Major causes of HF Model Heart Failure Stimulus Pathology feature Limitation Species Selected references
Ischemia
Myocardial infarct
Permanent left coronary artery occlusion
LVEDD ↑, LVESD ↑, FS ↓, LV systolic pressure ↓, dP/dtmax ↓, dP/dtmin ↑
1. Model does not reflect the clinical setting with reperfusion of the occluded vessel during coronary angiography performed after an acute MI. 2. Expense of equipment for cardiovascular physiology assessment.
Mouse
(Gao et al., 2000)
LV systolic function ↓, LVEDV ↑, PRA ↑, arginine vasopressin ↑, atrial natriuretic factor ↑ Rat (Francis, Weiss, Wei, Johnson, & Felder, 2001)
Permanent coronary occlusion in the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) by acute ligation, or thrombogenic coil, hydraulic occluder and ameroid constrictor placement.
LVEF ↓, MAP ↓, LVSP ↓, LVEDP ↑
Dog
(Schneider et al., 1985) (Ferrarini et al., 2006)
LVEF ↓, LV volumes ↑, BNP, NT-proBNP and cGMP ↑ Sheep (Charles, Elliott, Nicholls, Rademaker, & Richards, 2003)
LV weight ↑, LV end-diastolic area ↑, EF ↓, Endogenous protein kinase A ↓, SERCA2a↓, TnI ↓, Ca2+ sensitivity of force (pCa50) ↑ Pig (Van der Velden et al., 2004)
Ischemia-reperfusion LAD occlusion for 30-60 min followed by reperfusion allowing flow through the previously occluded coronary artery bed. LVIDd↑, LVIDs ↓, EF ↓, FS ↓, HR ↓, LVESP ↓, LVESV↑, LVEDV ↑, SV ↓, CO ↓, +dP/dtmax ↓, −dP/dtmin ↑, SBP ↓, HW ↑, HW/BW ↑ 1. Surgery is time consuming and complex than placement of permanent LAD ligation Mouse (Reitz et al., 2019)
LVSP↓, LVEDP ↑, +dP/dtmax ↓, −dP/dtmax ↓ Rat (Y. Zhang et al., 2011)
LAD or LCx occlusion/reperfusion by PTCA balloon
LV end-diastolic pressure ↑, LV end-systolic elastance ↓, NT-proBNP level ↑
Dog
(Saku et al., 2018)
Creatine kinase ↑, Troponin-T ↑, EF ↓, FS ↓ Sheep (CHARLES et al., 2000)
EF ↓, LV +dp/dt ↓, LVEDD ↑, LV hypertrophy HW/BW ↑ Pig (Pleger et al., 2011)
Coronary microembolization
Repeated injecting glass or polystyrene microspheres into the LAD or LCx coronary artery
LVEDP ↑, EF ↓, LVEDP ↑, Cardiac output ↓, peak LV +dP/dt ↑, peak LV -dP/dt ↑, pulmonary artery wedge pressure ↑, systemic vascular resistance ↑, Plasma norepinephrine ↑, Plasma levels of atria1 natriuretic factor ↑
1. This approach requires an intracoronary injection technique, which is usually performed under the anesthesia of a special catheter inserted into a specific area or implanted into a coronary artery for a long time. 2. It is difficult to find a consistent protocol for the number of injections and the amount of microembolization. 3. this model is not easy to be repeated by most laboratories.
Dog
(Franciosa et al., 1980) (Sabbah et al., 1991)
EF↓, end-systolic elastance ↑, LVEDV ↑, myocyte nuclear density ↑, myocyte diameter ↑, LVESV ↑
Sheep
(Huang et al., 1997) (Ikeda et al., 2001)
EF↓, Body weight ↑;EDV ↑, ESV ↑, SV ↑, Left atrium ↑, dP/dtmin
Pig
(Carlsson, Wilson, Martin, & Saeed, 2009) (Ishikawa et al., 2014)
Hypertension Transgenic lines Spontaneously hypertensive rat myocardial fibrosis ↑; passive stiffness↑, LV collagen concentration↑, contractile function↓ 1. Limitations of small animal species in terms of comprehensive physiological measurement Rat (Conrad et al., 1995)
Spontaneously hypertensive HF rat RWT ↓, LVEDV ↑, LVESV ↑, LVAd ↑, LVAs ↑, EF ↓, FS ↓, E-vel ↑, A-vel ↓, IR ↓, LVLd ↑, LVM ↑, LVIDd ↑, LVIDs ↑, SV ↑ Rat (Heyen et al., 2002)
Dahl-salt-sensitive rat SWT ↑, LVEDP ↑, LVESD ↑, EF ↓, FS ↓, ESV ↓, Tau↑ Rat (Klotz et al., 2006)
Renal artery stenosis Goldblatt Hypertension method, including Two-kidney, one clip [2K1C] and one-kidney, one clip [1K1C] hypertension Systolic blood pressure ↑, HW/BW ↑, LVDd ↓, LVPWd ↑, LVM ↑, LVM/BW ↑, Ea/Aa, E/Ea ↑, dp/dtmin ↑, Tau ↑ 1. Unspecific side effects on organ systems, especially kidney. Rat (Junhong et al., 2008)
Page model, which can be produced by wrapping one or both kidneys in cellophane SBP ↑, DBP ↑, MAP ↑, arterial BPs↑, PP ↑, LVM/BW ↑, Fibrosis ↑, Tau ↑, End-systolic LV stiffness↑ Dog (Munagala et al., 2005)
DCM
Chemical induced
Intracoronary adriamycin or isoprenaline
AWT ↑, PWT ↑, LVEDD ↑, LVESD ↑, LVM/BW ↑, FS ↓, PAV ↓, VCDc ↓, SBP ↓, MABP ↓, LVEDP ↑, +dP/dtmax ↓, -dP/dtmin ↑
1. Variability of response to chemicals, the degree of LV dysfunction 2. animal mortality caused by arrhythmia, and engenders several systemic side effects, such as bone marrow suppression, gastrointestinal discomfort.
Mouse
(Oudit et al., 2003)
LVEDP ↑, volume indexes ↑, global diastolic wall stress ↑ Rat (Teerlink, Pfeffer, & Pfeffer, 1994)
EF ↓, LVEED ↑, LVESD ↑, LVESV ↑, E septal point ↑, Aprtic velocity ↓, IVRT ↑ Dog (Monnet & Orton, 1999)
SF, LVEDD ↑, LVESD ↑, SEV ↓, SMVG ↓, systolic epicardial velocity ↓ sheep (Borenstein et al., 2006)
EF ↓, SVI ↓, LVSWI ↓, RVSWI ↓, RVSWI ↓, LVVd ↑, LVVs ↑, MMP level ↑ Pig (Goetzenich et al., 2009)
Rapid ventricular pacing Transvenously place a ventricular pacing lead in the apex of the right ventricle CO, HR ↑, SV ↓, Systolic LVP ↓, LVEDP ↑, LVdP/dtmax ↓, LVdP/dtmin ↑, Tau ↑, Mean AoP ↓, Mean CVP ↑, Mean PCWP ↑, Mean PAP ↑, VED ↑, VES ↑, EF, MR ↑, TR ↑, ESWS ↑, EDWS ↑ 1. The cardiovascular hemodynamics and biochemical alterations would progressively revert to near baseline levels after pacing stopped. Dog (Takagaki et al., 2002)
LV Area ↑, FS ↓, EF ↓, LV Free Wall ↓, MR ↑, LVEDP ↑, CO ↓, + dP/dtmax ↓, - dP/dtmax Sheep (Byrne et al., 2002)
HR ↑, MAP, LVEDD ↑, FS ↓, Vcfc ↓, LV peak wall stress ↑, PCWP ↑, PAP ↑, CO ↓ Pig (Spinale et al., 1997)
Transgenic lines MLP-deficient mice LVDD ↑, LVSD ↑, FS ↓, LVDD/LVPWT ↑ 1. Limitations of small animal species in terms of comprehensive physiological measurement Mouse (Yamamoto et al., 2007)
CSQ mice LVEDD ↑, LVESD ↑, FS ↓, mVcfc ↓, HW/BW ↑, LVW/BW ↑, HW/TL ↑, HR, LV dP/dtmax ↓, LV dP/dtmin ↑, LVSP ↓ Mouse (Cho et al., 1999)
Valve disease
Aortic stenosis
Several surgical techniques, including a minimally invasive approach by making a small incision in the proximal sternum, and placement of surgical clips, sutures, or O-rings to prevent blood flow through the aortic arch
EF ↓, LVEDV ↑, LVEDD ↑
1. Inability to easily induce slowly progressive stress overload 2. long duration of the experimental protocol, variability in the individual response to stress overload, and a reduction in the high proportion of constriction due to internalization of the contractile knot. 3. High mortality
Mouse
(Li et al., 2012)
LVSP ↑, LVEDP ↑, LVSWS ↑, LVDWS ↑,PWD, PWS ↑,LVDD ↑, LVSD ↑, LVM ↑, RWT ↑ Rat (Litwin et al., 1995)
LVEDP ↑, LVEDV ↑, EF ↓ Dog (Tagawa et al., 1998)
LVMI ↑, LVIDd ↑, FS ↓ Sheep (Moorjani et al., 2006)
LVW ↑, RVW ↑, LVW/BW ↑, RVW/BW ↑, LVEDP ↑, Myocardial PCr/ATP Ratio↓ 1. Complex surgical method and equipment necessary for open-chest microsurgery. Pig (Ye et al., 2001)
Mitral regurgitation Chordae tendineae cutting HR ↑, Aortic systolic pressure, Forward stroke volume, EDV ↑, Ees ↓, Ees mass↓, Kess ↓, 1. High mortality and complication rates Dog (Spinale et al., 1993)
LV pressure ↓, +dP/dt ↓, LVEDV ↓, Ees ↓, PRSW↓ Sheep (Nielsen et al., 2003)
Inserted a fine needle into LV through the apex of LV, followed by pushing a needle into the mitral valve to puncture and/or tear the mitral leaflets to form MR. EF ↓, EDD ↑, SWT ↓, PWT ↓ 1. Represent limited pathology features of MR in human Rat (Kim et al., 2012)