline solution, IP). After 7 days, LV pressure-volume signals were acquired. Oxygen consumption was measured in situ on permeabilized cardiac fibers isolated from the LV. ROS production was measured using electron paramagnetic resonance in both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria. Our results show that cocaine-induced cardiac dysfunction is characterized by a diastolic impairment. Indeed cocaine induces an increase of Tau, an index of LV relaxation and of end-diastolic pressure volume relation (+80 % and +171 % respectively, p<0.05). Both apocynin and allopurinol were able to improve ventricular relaxation. Further, we found that cocaine increased oxygen consumption in mitochondria specifically through complex I (+34 %, p<0.05) and complex III (+120 %, p<0.05) whereas ATP production was decreased. Moreover, ROS level increased only in IFM from cocaine rats (+74 %, p<0.05). In contrast, apocynin or allopurinol treatments prevented the rise in ROS levels and prevented the mitochondrial respiratory chain alterations. In conclusion, this work shows that cocaine-induced LV diastolic impairment is associated with a specific mitochondrial dysfunction. An increase in ROS production via NADPH and XO induces a mitochondrial dysfunction which in turn contributes to the development of oxidative stress and ventricular diastolic dysfunction.

The full text of this article is available in PDF format.
The full text of this article is available in PDF format.
Click here to see it.

Top of the page

© 2009  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Article Outline
You can move this window by clicking on the headline