Rabbit models of heart disease

Pogwizd, Steven M.; Bers, Donald M.

doi:10.1016/j.ddmod.2009.02.001

Cited by 38 publications

(45 citation statements)

References 103 publications

(119 reference statements)

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“…We sought to examine the antiarrhythmic effects of CaMKII inhibition in a HF model that more closely mimics human HF, and in a species whose AP and calcium transient characteristics are more similar to human. [7]…”

Section: Discussionmentioning

confidence: 99%

“…It is well established that mice exhibit profound differences in action potential (AP) shape, ionic currents, calcium handling and contractile protein isoforms compared to either rabbit or human hearts. [6, 7] Thus, in vivo tests of CaMKII inhibition are lacking in clinically relevant animal models of HF. We have extensively characterized molecular mechanisms underlying CaMKII activation in our well-characterized arrhythmogenic model of nonischemic HF, including showing that enhanced CaMKII activation and CaMKII-dependent phosphorylation of the cardiac ryanodine receptor (RyR2) are involved in enhanced diastolic sarcoplasmic reticulum (SR) calcium leak in HF.…”

Section: Introductionmentioning

confidence: 99%

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Reduced Arrhythmia Inducibility With Calcium/Calmodulin-dependent Protein Kinase II Inhibition in Heart Failure Rabbits

Hoeker

Hanafy

Oster

et al. 2016

Journal of Cardiovascular Pharmacology

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Rationale Calcium/calmodulin-dependent protein kinase II (CaMKII) is activated in heart failure (HF) and can contribute to arrhythmias induced by β-adrenergic receptor-mediated sarcoplasmic reticulum calcium leak. Objective To evaluate the effect of CaMKII inhibition on ventricular tachycardia (VT) induction in conscious HF and naïve rabbits. Methods and Results Nonischemic HF was induced by aortic insufficiency and constriction. Electrocardiograms were recorded in rabbits pretreated with vehicle (saline) or the CaMKII inhibitor KN-93 (300 μg/kg); VT was induced by infusion of increasing doses of norepinephrine (NE, 1.56-25 μg/kg/min) in naïve (n = 8) and HF (n = 7) rabbits. With saline, median VT dose threshold in HF was 6.25 versus 12.5 μg/kg/min NE in naïve rabbits (p = 0.06). Pretreatment with KN-93 significantly increased VT threshold in HF and naïve rabbits (median = 25 μg/kg/min, p < 0.05 versus saline for both groups). Mean cycle length of VT initiation was shorter in HF (221 ± 20 ms) than naïve (296 ± 23 ms, p < 0.05) rabbits with saline; this difference was not significant after treatment with KN-93. Conclusions KN-93 significantly reduced arrhythmia inducibility and slowed initiation of VT, suggesting that CaMKII inhibition may have antiarrhythmic effects in the failing human heart.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduced Arrhythmia Inducibility With Calcium/Calmodulin-dependent Protein Kinase II Inhibition in Heart Failure Rabbits

Hoeker

Hanafy

Oster

et al. 2016

Journal of Cardiovascular Pharmacology

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“…M. Hoeg, et al, 1996); and (3) those proteins that may participate in the pathogenesis of atherosclerosis (matrix metalloproteinase-12 (Liang, et al, 2006), 15-lipoxygenase (Shen, et al, 1996), C-reactive protein (Koike, Kitajima, Yu, Nishijima, et al, 2009) and vascular endothelial growth factor (Kitajima, et al, 2005) (Table 3). Tg rabbits have also been used for the study of human heart diseases, such as LQT syndrome (Brunner, et al, 2008), hypertrophic cardiomyopathy (Marian, et al, 1999) and tachycardia-induced cardiomyopathy (Suzuki, et al, 2009) because, compared with rodents, the rabbit heart is structurally and functionally more similar to that of humans (Table 4) (King, et al, 2010; Pogwizd & Bers, 2008; Tanaka, et al, 2008). …”

Section: Transgenic Rabbitsmentioning

confidence: 99%

Rabbit models for the study of human atherosclerosis: From pathophysiological mechanisms to translational medicine

Fan

Kitajima

Watanabe

et al. 2015

Pharmacology & Therapeutics

279

283

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Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits.

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“…1,2 The rabbit model is frequently used for investigating MI. 3 Compared to smaller animals, rabbit hearts bear a greater resemblance to that of humans, including increased similarity in ventricular action potential morphology, 4 calcium handling, 5 and myosin heavy chain composition. 6 Additionally, rabbits and humans both have limited collateral cardiac circulation.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Study of Cardiac Remodelling in Rabbits Following Infarction

Wang¹,

Popović²,

Efimov³

et al. 2012

Canadian Journal of Cardiology

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Background Cardiac remodeling following myocardial infarction (MI) is a complex, dynamic process. There have been few longitudinal studies of these changes. Methods Two-dimensional transthoracic echocardiography was performed on 20 rabbits: before and 1, 2, 4, 8, and 12 weeks after MI (n=14) and twice for controls (n=6). Chronic left ventricular (LV) infarct size was histologically characterized and correlated with mechanical function. A linear mixed model was used to analyze longitudinal and infarct size related changes in LV end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), sphericity, circumferential strain, and wall motion score index (WMSI). Results Mean LV infarct size was 28.9±9.3%. After MI, rapid remodeling occurred in LVESV, LVEF, and sphericity for 2 weeks and LVEDV for 4 weeks, with slower changes afterwards. LV infarct size correlated with LVESV (r=0.76), LVEDV (r=0.71), and LVEF (r=0.69). Larger infarcts resulted in greater LVESV dilation (p=0.04) and faster LVEDV (p<0.01), LVEF (p<0.01) and sphericity (p<0.01) remodeling. Apical global circumferential strain and WMSI increased for 1 week then stabilized, regardless of infarct size, and apical global circumferential strain was correlated with apical infarction (r=0.58). Additionally, regional circumferential strain decreased in segments with severe (>80%) infarction more quickly (p<0.01) and by a greater degree (p=0.04) compared to segments with minor (<20%) infarction. Conclusions The most dynamic remodeling of cardiac function in this model occurred during the first 4 weeks, stabilizing thereafter, with changes maintained up to 12 weeks. Infarct size affected both the early rate and long-term extent of mechanical remodeling.

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Rabbit models of heart disease

Cited by 38 publications

References 103 publications

Reduced Arrhythmia Inducibility With Calcium/Calmodulin-dependent Protein Kinase II Inhibition in Heart Failure Rabbits

Reduced Arrhythmia Inducibility With Calcium/Calmodulin-dependent Protein Kinase II Inhibition in Heart Failure Rabbits

Rabbit models for the study of human atherosclerosis: From pathophysiological mechanisms to translational medicine

Longitudinal Study of Cardiac Remodelling in Rabbits Following Infarction

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