Increased heart rate (HR) is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease.
Increased resting heart rate has emerged as an independent risk factor in patients with hypertension, coronary artery disease, atherosclerosis and myocardial infarction. A reduction in increased resting heart rate has long been postulated as a therapeutic approach in the management of cardiovascular disease.
Ivabradine is a selective inhibitor of the sinus node If current reducing resting and exercise heart rate without affecting cardiac contractility. Carvedilol is non selective beta blocker with α1-blocking activity decreasing heart rate, decreasing contractility, vasodilator and has antioxidant effect. Heart rate reduction by both drugs through different mechanisms plays a role in the medical treatment of myocardial ischemia.
The present work was carried out to screen the cardioprotective effect of ivabradine and carvedilol on experimentally-induced hypertension, myocardial infarction and adrenaline-induced arrhythmia. In addition, the present work studied the effect of ivabradine on isolated rabbit's aortic spiral strip and isolated rabbit's heart.
In the current work, experimentally induced hypertension by chronic administration of L- nitro arginine methyl ester (L-NAME) to rats by gavage in a daily dose (20 mg/kg) for a period of 4 weeks produced significant increase in mean blood pressure (MBP).
In the present study, treatment with both ivabradine (10mg/kg/day) and carvedilol (30mg/kg/day) by gavage for 4 weeks elicited significant decrease in MBP. Carvedilol was more significantly reduce it than ivabradine.
Myocardial infarction was experimentally induced by a single subcutaneous injection of isoprenaline (150mg/kg). The electrocardiograph tracing showed sinus tachycardia with injury currents in form of highly peaked T-wave, serum creatine kinase (CK-MB) and troponin-I levels increased in rats 4 hours after subcutaneous injection of isoprenaline. Histopathological examination of cardiac sections of MI group revealed myocyte degeneration, necrosis and interstitial fibrosis.
In the present study it was observed that both ivabradine (10mg/kg/day) and carvedilol (30mg/kg/day) administration by gavage for 4 weeks produced significant decrease in T-wave voltage as well as heart rate with insignificant difference between them.
The preseant study show that in both ivabradine and carvedilol groups of rats, the serum CK-MB and troponin-I levels 4 hours after isoprenaline injection was significantly decreased compared to MI group with insignificant difference between them.
Histopathological study indicated that in ivabradine and carvedilol groups there are little signs of acute infarction (in form of slight atrophic cardiomyocytes) compared to MI group.
In the current work, the protective effects of ivabradine (10mg/kg) and carvedilol (1mg/kg) in adrenaline-induced arrhythmia in anaesthetized rats were investigated. The results revealed that both ivabradine and carvedilol had a prophylactic effect against adrenaline-induced arrythmias.
Data obtained in the present study pointed out that ivabradine in gradually increasing doses (2,4,8,16 and 32/ml bath) produce no effect on the isolated rabbit’s aortic strip and basal myocardial contractility of isolated rabbit’s heart.
From the results of present study, treatment with ivabradine has significant effect against L-NAME induced hypertension, while carvedilol has more significant effect.
On the other hand both ivabradine and carvedilol have cardioprotective effect against acute MI as well as adrenaline-induced arrhythmia with no significant difference between both drugs, also ivabradine has no effect on contractility of the heart.. So, the choice of either drug in these disease states depend on which of them has low side effects.
Recommendations
The present experimental study supports the concept that increased heart rate is deleterious to the cardiovascular system. The results of the present work provide impetus for testing the impact of ivabradine in association of classic medication in treatment of myocardial infarction and arrhythmia. Further studies are needed to know the exact role of ivabradine in hypertension and illustrate the role of ivabradine to restore endothelial dysfunction.
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