Chronic Heart Failure Model Induced by Coronary Embolization in Sheep

Asaio Journal, 2013

A major limitation in the development of mechanical circulatory support (MCS) devices has been the lack of a clinically relevant, stable, and reproducible large animal chronic heart failure (HF) model. High mortality rates have been reported with large animal chronic HF models. In this study, methods of medical management to improve survival rate (SR) were investigated. Chronic ischemic HF (IHF) was induced in Jersey calves using a microembolization technique via fluoroscopyguided injection of 90 μm microspheres into the coronary vasculature. Animals were divided into 1) Control-multiple embolization procedures with conservative therapy (n = 9); 2) treatment group 1 (TG1)-single embolization procedure with moderately aggressive therapy (n = 8); and 3) TG2-single embolization procedure with aggressive medical management (n = 20). The groups were not randomized with data analyzed retrospectively. Mean SR, body condition score, body weight, hemodynamic, echocardiography, and histopathology indices were recorded up to 60 days postembolization. SR improved from 56% (Control) to 75% (TG1) and 90% (TG2) using an aggressive medical management regimen of analgesia, diuretics, beta-blockade, antiarrhythmics, vasodilators, and inotropes. These findings support the hypothesis that a single coronary microembolization procedure and aggressive medical therapy produces a clinically relevant chronic IHF model with a significantly higher SR than conservative medical therapy.

BioMed research international, 2015

Background. Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed. Methods. Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations. Results. Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (-17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (-5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up. Conclusion. Two models of chronic MI, represent...

Cardiovascular Research, 2004

Objective: It has been suggested that in some settings, heart failure (HF) may occur with normal ejection fraction (EF) as a consequence of undetected systolic dysfunction. However, others have argued that this can only occur in the presence of diastolic dysfunction. We therefore sought to determine the contribution of diastolic dysfunction in an animal model of HF with normal EF. Methods and results: Limited myocardial injury was induced in 21 dogs chronically instrumented to measure hemodynamics and LV properties by daily coronary microembolization (f 115 Am beads) until LV end diastolic pressure (LVEDP) was z 16 mm Hg. Nine dogs developed HF within 16 F 6 days (LVEDP 12 F 2 vs. 21 F 2 mm Hg, p < 0.001) with no significant change in dP/dt max (2999 F 97 vs. 2846 F 189 mm Hg/s), mean arterial pressure (103 F 4 vs. 100 F 4 mm Hg), EF (57 F 5% vs. 53 F 4%) or E es (end-systolic elastance, 3.1 F 0.9 vs. 2.9 F 0.8 mm Hg/ml) but with an f 10 ml increase in V o (14 F 12 vs. 25 F 16 ml; p < 0.01). The EDPVR and time constant of relaxation (s, 25 F 3 vs. 28 F 3 ms) did not change significantly. These animals were hemodynamically stable out to 3 1/2 months. Neurohormonal activation occurred (elevations of NE, AngII, BNP) and there was intravascular volume expansion by f 16% (p < 0.05). Conclusions: A small amount of myocardial injury can lead to neurohormonal activation with intravascular volume expansion and elevation of LVEDP in the absence of reductions in dP/dt max or EF and without diastolic dysfunction. Thus, HF with preserved EF does not a priori equate with diastolic heart failure.

Animals

A chronic model of acute myocardial infarction was developed to study the mechanisms involved in adverse postinfarction ventricular remodeling. In an acute myocardial infarction (AMI), the left circumflex coronary artery of New Zealand White rabbits (n = 9) was occluded by ligature for 1 h, followed by reperfusion. A specific care protocol was applied before, during, and after the intervention, and the results were compared with those of a sham operated group (n = 7). After 5 weeks, programmed stimulation and high-resolution mapping were performed on isolated and perfused hearts using the Langendorff technique. The infarct size determined by 2,3,5-triphenyltetrazolium chloride inside of the area at risk (thioflavin-S) was then determined. The area at risk was similar in both groups (54.33% (experimental infarct group) vs. 58.59% (sham group), ns). The infarct size was 73.16% as a percentage of the risk area. The experimental infarct group had a higher inducibility of ventricular arr...

ILAR Journal, 2011

Volume 52(e16-e21) -2011 ILAR e-Journal is the online, periodic, peer-reviewed publication Abstract Studies on cardiac regeneration require large mammalian models of dilated cardiomyopathy (DCM) after acute myocardial infarction (AMI), and pig and sheep models are increasingly used in this field of preclinical research. Given the large interindividual variability in ovine left anterior descending artery (LAD) anatomy, protocols based on the coronary arteries to be ligated often lead to significant variation in infarct sizes and hence to heterogeneous results, ranging from no ventricular remodeling to acute, lethal left ventricular (LV) failure. We designed an ovine model of postinfarction DCM based on estimated infarct size rather than on a predetermined menu of coronary artery ligatures. In seven adult sheep we induced an anterolateral AMI of approximately 25% of the LV mass by ligating the branches of the LAD that, by visual inspection, would lead to such an infarct size. In 10 to 12 weeks, LV end-diastolic volume more than doubled and LV end-systolic volume almost tripled. LV ejection fraction decreased dramatically, as did LV percent fractional shortening and LV percent wall thickening. Infarct size (planimetry) was approximately 25% of the LV endocardial surface. We conclude that in sheep, an anterolateral AMI of approximately 25% of the LV massregardless of the coronary branches ligated to attain that infarct size-results in a model of postinfarction DCM that may prove useful in preclinical research on myocardial regeneration.

American Journal of Physiology-heart and Circulatory Physiology, 1997

The Annals of Thoracic Surgery, 2002

An ovine model of postinfarction dilated cardiomyopathy http://ats.ctsnetjournals.org/cgi/content/full/74/3/753 on the World Wide Web at: The online version of this article, along with updated information and services, is located Print ISSN: 0003-4975; eISSN: 1552-6259. Southern Thoracic Surgical Association.

Clujul Medical, 2014

Journal of Surgical Research, 2010

Over the past century, numerous animal models have been developed in an attempt to understand myocardial and vascular injury. However, the successful translation of results observed in animals to human therapy remains low. To understand this problem, we present several animal models of cardiac and vascular injury that are of particular relevance to the cardiac or vascular surgeon. We also explore the potential clinical implications and limitations of each model with respect to the human disease state. Our results underscore the concept that animal research requires an in-depth understanding of the model, animal physiology, and the potential confounding factors. Future outcome analyses with standardized animal models may improve translation of animal research from the bench to the bedside. Ó

Comparative Medicine, 2018

The prevalence of cardiovascular disease (CVD) in humans achieved global significance over the past 2 decades. In the Asian Pacific region, ischemic heart disease accounted for an estimated 7.3 million deaths in 2008, whereas CVD, in general, is the leading cause of death in the Caribbean region. In addition, ischemic heart disease is responsible for 5.2% of the worldwide burden due to heart disease. 14 Many risk factors including diet, tobacco use, obesity, diabetes mellitus, and hypertension predispose the human population to CVD, but occupational hazards such as ambient pollution by factories coupled with debilitating preexisting conditions such as HIV-AIDS are important contributors also. Pigs and sheep, which have poor coronary collateral circulation, are 2 important animal models used to study ischemic heart disease. Depending on the nature of the study, sheep may be chosen over pigs, which are prone to ventricular arrhythmia and have a tendency to develop irreversible ventricular fibrillation. Sheep are used for diverse cardiac studies including evaluation of valvular prostheses and research involving myocardial ischemia. In addition, the sheep heart is similar to that of humans both in terms of size and the composition of cardiomyocytes. The current study provides valuable insights regarding the use of infarction scar size in conjunction with left ventricular ejection fraction as a useful predictor of advanced left ventricular dysfunction.