Abstract
Myocardial infarction (MI) continues to be a major public health problem in the world. The present study aimed to elucidate the protective effect of different doses of rosuvastatin and cilostazol, as well as their combination on isoprenaline-induced MI in rats as well as their effects on isolated aorta. Methods: I- Adult rats received different doses of rosuvastatin (1,2,5,10, & 20mg/kg), cilostazol (18mg/kg) and combination of rosuvastatin 1mg/kg and cilostazol 18mg/kg by oral gavage daily for 16 days, then rats were subcutaneously injected with two doses 24-h apart of 150mg/kg isoprenaline in the last two days. ECG pattern was monitored, myocardial injury markers (CK-MB and LDH) and inflammatory biomarker (CRP) were measured in serum. MDA, catalase and SOD were quantified in cardiac homogenates and heart tissue damage was examined by histopathology. II- Effects of rosuvastatin (0.2 µg/ml – 6.4 µg/ml), cilostazol (7.5 µg/ml – 480 µg/ml) and combination cilostazol (30 µg/ml) and rosuvastatin (0.2 µg/ml – 6.4 µg/ml) on NE-induced contraction in rabbit aortic strip were recorded. Each dose of either rosuvastatin or cilostazol were incubated for 10 min and 15min respectively then NE (0.5 µg/ml) was added and the contraction was recorded for one and half min. Results: I- Pretreatment with different doses of rosuvastatin (1,2,5 & 10), cilostazol 18mg/kg and the combination markedly ameliorated ISO-induced alterations in ECG, cardiac markers, inflammatory marker, oxidative markers and heart architecture. However, protection disappeared at higher dose of rosuvastatin 20mg/kg. II- Addition of either rosuvastatin (0.2-6.4 µg/ml), cilostazol (7.5-480µg/ml) or combination rosuvastatin (0.2-6.4 µg/ml) and cilostazol 30µg/ml produced a significant decrease in the height of NE-induced contraction in a dose dependent manner. Conclusion: I-This study provides evidence that rosuvastatin, cilostazol and their combination possess cardioprotective effect on isoprenaline-induced myocardial infarction. II- The drugs had vasorelaxant effect on aorta. Mechanism of drug action are discussed.
Highlights
Acute myocardial infarction (AMI) is among the most prevalent health problems in the world, and is a major cause of morbidity and mortality (Abdikarim and Basgut, 2016)
In the present study we aimed to investigate the protective effect of different doses of rosuvastatin, cilostazol and their combination in cardiac ischemia to determine the most effective dose in protection of the heart
Subcutaneous injection of isoprenaline (150mg/kg) for two successive days induced Myocardial infarction (MI) represented by significant increase of ST segment elevation and decreased in heart rate in ischemic group as compared with non ischemic group
Summary
Acute myocardial infarction (AMI) is among the most prevalent health problems in the world, and is a major cause of morbidity and mortality (Abdikarim and Basgut, 2016). Isoprenaline (ISO) induced myocardial infarction is widely used experimental model for several reasons. The model is characterized by technical simplicity, an excellent reproducibility as well as an acceptable low mortality (Dhakad et al, 2017). Subcutaneous injection of ISO causes imbalance between oxygen supply and demand by the cardiomyocytes through increasing the chronotropism and inotropism important to overt myocardial function and increase in the calcium overload in the myocardium (Lobo Filho et al, 2011). Rosuvastatin is one of the most potent inhibitors of HMG-CoA reductase enzyme. Rosuvastatin, has an appreciable anti-atherogenic property which is due to the improvement of endothelial dysfunction as well as its anti-thrombotic, antiinflammatory and antioxidant effects (Rondi et al, 2014). Statins are among the drugs which can protect against myocardial ischemia-reperfusion injury (Balakumar and Mahadevan, 2012)
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