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Effects of ivabradine on myocardial ischemia and reperfusion injury in rats

Grant number: 17/02537-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2017
Effective date (End): August 31, 2018
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Rubens Fazan Junior
Grantee:Camilla Rizzo Nappi
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/20549-7 - New insights in cardiovascular regulation under physiological and pathophysiological condition, AP.TEM

Abstract

Restoration of coronary flow is one of the main therapeutic tool to minimize the damage caused by acute myocardial infarction, however, it may have deleterious effects on the heart, a phenomenon known as myocardial ischemia/reperfusion injury (RI). The study of the mechanisms involved in IR injury and the knowledge of therapeutic strategies to protect the heart from IR damage are an important field of investigation. The aim of the present study is to evaluate the influence of ivabradine (IVA), a substance that induce bradycardia, in rats submitted to myocardial ischemia followed by reperfusion. Wistar rats will be implanted with subcutaneous electrodes to record the electrocardiogram (ECG) and a catheter into jugular. At the following day, the animals will have the anterior descending branch of the left coronary artery surgically ligated during 40 min, followed by reperfusion. At 10 min of myocardial ischemia the rats will receive IVA (10 mg/kg, or vehicle, iv) and the ECG will be recorded during 60 min, 2 h after cardiac reperfusion. Series of successive RR interval values (iRR) will be generated and used for analysis of heart rate variability (HRV). Mean and standard deviation as well as spectra (FFT) of stationary segments of iRR will be calculated. Nonlinear dynamics of the HRV will be studied by symbolic and detrended fluctuation analysis (DFA) and sample multiscale entropy (scales 1 to 20) will be calculated. 24 h after of ECG recording, echocardiographic examination of the rats will be performed to obtain morphological and functional indices of the heart, such as chamber diameter and cardiac wall thickness, as well as ejection and shortening fractions. After echo, a catheter equipped with a pressure transducer will be inserted into the left ventricle, via right carotid, to measure ventricular pressure of the rats. The velocity of elevation and fall of LV pressure (maximum values of positive and negative dP/dt) as well as the final LV diastolic pressure will be considered as indices of cardiac function. Finally, animals will be killed with anesthetic overdose and hearts will be collected for histopathological analysis (collagen quantification and ventricular myocyte morphometry). (AU)