We recently reported that chronic unpredictable stress (CUS) induced left ventricular dysfunction (LVD) in rats, which was inhibited by the cardioprotective agent quercetin. Based on these findings and because majority of patients with myocardial infarction (MI) can develop LVD and heart failure, we sought to produce an animal model of MI and LVD in rats and use this model to test the hypothesis that quercetin is able to prevent the potential MI induction by CUS. Rats were exposed to CUS using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day) for 21 days. Blood pressure and electrocardiogram (ECG) were recorded in all rat groups together with the examination of left ventricle (LV) tissue homogenates and sections to confirm the production of the animal model. We further extend on our recent findings on the role of apoptosis in the pathology of LVD and eventually MI. Blood pressure measurements and ECG recording confirmed the development of systemic hypertension and MI in the model group of rats exposed to CUS. In addition, histological staining confirmed that LV damages occurred in the same group. Furthermore, the proapoptotic gene Bax and the inflammatory biomarkers, TNF-α and IL-6 were augmented in LV homogenates by CUS. Simultaneous quercetin treatment lowered blood pressure and substantially prevented MI since it blocked the elevation of ST segment on the ECG and maintained a normal ECG reading. Quercetin suppressed the expression of Bax RNA messages, and significantly (p<0.05) blocked CUS-induced TNF-α and IL-6 upregulation. Thus, CUS induced MI in rats associated with augmentation of tissue injury biomarkers were prevented by quercetin, which further endorses our recent findings of a potential therapeutic role for quercetin in CUS induced cardiac dysfunction.
KEY WORDS: Chronic stress; Myocardial infarction; ECG; Rat model; Quercetin; Inflammatory biomarkers.
