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The curative effect of the associated cell transplantation on the rabbit myocardial infarction  [PDF]
Zhicheng Fang, Chang’e Zhou, Xiang Zheng, Boyi Liu, Li Chen, Chunfeng Shen, Pei Liu, Yunfei Huang
Stem Cell Discovery (SCD) , 2013, DOI: 10.4236/scd.2013.34025
Abstract:

Inducing Mesenchymal stem cells to differentiate into cardiomyocycte-like cells and endothelial progenitor cells orientedly and evaluating the curative effect of the associated cell transplantation on the rabbit myocardial infarction (MI). Methods: Mesenchymal stem cells (MSCs) were isolated from the bone marrow of 24 rabbits and cultured in special cell culture medium containing 5-azacytidine (5-AZA), endothelial cell growth supplements (ECGS), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) respectively. The cell transplantation was performed 2 weeks after MI. Rabbits were divided into control group, cardiomyocytes-like cell group, endothelial progenitor cell group and combination group. We used the echocardiography to measure the heart function 2 to 4 weeks after MI, TTC to measure the area of the infarction, flow cytometry to estimate the cell apoptosis. Results: After induced, MSCs were differentiated orientedly into cardiomyocycte-like cells (CLCs) and endothelial progenitor cells (EPCs). CLCs became greater and had a “stick” or “ball” shape. Transmisson electron microscopy showed that the cells had oval nuclei positioned in the central part and well organized myofilaments, atrial granules and mitochomdrion. RT-PCR showed the expression of the atrial natriuretic polypeptide, phospholamban and myosin heavy chain in CLCs. EPCs formed confluent one-celled layer which showed a cobblestone shape by phase-contrast microscope. The expression of CD133 in EPCs was much at first and then descended gradually. Compared with the control group, cell transplantation could improve the heart function, reduce the size of MI, decrease the left ventricular end systole diameter and end diastolic diameter, suppressed cell apoptosis. The curative effect of cell transplantation was better in the associated-cell group than in the single-cell transplantation group (LVEF: 32.49% ± 1.29% vs 53.22% ± 2.13% vs 56.91% ±

Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases
Tsutomu Kobayashi,Takashi Ito,Masashi Shiomi
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/406473
Abstract: Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL) receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI) rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.
Effects of simvastatin on ion channel currents in ventricular myocytes from rabbit with acute myocardial infarction

Chao Ding,Li Yang,Huixiao Chen,Junxia Li,Yuying Zhao,Jie Li,Jie Wang,Xianghua Fu,

老年心脏病学杂志(英文版) , 2008,
Abstract: Objective To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes after acute myocardial infarction (AMI,so as to explore the ionic mechanism of statin treatment for antiarrhythmia.Methods Fourty-five New Zeland rabbits were randomly divided into three groups:AMI group,simvastatin intervention group (statin group) and sham-operated control group (CON).Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simv...
Myocardial infarction in children: Two interesting cases
Suryawanshi Suresh,Das Braj,Patnaik Amar
Annals of Pediatric Cardiology , 2011,
Abstract: Myocardial infarction in children is extremely rare and can have various etiologies. The following two case reports highlight rare but important causes of myocardial infarction in children.
Heroin Abuse and Myocardial Infarction
Ersan TATLI
Trakya Universitesi Tip Fakultesi Dergisi , 2010,
Abstract: Information concerning acute myocardial infarction after heroin usage is limited and the actual mechanism of heroin-induced myocardial infarction is not well known. Only one report has been described noting the association between usage heroin and acute myocardial infarction in a young man with normal coronary arteries. We also reported a patient with normal coronary arteries and acute myocardial infarction after heroin abuse.
Heterogeneous of potassium currents in free wall myocytes from the infarcted rabbit ventricle and regression effects of imidapril
Yang Li,Shiwen Wang,Yi Wen,Bin Xu,Yuqi Liu,Zongbin Li,Xinhua Wang,
Yang Li
,Shiwen Wang,Yi Wen,Bin Xu,Yuqi Liu,Zongbin Li,Xinhua Wang

老年心脏病学杂志(英文版) , 2008,
Abstract: Objective To define the heterogeneous changes of ion channels in the noninfarcted myocardium after myocardial infarction in rabbit and effects of imidapril.Mehods Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 wk.Myocytes were isolated from subendocardial,midmyocardial and subepicardial regions of the noninfarcted left ventricular free wall.Ion currents were recorded with whole-cell patch clamp way.Results The densities of the transient outward K currents (I to) and the inward rectifier K currents (I K1) were greatly reduced in midmyocardium and subepicardium while two currents reduced gently in subendocardium.The densities of the delayed rectifier K currents (I K) were reduced in noninfarcted three layers similarly.Imidapril could reverse the changes of membrane currents in healed myocardial infarction cells and depress the dispersion of repolarization.Conclusions The heterogeneities of K currents are enhanced in noninfarcted area.Normalization of heterogeneous changes of repolarization after treatment with imidapril was observed.
Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit’s Nictitating Membrane Response  [PDF]
Bernard G. Schreurs,Desheng Wang,Carrie A. Smith-Bell,Lauren B. Burhans,Roger Bell,Jimena Gonzalez-Joekes
International Journal of Alzheimer's Disease , 2012, DOI: 10.1155/2012/732634
Abstract: A rabbit model of Alzheimer’s disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit’s nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory. 1. Introduction In rabbits fed 2% cholesterol for as little as eight weeks, there are as many as sixteen different indices of pathology that are similar to those seen in Alzheimer’s Disease (AD) including intracellular and extracellular Aβ, breaches of the blood brain barrier, activation of microglia, apoptosis, increased levels of Apolipoprotein E, phosphorylated tau protein, changes in the cerebrovasculature, and increases in ventricular volume [1–12]. Coinciding with these changes in brain pathology, there have been reports of detrimental effects on learning [6, 13–16]. Nevertheless, research with this and other animal models suggests that modifying dietary cholesterol can in many cases improve learning and memory. For instance, increasing cholesterol in young DBA/2 mutant mice improves performance on the Morris water maze—a spatial learning task that is normally impaired in this mutant [17, 18]. Feeding cholesterol to young, normal rats also improves performance on the Morris water maze [19]. Feeding cholesterol to rats that are either deficient in cholesterol or have cholesterol synthesis blocked reverses problems with learning and memory [20–23]. We have also shown that feeding rabbits cholesterol can facilitate classical
Transauricular embolization of the rabbit coronary artery for experimental myocardial infarction: comparison of a minimally invasive closed-chest model with open-chest surgery
Konstantinos Katsanos, Sofoklis Mitsos, Efstratios Koletsis, Vassiliki Bravou, Dimitris Karnabatidis, Fevronia Kolonitsiou, Athanassios Diamantopoulos, Dimitrios Dougenis, Dimitris Siablis
Journal of Cardiothoracic Surgery , 2012, DOI: 10.1186/1749-8090-7-16
Abstract: New Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD) coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG), cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP) measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining.In total, 38 subjects underwent EMI with a surgical (n = 17) or endovascular (n = 21) approach. ST-segment elevation (1.90 ± 0.71 mm) occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68) within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05). Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68).The proposed model of transauricular coronary coil embolization avoids thoracotomy and major surgery and may be an equally reliable and reproducible platform for the experimental study of myocardial ischemia.Ischemic coronary artery disease is a major cause of morbidity and mortality. Appropriate animal models are essential in order to investigate the mechanisms of myocardial infarction and develop new therapeutic interventions. During the last years, experimental myocardial ischemia (EMI) has been one of the most extensively studied topics in modern
Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study
Rikke S?rensen, Steen Z Abildstrom, Peter Weeke, Emil L Fosb?l, Fredrik Folke, Morten L Hansen, Peter R Hansen, Jan K Madsen, Ulrik Abildgaard, Lars K?ber, Henrik E Poulsen, Christian Torp-Pedersen, Gunnar H Gislason
BMC Cardiovascular Disorders , 2010, DOI: 10.1186/1471-2261-10-6
Abstract: Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.Clopidogrel reduces coronary ischemic events in patients with acute coronary syndrome[1] and after percutaneous coronary intervention (PCI) where the beneficial effect is evident within the first 24 hours of treatment initiation[2-4]. In the past 5 years there has been a clear tendency to recommend increased duration of clopidogrel treatment. Current guidelines recommend 12 months of treatment for all patients after non-ST-elevation myocardial infarction, ST-elevation myocardial infarction and after treatment with PCI, in the absence of a high risk of bleeding[5-7]. The optimal duration of clopidogrel treatment is a major clinical issue, as clopidogrel, in addition to the desired anti-thrombotic effect, poses a considerable risk of bleeding. Premature cessation has been associated with increased risk of thrombotic events, including s
Cardioprotective Effects of Exogenous and Endogenous Hydrocortisone in the Rabbit Model of Ischemia-Reperfusion
Davarian,Ali; Khori,Vahid; Nayebpour,Mohsen;
International Journal of Morphology , 2010, DOI: 10.4067/S0717-95022010000300001
Abstract: reducing the infarct size in acute myocardial infarction is one of the most important goals driving new drug research and development. during the last two decades, many clinical studies have found cardioprotective effects of corticosteroids, but their exact role in ischemic preconditioning remains questionable. the aim of the present study was to determine the protective effects of hydrocortisone sodium succinate on myocardial preconditioning in rabbit hearts. twenty-four male new zealand rabbits were divided randomly & equally in four groups: 1) control, 2) infarct, 3) ischemic preconditioning (ip) and 4) hydrocortisone (hyd). the hyd group received 50mg/kg hydrocortisone 45min before major ischemia. serum levels of cardiac troponin-t(ctnt) and cortisole were measured before and after the protocols. triphenyl-tetrazolium chloride staining was used to determine the infarcted area. in the present study, exogenous hydrocortisone decreased infarct size by 53% in comparison to the infarct group. serum level of cortisole was increased in the ip and hyd groups, and was significant in the hyd group (p<0.01). an increasing trend in cortisole level was associated with a decreasing trend in infarct size and ctnt in the ip and hyd groups (p>0.01). in conclusion, we showed that hydrocortisone has cardioprotective effects when injected before the onset of myocardial infarction. in addition, we have proposed for the first time that endogenous hydrocortisone may play a role in ischemic preconditioning phenomena.
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