Table 1 Animal models of arrhythmia disorders.
From: New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models
Animal | Notes/limitations | |
|---|---|---|
In vitro models | ||
Pig | Studies on isolated ventricular Myocytes: Can be induced minimally invasively with low mortality, model of TdP | |
Pig, Dog | Isolated guinea pig papillary muscles: Limitation to ventricular arrhythmia | |
Pig | Patch-Clamp Experiments in CHO Cells: Limitation to atrial Fibrillation | |
Pig | Isolation of Porcine Atrial Myocytes: Limitation to atrial Fibrillation | |
Pig | Isolation of guinea pig ventricular myocytes: Limitation to ventricular arrhythmia | |
Pig, Rat | Isolated guinea pig papillary muscle: action potential and refractory period: Limitation to ventricular arrhythmia | |
Rat, Pig, Dog, Rabbit | Langendorff technique: vulnerability to atrial and ventricular Fibrillation | |
Rabbit | Acetylcholine or potassium-induced arrhythmia: vulnerability to atrial and ventricular Fibrillation | |
Animal models of aquired arrhythmia disorders | ||
Transverse aortic constriction | ||
Mouse | Severity of injury dependent on strain (BALB/c > C57BL/6 > 129S1/SvImJ) and sub-strain (C57BL/6Tac > C57BL/6NCrl > C57BL/6J). Model requires PES to induce in vivo arrhythmias | |
Rat | Develop spontaneous arrhythmias with catecholamine challenge | |
Guinea Pig | High mortality, develops catecholamine-induced arrhythmias | |
Rabbit | In vivo injury, but arrhythmia studies completed ex vivo with Langendorff system | |
Pig | Model of heart failure with preserved ejection fraction, study of arrhythmias | |
Sheep | Model of heart failure with reduced ejection fraction, study of arrhythmias | |
Myocardial ischemia | ||
Mouse | Single left coronary artery leads to variation in severity of injury. Model requires PES with catecholamine challenge to induced arrhythmias | |
Rat | Requires PES and catecholamine challenge to induce ventricular arrhythmias reliably but rare spontaneous arrhythmias | |
Rabbit | PES done as ex vivo in Langendorff system | |
Dog | Atrial ischemia extensive studied | |
Pig | High mortality due to poor collateral circulation, early spontaneous VT/VF during injury and late model of SCD | |
Sheep | High mortality with spontaneous ventricular arrhythmia | |
AV node ablation | ||
Rat | High mortality, particularly in male rats. Requires specialized surgical equipment and skill | |
Rabbit | Studied completed ex vivo in Langendorff system | |
Dog | Can be induced minimally invasively with low mortality | |
Sheep | Can be induced minimally invasively with low mortality, model of TdP | |
Chronic atrial pacing | ||
Rat | Model for AF | |
Rabbit | In vivo pacing, but PES studied completed ex vivo with Langendorff system | |
Dog | AF and spontaneous VT model, recapitulates tachycardia mediated cardiomyopathy | |
Pig | AF model, recapitulates tachycardia-mediated cardiomyopathy | |
Chronic ventricular pacing | ||
Mouse | Requires tethered or ex vivo pacing | |
Rat | Model tachycardia mediated cardiomyopathy with VF induction with rapid pacing | |
Dog | Recapitulates tachycardia-mediated cardiomyopathy, model of spontaneous AF and VT | |
Sheep | Recapitulates tachycardia mediated cardiomyopathy with reduced ejection fraction, no studies of arrhythmia | |
Pig | ||
Inflammation | ||
Mouse | Strain-specific susceptibility. C3H/He and DBA/2 mice susceptible to viral myocarditits while C57BL/6 are protected. BALB/c susceptible to immunogen induced myocarditis while C57BL/6 more resistive | |
Rat | Model of AF, but nonphysiological induction of inflammation with talc | |
Guinea Pig | ||
Dog | ||
Sheep | ||
Metabolic/drug-induced | ||
Mouse | Streptozotocin and DIO models well established, increased susceptibility to AF and VT with PES | |
Rat | Age-dependent fibrosis found in Fisher 344 rat strain, model of AF | |
Rabbit | Established model of clofilium-induced TdP | |
In vivo approaches | ||
Arrhythmia of chemical origin | ||
Male Ivanovas rats | Rats with Aconitine Antagonism: With regard to ventricular extrasystoles, tachycardia, fibrillation, and death, the antiarrhythmic action of the test substance is quantified | |
Guinea Pig | Arrhythmias in Whole Guinea Pigs Caused by Aconitine: induce ventricular arrhythmias in a whole animal model | |
Male Marioth guinea pigs | Digioxin developed arrhythmia in guinea pigs: ventricular premature beats, fibrillation, and cardiac arrest | |
Rats, Rabbits | Strophanthin/Ouabain-induced Arrhythmia: ventricular premature beats, fibrillation, and cardiac arrest | |
Dogs | Adrenaline-induced Arrhythmia: induce ventricular arrhythmias in a whole animal model | |
Rats | Calcium-induced arrhythmia: ventricular flutter and fibrillation | |
Electrically triggered Arrhythmia | ||
Dogs | Ventricular Fibrillation Electrical Threshold: Atria & ventricular thresholds were assessed using a variety of electrical pacing techniques, including sequential pulse pacing | |
Dogs | Programmed Electrical stimulation induced Arrhythmia: sustained ventricular tachycardia and ventricular fibrillation | |
Male mongrel dogs | Dog Model of Sudden Coronary Death: Coronary artery stenosis investigations into the onset of lethal arrhythmia and ventricular ectopy are conducted using recordings from the cardiocassette evaluation of tachyarrhythmias | |
Rats, Dogs | Exercise-related ventricular fibrillation: Coronary artery stenosis of exercise on the treadmill | |
Mechanically generated arrhythmia | ||
Rats | Reperfusion Arrhythmia in Rats: Ventricular arrhythmia and myocardial infarction by ligation of the left major coronary artery in the course of the ligation and subsequent reperfusion | |
Dogs | Reperfusion Arrhythmia in Dogs: Ventricular arrhythmia and myocardial infarction by ligation of the left major coronary artery in the course of the ligation and subsequent reperfusion | |
Mice, Rats, Dogs, Guinea Pigs, Rabbits, Monkeys | Genetically Prone Arrhythmias. Limitations: Limited to embrogenic gene manupulations, ie. Gene mutations and gene knockout varients | |
Mice, Rats, Dogs, Guinea Pigs, Rabbits, Monkeys & Humans Stem cell cardiomyocytes | Arrhythmia Mechanisms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes; Limitations: When compared with native human ventricular tissue, hiPSC-based EHTs lack a positive force–frequency relation, which is one of the hallmarks of cardiac contractility. Furthermore, the frequency-dependent acceleration of relaxation is much weaker in EHTs | |
