الفهرس 
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Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Deaths are mostly attributable to coronary artery diseases (CAD). Ivabradine, a pure heart rate lowering agent, acts by inhibiting the pacemaker If current in the sinoatrial node. It can be used in combination with the main drugs for CVD in heart failure and stable angina.
This study aims to determine the effect of ivabradine pretreatment alone and in combination with each of atenolol and enalapril on acute myocardial infarction (MI) in rats.
Eighty four rats were divided into seven groups (12 rats each): group 1: sham-operated group; group 2: control (untreated) MI; group 3: ivabradine-pretreated; group 4: atenolol-pretreated; group 5: enalapril-pretreated; group 6: ivabradine+atenolol-pretreated; and group 7: ivabradine+enalapril-pretreated. Rats received drugs orally by gavage once daily for 6 days. On the sixth day, acute MI was induced by persistent complete left coronary artery ligation. The parameters studied were mean arterial blood pressure, ECG changes (heart rate, ST height and T-wave voltage), serum levels of creatine kinase MB isoenzyme (CK-MB), cardiac troponin-I (cTnI), high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain-type natriuretic peptide (NT-proBNP), tissue levels of superoxide dismutase (SOD), reduced glutathione (GSH), Bcl-2-associated X protein (Bax) and the % of infarction size of the left ventricle.
Coronary artery ligation resulted in significant elevation in ST height, T-wave voltage, serum levels of CK-MB, cTnI, hs-CRP, and NT-proBNP, and tissue levels of Bax, with significant reduction of the tissue levels of SOD & GSH and produced 54% infarct size of the left ventricle. Oral pretreatment with ivabradine has cardioprotective effect against acute MI as evidenced by significantly lower ST height, T-wave voltage, the serum levels of CK-MB, cTnI, hs-CRP, NT-proBNP, and tissue levels of Bax, with significantly higher tissue levels of SOD & GSH, and significantly lower infarct size into 39%. Oral pretreatment with combination of ivabradine and atenolol produced greater cardioprotection against acute MI than observed with ivabradine alone evidenced by significantly lower ST height, T-wave voltage, serum levels of CK-MB, cTnI, hs-CRP, and NT-proBNP, tissue level of Bax, with significantly higher tissue levels of SOD & GSH, and significantly lower infarct size into 23%. Although, the effects of oral pretreatment with combination of ivabradine and enalapril on ST height, T-wave voltage, tissue levels of SOD & GSH, and infarct size were not significantly different from that of ivabradine; however, this combination caused significant reduction of serum levels of CK-MB, cTnI, hs-CRP, and NT-proBNP, and tissue level of Bax as compared to the effect of ivabradine alone.
It can be concluded that the use of ivabradine either alone or in combination with either atenolol or enalapril produced cardioprotective effect against acute MI and this effect is the greatest when ivabradine is combined with atenolol.