Left Ventricle Radio-frequency Ablation in the Rat: A New Model of Heart Failure due to Myocardial Infarction Homogeneous in Size and Low in Mortality EDNEI L. ANTONIO, 1 ALEXANDRA A. DOS SANTOS, 2 SE ´ RGIO R.R. ARAUJO, 3 DANILO S. BOCALINI, 1 LEONARDO DOS SANTOS, 2 GUILHERME FENELON, 2 MARCELO F. FRANCO, 3 AND PAULO J.F. TUCCI 1 Sa ˜o Paulo, Brazil ABSTRACT Background: The purpose of the current study was to create a model of myocardial infarction (MI) that is homogeneous in size with a low immediate (24 hours) mortality. Methods and Results: Male and female rats (n 5 256) underwent left ventricle (LV) ablation (Ab) by a radiofrequency current (1000 kHz; 12 watts for 12 seconds) to promote a MI. A transmural MI occurred in all rats. Post-Ab complex arrhythmias were frequent (atrioventricular block, ventricular tachycardia, and fibrillation), which rapidly and spontaneously reverted to sinus rhythm. Among 66 male rats, imme- diate mortality occurred in 7.5%. Small MI size dispersion was characterized by smaller variability fol- lowing Ab (x 6 SD: 45 6 8%) when compared with coronary occlusion (Oc; 40 6 19%). The histopathologic evaluations identified lesions similar to those which occurred following Oc, with scarring complete at 4 weeks. The hemodynamic and Doppler echocardiograms showed comparable increases in LV dimension, end-diastolic pressure, and pulmonary water content 1 and 4 weeks post-MI. Papillary muscle mechanics 6 weeks post-MI had matched inotropic and lusitropic dysfunction. Conclusions: LVAb gave rise to a MI within a narrow size limit and with a low immediate mortality. LV Ab resulted in histopathologic evolution, ventricular dilation, and dysfunction, impairment in myocardial mechanics, and congestive outcome that reproduced a MI from Oc. (J Cardiac Fail 2009;15:540e548) Key Words: Rats, myocardial infarction, radiofrequency ablation, heart failure. Myocardial infarction (MI) in rodents is by far the most frequently used animal model to experimentally reproduce human congestive heart failure (CHF), with left coronary surgical occlusion being the traditional method used to achieve an MI. This model has been validated to simulate human CHF, as evidenced by the large number of publica- tions and has provided relevant information on this matter. There is, however, general agreement regarding 2 draw- backs to this rat model: high immediate mortality rate after coronary occlusion (Oc) 1e5 and high variability in the resulting size of the MI (MIS), despite well-established pat- terns for Oc. 5,6 Cryoinjury has been proposed as an alterna- tive method for generating an MI in an effort to eliminate such drawbacks. 7e10 Since cryoinjury was first described, good results have been reported by some authors, 7,8 whereas others have achieved results that are not as satis- factory. 9,10 Myocardial ablation (Ab) with radiofrequency currents (RF) is a method routinely used in clinical practice for the treatment of cardiac arrhythmias. The main cause of tis- sue injury by RF ablation is thermally mediated, producing a discrete homogeneous lesion characterized by typical coagulation necrosis, which is completely replaced by fibrosis. 11e14 The mechanism by which RF current heats tissue involves resistive heating of a narrow rim of tissue that is in direct contact with the ablation electrode. Deeper tissue heating occurs as a result of passive heat conduction from this small region of volume heating. The small num- ber of arrhythmias triggered by RF Ab, as well as the pos- sibility of controlling the size of the myocardial lesion, has generated interest in the technique. Such characteristics of From the 1 Departments of Physiology, Cardiovascular Division; 2 Med- icine, Cardiology Division; and 3 Pathology, Federal University of Sa ˜o Paulo (UNIFESP), Brazil. Manuscript received May 30, 2008; revised manuscript received January 21, 2009; revised manuscript accepted January 21, 2009. Reprint requests: Paulo J. F. Tucci, MD, PhD, R. Estado de Israel 181/94 CEP: 04022-000, Sa ˜o Paulo, Brazil. Tel-Fax: (5511) 5573-7820; E-mail: paulotucci@terra.com.br Supported by Fundac ¸a ˜o de Amparo a ` Pesquisa do Estado de Sa ˜o Paulo, Ministe ´rio da Cie ˆncia e Tecnologia (CNPq), Universidade Federal de Sa ˜o Paulo. 1071-9164/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.cardfail.2009.01.007 540 Journal of Cardiac Failure Vol. 15 No. 6 2009