Role of Ivabradine in Vivo Myocardial Ischemia and Reperfusion Injuries Induced in Rats
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- Category: Vol. 79, March 2011
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Role of Ivabradine in Vivo Myocardial Ischemia and Reperfusion Injuries Induced in Rats,AMANI N. SHAFIK, HISHAM A. AWAD, AHMED SOLIMAN and MARY E. ATTIA
Abstract
Background and Aim: Higher heart rate may induce or exacerbate myocardial ischemia that is why rate-slowing drugs are considered to be the cornerstone of anti-ischemic therapy. Ivabradine is the representative of a novel class of drugs that exclusively reduce heart rate through selective inhibition of If current.
The present study aiming to investigate the effects of ivabradine on the Ischemia and Reperfusion-induced cardiac infarction in an in vivo rat model and to compare its protective effect to that of propranolol. As well as the possible mecha-nisms of infarction reduction by ivabradine were studied.
Animals and Methods: The study was carried out on male albino rats for in vivo study and rabbits for in vitro study. To produce cardiac damage, the left anterior descending coronary artery (LAD) was occluded for 90min followed by 120min reperfusion in a urethane 25% anesthetized rats. Ivabradine and propranolol were given prophylactically orally daily for 15 days before ligation of the LAD and ivabradine therapeu-tically was injected intraperitoneal during ischemia 15min after ligation and 5 minutes before reperfusion of the LAD. The changes in the ECG as regard the heart rates (bpm) and ST segment (mv) levels and their percentage reduction (in relation to controls) were recorded. Also the hearts were biopsied, stained with Hematoxylin-Eosin stain and examined under the light microscope.
The effects of gradually increasing doses of ivabradine on the inotropic and chronotropic properties of the heart were recorded from an isolated perfused rabbit heart as well as dose response for phenylephrine was recorded and the effect of cumulative doses of ivabradine on top of the submaximal dose of phenylephrine were measured and recorded on a power Lab from isolated rabbits aorta.
Results: The heart rate, ST segment level and the infarction size were significantly reduced in the ivabradine and propra-nolol prophylactic groups. The decrease in heart rate was more with ivabradine than with propranolol prophylaxis. Also in the ivabradine treated either given after ligation of the LAD or before reperfusion, all parameters were progressively reduced. Ivabradine in cumulative doses produced relaxant effect on phenylephrine induced rabbit aortic contraction.
Conclusion: Both ivabradine and propranolol showed equal protection against ischemic injury. Long term prophylaxis by ivabradine is more effective than ivabradine treatment against ischemic injury. Ivabradine attenuated the reperfusion injury. Cumulative doses of ivabradine showed antispasmogen-ic effect on isolated rabbit aorta.