Improved post-myocardial infarction survival with probucol in rats: effects on left ventricular function, morphology, cardiac oxidative stress and cytokine expression.
OBJECTIVE
The goal of this study was to evaluate whether reducing the potentially deleterious effects of oxidative stress with the potent anti-oxidant probucol improves prognosis after myocardial infarction (MI) in rats.


BACKGROUND
Oxidative stress has been documented in patients early and late after MI, particularly when it is associated with congestive heart failure.


METHODS
Rats surviving acute MIs for 24 h (n = 247) were assigned to vehicle or probucol (61 mg/kg, daily) for four weeks, at which time cardiac hemodynamic, morphologic and molecular measurements were done.


RESULTS
In rats with large MIs, probucol improved survival (87.9%) when compared with vehicle (50.6%) (p < 0.001). Probucol also partially preserved left ventricular (LV) systolic but not diastolic function. Probucol increased scar thickness and decreased cardiac fibrosis but did not modify LV hypertrophy or dilation. Finally, probucol decreased cardiac oxidative stress, as assessed by measuring cardiac malondialdehydes, and decreased the cardiac expression of the pro-inflammatory cytokines interleukin (IL)-1beta and IL-6 but did not modify fetal gene re-expression in rats with large MIs.


CONCLUSIONS
This study indicates that the anti-oxidant probucol markedly improves post-MI survival in rats despite few demonstrable effects on cardiac remodeling or hemodynamics. Its beneficial effects may, however, be associated with reduced cardiac fibrosis, oxidative stress and expression of pro-inflammatory cytokines.
Sia
Ying Tung
YT
Department of Medicine, Montreal Heart Institute, Montreal, Canada.
Parker
Thomas G
TG
Liu
Peter
P
Tsoporis
James N
JN
Adam
Albert
A
Rouleau
Jean L
JL
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use*; D011379:Prognosis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*
D000975:Antioxidants; D016207:Cytokines; D011341:Probucol; D009638:Norepinephrine