P444Therapeutic and prophylactic effects of oleuropein on ischemic and reperfusion injury of the heart in an in vivo and in vitro rat model

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Purpose: Oleuropein is a very powerful phenolic antioxidant that exists in high concentrations in olive leaves. Several pharmacological benefits have been reported about oleuropein that nearly all of them linked to its antioxidant property. Given that oxidants play an important role in the incidence of ischemic cardiovascular diseases, in this study we wanted to evaluate the direct effects of oleuropein on the myocardial performance and incidence of arrhythmia in isolated and anesthetized rat heart models.

Methods: One hundred and twenty male Wistar rats were used to perform this study. To evaluate the direct effects of 10 and 100 μg/kg of oleuropein (perfusion of heart with solution containing oleuropein) on myocardial performance as a therapeutic and prophylaxis in isolated heart model, fifty rats were divided into five groups of eight in each. Also, to evaluate the direct effects of intravenous oleuropein (10 and 50 mg/kg in 1 ml normal saline) on the hemodynamic parameters and incidence of arrhythmia as a prophylaxis and therapeutic manner, fifty rats were divided into five groups of ten in each.Twenty male Wistar rats were divided into two groups of ten to evaluate the direct effects of lidocaine on the incidence of reperfusion arrhythmia in anesthetized rat as the positive control groups.

Results: The results showed that in isolated rat hearts, oleuropein in the manner of prophylaxis and therapeutic significantly decreased ischemia - reperfusion injuries that was evident with reduction of left ventricular end diastolic pressure and augmentation of contractility, coronary flow and ±dp/dt. In anesthetized rat hearts, intravenous administration of 10 mg/kg oleuropein had not significant effects on the mean arterial pressure and heart rate, but administration of 50 mg/kg oleuropein reduced the mean arterial pressure significantly without any effect on heart rate. Oleuropein in the manner of prophylaxis and therapeutic had a mild effect on the magnitude of reperfusion arrhythmia in anesthetized rat heart that was evident with increasing onset time of arrhythmias and reduction in the incidence of irreversible ventricular fibrillation. Antiarrhythmic effects of oleuropein were much weaker than the effects of lidocaine as an standard antiarrhythmic drug that was commonly used to treat the ventricular arrhythmia in clinic.

Conclusions: the results of this study shown that oleuropein has direct cardiotonic, vasodilator, anti-arrhythmic and hypotensive effects. Antiarrhythmic effect of oleuropein was much weaker than lidocaine as a standard antiarrhythmic drug in clinic.

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