Prolonged cardiac dysfunction after withdrawal of chronic cocaine exposure in rats.
Cocaine abuse causes myocardial dysfunction and induces oxidative stress. However, the reversibility of these effects is unknown. We evaluated myocardial function and oxidative stress after cocaine withdrawal, in a rat model of chronic cocaine exposure. Standard echocardiography and Doppler tissue imaging were performed after 4 weeks (W4) of cocaine administration (2 x 7.5 mg/kg/d, i.p.) and 4 weeks after interruption (W8). At these time points, redox state (reduced glutathione GSH, oxidized glutathione GSH, and GSH/GSSG) as well as activities of GSH peroxidase (GPX), superoxide dismutase (SOD), and catalase were determined in the left ventricle (LV). At W4, LV fractional shortening, posterior wall thickening, systolic myocardial ventricular gradient (SMVG), dP/dt(max), and dp/dt(min) were decreased, compared with control values while LV myocardial thickness was increased. At W8, even though dP/dtmax and dp/dt(min) were restored, myocardial function was still impaired as demonstrated by the decrease in posterior wall thickening, and systolic myocardial velocity gradient. At W4, CAT and GPX activities as well as GSH/GSSG ratio were reduced while SOD activity was increased. Antioxidant markers and redox ratio remained altered 4 weeks after the last injection. Thus, these data demonstrate the persistence of LV dysfunction after cocaine withdrawal, which occurs in a context of a deficit in antioxidant defenses.
INSERM E 9920, IFRMP no. 23, University Medical School, Rouen, France.
Fabienne
F
Moritz
Christelle
C
Monteil
Paul
P
Mulder
Geneviève
G
Derumeaux
Catherine
C
Bizet
Sylvanie
S
Renet
Françoise
F
Lallemand
Vincent
V
Richard
Christian
C
Thuillez
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects*; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
D000975:Antioxidants; D003042:Cocaine