Table 1.
Schematic comparison of the different animal models used in cardiovascular imaging research.
| Specie | Model | Failure etiology | Advantages | Disadvantages |
|---|---|---|---|---|
| CARDIAC HYPERTROPHY | ||||
| Mouse | Transverse aortic and pulmonary artery constriction | Acute and pressure overload | Easy use of GEM animals. Hypertrophy developed rapidly (2–3 weeks) | Surgical skills. Acute hypertension and expense of equipment for cardiovascular imaging and physiology assessment |
| Mouse | Isoproterenol infusion | Toxic injury of myocardium | Minimal surgery and good scenario for pharmacological or gene therapy | Hypertrophy is adjusted to dose and mouse strain |
| Rat | Spontaneous hypertensive rat and Dahl salt-sensitive rat | Chronic pressure overload | The onset of hypertension is gradual, being the heart failure in later stages. Genetic origin of hypertension. No surgery | Long experimental period (6–12 months) |
| Rat | Ascending aortic and pulmonary artery constriction | Gradual to quick onset pressure overload | Gradual to quick onset hypertension | Less GEM animals and similar cost of equipment for cardiovascular physiology assessment than mouse |
| Rat | Arteriovenous shunts | Overload of ventricular chambers | Progressive heart hypertrophy, more rapidly in the right ventricle. Well tolerate and it possible to reverse the volume-overload state | Greater surgical skills, with a grade of hypertrophy fistula localization-dependent |
| Guinea pig | Descending aortic constriction | Pressure overload and hypertension | Human mimicking alteration of sarcolemma calcium handling | Special and expensive requirements for husbandry |
| Rabbit | Aortic and pulmonary constriction | Gradual onset pressure overload | Imaging technology allows normalizing the grade of constriction. Possibility to reverse the pressure-overload situation | Thoracotomy surgery required |
| Rabbit | Doxorrubicin | Toxicological aggression | Myocyte function and structure modification | High risk of mortality dose dependent |
| Dog | Aortovenus shunt | Volume overload | Progressive heart hypertrophy, more rapidly in the right ventricle | Not so well tolerated than rats. Frequent arrhythmias, edema and quick health decrease |
| Dog | Arrhythmogenic right ventricular cardiomyopathy of Boxer | Desmosomes proteins mutation | Genetic origin which mimic the human disease | Social ethical considerations |
| Cat | Inherited Hypertrophic Cardiomyopathy of Maine Coon and Persian strains | Sarcomeric protein gene mutations | Genetic origin which mimic the human disease | Social ethical considerations |
| Pig | Descending aortic constriction | Pressure overload and hypertension | Progressive hypertrophy and animal well adapted (constriction grade progresses with animal growth) | Surgical skills and lateral thoracotomy |
| Pig | Pulmonary artery hypertension by microembolization | Increased vascular resistance | Progressive hypertrophy of right ventricle and final heart failure by dilated cardiomyopathy. No surgery | Great hypoxic vasoconstriction |
| Sheep | Ascending aortic constriction | Pressure overload and hypertension | Transition from compensated hypertrophy to left ventricular dysfunction | Zoonotic risk |
| Sheep | Pulmonary artery hypertension by microembolization | Increased vascular resistance | Progressive hypertrophy of right ventricle and final heart failure by dilated cardiomyopathy. No hypoxic vasoconstriction No surgery | Zoonotic risk |
| DILATED CARDIOPATHY | ||||
| Mouse | Genetic Engineering modified animals (GEM) | Dilated cardiomyopathy | Genetic modifications of structural and functionality of cardiomyocytes. No required surgery | Clinical reliability restricted to the molecule of study: e.g., TNF-α overexpression |
| Rat | Isoproterenol toxicity | Toxicological aggression | Severe structural modification by necrosis and fibrosis of myocardium | Less GEM animals and similar cost of equipment for cardiovascular physiology assessment than mouse |
| Rabbit | Pacing Tachycardia | Congestive failure by low output | Mimic myocardial alteration of human edematous chronic low output | Limited imaging technology due to paced heart rate (400 beats/min) |
| Rabbit | Balloon occlusion of circumflex branch of left coronary artery | Myocardial infarction | Artery occlusion by catheterization | Great skill and specific material |
| Dog | Pacing Tachycardia | Congestive failure by low output | Mimic myocardial remodeling, neurohumoral activation and subcellular dysfunction | No hypertrophy |
| Dog | Coronary microembolization | Contractile dysfunction and a profound perfusion-contraction mismatch | No surgery requirements | Microspheres are chemically inert. Extensive arterial pattern of heart. Time consuming |
| Pig | Pacing Tachycardia | Congestive failure by low output | Mimic myocardial remodeling, neurohumoral activation and subcellular dysfunction | No hypertrophy nor fibrosis |
| Pig | Coronary microembolization | Contractile dysfunction and a profound perfusion-contraction mismatch | No surgery requirements | Microsphere are chemically inert |
| Pig | Hibernating myocardium | Progressive reduction of ventricle perfusion | Mimic human disease condition | Surgical technical experience and skill. There is a myocardial recovery in chronic studies |
| Sheep | Pacing Tachycardia | Congestive failure by low output | Mimic myocardial remodeling, neurohumoral activation and subcellular dysfunction | No hypertrophy nor fibrosis |
| Sheep | Coronary microembolization | Contractile dysfunction and a profound perfusion-contraction mismatch | No surgery requirements and resemble human condition than dog | Zoonotic risk. Microspheres are chemically inert. Extensive arterial pattern of heart. Time consuming |
| MYOCARDIAL INFARCTION | ||||
| Mouse | Left coronary ligation (total occlusion or ischemia/reperfusion) | Myocardial infarction | Easy use of GEM animals, low cost of husbandry and feasible cardiovascular assessment. Suitability for follow-up and survival studies. | Great surgical skill and expensive technological requirements. Limited sample collection (animal size) |
| Rat | Left coronary ligation (total occlusion or ischemia/reperfusion) | Myocardial infarction | Surgical procedure easier than in mouse and more volume of samples. Lower cost than large animals. Suitability for follow-up and survival studies. | Less GEM animals and similar cost of equipment for cardiovascular physiology assessment than mouse |
| Rabbit | Left coronary ligation (total occlusion or ischemia/reperfusion) | Myocardial infarction | Surgical procedure easier than in rodents and more volume of samples Lower cost than large animals. | Thoracotomy surgery required |
| Dog | Left coronary ligation (total occlusion or ischemia/reperfusion) | Myocardial infarction | Surgical procedure easier than in rodents and more volume of samples Lower cost than large animals. | High death incidence by arrhythmias |
| Pig | Angioplasty balloon occlusion of the left anterior descending coronary | Myocardial infarction | Anatomy and pathology closed to human. Good suitability to undergo imaging techniques. No surgery requirements. | Require skills for coronary catheterization and surgical specific material |
| Zebrafish | Myocardial criolesion | Myocardial infarction | Heart remodeling and regenerative model | Far of mammals biology |
| VASCULAR DISEASE | ||||
| Mouse | APOE-deficiency and LDL Receptor deficiency | Atherosclerosis, Aortic root atherogenic lesions | Easy use of GEM animals, low cost of husbandry and feasible cardiovascular assessment. Great valuable data of molecular and cellular events. | Not mimic exactly the human chronic disease. The artery low size complicates the in vivo imaging acquisition |
| Rabbit | High-fat diet with/without balloon aortic injury | Atherosclerosis, Aortic arch and thoracic aorta lesions | Easy husbandry and feasible artery imaging acquisition. | Great skill for vessel damage, long term experimental induction of atherogenic lesions and no coronary affection |
| Rabbit | Watanabe WHHL (LDL Receptor deficiency) | Atherosclerosis, Aortic arch and thoracic aorta lesions | Easy husbandry and feasible artery imaging acquisition. Possible finding of coronary artery lesions. Not necessary high fat diet. | Unstable atherogenic plaque which could develop coronary occlusion and death |
| Pig | High-fat diet with/without angioplasty | Atherosclerosis, Aortic and coronary atherogenic lesions | Model closed to human disease | Long term experimental induction of atherogenic lesions. Skills for catheterism |
| PULMONARY HYPERTENSION | ||||
| Rat | Chronic Hypoxia | Increase in vascular tone | Repeatable maintained increase in pulmonary artery and RV pressure accompanied by RV remodeling | Minimal vascular remodeling. Suitable just for small animals |
| Rat | Chronic Hypoxia plus SU5416 | Increase in vascular tone plus VEGFR-R blockade | Equal than chronic hypoxia more angiobliterative changes. More increase in RV pressure and more RV hypertrophy | Suitable just for small animals |
| Rat, dog, pig, sheep | Monocrotaline | Endothelial damage | Produces RV failure and vascular remodeling | No plexogenic arteriopathy |
| Dogs pig, sheep | Beads or clots injection | Decrease in total vessel area | Acute increase in pulmonary pressure RV remodeling | Decrease of the severity of vascular and RV changes with time. Hard to titrate the dose. High mortality in some reports |
| Pig, Rat | Aortocaval shunt | Increase in pulmonary artery flow | Resembles major features of human disease | Requires surgical skills. Complications related with surgery |
| Rodents, pig, sheep, dog | Vascular banding | Decrease in vascular compliance | Controllable and maintained increase in pulmonary artery pressure. RV remodeling | Requires surgical skills. Complications related with surgery |