Rat Models of Ventricular Fibrillation Following Acute Myocardial Infarction

Abstract

A number of animal models have been designed in order to unravel the underlying mechanisms of acute ischemia-induced arrhythmias and to test compounds and interventions for antiarrhythmic therapy. This is important as acute myocardial infarction (AMI) continues to be the major cause of sudden cardiac death, and we are yet to discover safe and effective treatments of the lethal arrhythmias occurring in the acute setting. Animal models therefore continue to be relevant for our understanding and treatment of acute ischemic arrhythmias. This review discusses the applicability of the rat as a model for ventricular arrhythmias occurring during the acute phase of AMI. It provides a description of models developed, advantages and disadvantages of rats, as well as an overview of the most important interventions investigated and the relevance for human pathophysiology.

Role of induced pluripotent stem cells in diagnostic cardiology

“…Prolonged repolarization leads to the occurrence of early after depolarization (EAD) currents. EADs are dangerous because they favor the occurrence of triggered activity (defined as the occurrence of spontaneous action potentials occurring during phase 2 or phase 3 of repolarization, leading to the production of inappropriate action potentials and arrhythmia)[ 12 ]. Blockade of the IKr also causes the QT interval to be prolonged, leading to the triggered activity via a slightly different mechanism[ 22 ].…”

“…The occurrence of any specific conduction abnormality - including QT prolongation, altered action potential duration, triggered activity, the blockade of human-ether-a-go-go-related channel (hERG) and other ion conduction channels-and the occurrence of lethal arrhythmias-such as Torsades de Pointes (TdP)-cannot reliably be predicted with currently available screening methods (Langendorf preparations, patch-clamp, or even arterially perfused isolated rabbit left ventricular wedge)[ 11 ]. Animal models are problematic predictors of arrhythmia occurrence because of anatomic variations[ 12 - 16 ]. Such an issue poses a huge difficulty for drug makers trying to produce effective antiarrhythmic drugs; animal-to-human extrapolation is an uncertain process, which can pose a danger to patients if unrecognized differences emerge between animal and human models[ 17 ].…”

Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits

“…The acute phase of myocardial infarction is characterized by great instability that results in episodes of VF and sudden death in patients. Factors, such as the extent of the ischemic area, the characteristics of collateral flow, the speed of the establishment of the coronary irrigation deficit, the activity of the autonomic nervous system, and the presence of the reperfusion phenomenon, play a role [8,18]. In chronic models of myocardial damage due to ischemia/reperfusion, there are other factors, including the structural alterations inherent to the healing process, that determine the characteristics of the substrate that facilitates the appearance of certain arrhythmias, such as VT and/or VF.…”

“…The use of animal models to study ischemic heart disease and, more specifically, the phenomena that characterize the processes of myocardial ischemia and reperfusion has provided a wide range of information. This information covers the molecular mechanisms and signaling pathways involved in the development of myocardial damage to the local and general regulatory mechanisms that can be modified to protect and limit the adverse consequences of the disease, including remodeling, ventricular dysfunction, cardiac arrhythmias, and sudden death [ 7 , 8 , 10 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Sudden cardiac death is a major public health problem.…”

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf‐2/HO‐1 pathway

“…The presence of significant and sustained ischemia causes subsequent cardiomyocyte necrosis. [2,3] Further, reperfusion can cause heart failure and ventricular remodeling during reoxygenation. This activates the cardiac compensatory mechanism through sympathetic tone, which increases the secretion of catecholamines leading to myocardial injury.…”