Preclinical modeling and multimodality imaging of chronic myocardial infarction in minipigs induced by novel interventional embolization technique

BackgroundThis study was designed to establish a chronic myocardial infarction (MI) model in minipigs with a novel coronary sequential balloons-sponge embolism technique.MethodsEighteen healthy minipigs (25–30 kg) were randomly divided into three groups for left anterior descending artery (LAD) occlusion: conventional balloon occlusion group (BO group, temporary balloon occlusion for 60 mins), half-balloon embolism group (HB group), and sequential balloon-balloon-sponge embolism group (BBS group, two half-balloons with one sponge as the embolism clot). The incidence of ventricular fibrillation (VF), total mortality, operating time, and vascular recanalization 3 months post-MI was recorded and compared. Echocardiography, multimodality nuclear medical imaging, and histology staining were applied for the evaluation of infarction.ResultsThirteen out of 18 minipigs survived after the operation, while 5 animals died with VF (3 in the BO group, 1 in the HB group, and 1 in the BBS group), with an 83.3 % (5/6 minipigs) acute procedural survival rate in embolism groups. The operating duration was 60.0 ± 0.5 mins, 21.4 ± 5.2 mins, and 31.2 ± 4.7 mins in the three groups, respectively. LAD recanalization was found in three animals of the HB group but none in the BBS group by angiography follow-up. The infarct sizes were more stable and larger in the HB group and BBS group than that in the BO group (P < 0.05, n = 13).ConclusionsThe method of sequential balloons-sponge embolization could induce myocardial infarction with consistent and sustained embolization and gain higher operation success rate and better repeatability in minipigs, which holds a promising method for preclinical MI study.

[1]  F. Cao,et al.  Percutaneous Intramyocardial Delivery of Mesenchymal Stem Cells Induces Superior Improvement in Regional Left Ventricular Function Compared with Bone Marrow Mononuclear Cells in Porcine Myocardial Infarcted Heart , 2015, Theranostics.

[2]  P. Pattany,et al.  Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity , 2009, Proceedings of the National Academy of Sciences.

[3]  R. Lancashire,et al.  Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study , 2001, The Lancet.

[4]  Bernadette A. Thomas,et al.  Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2015, The Lancet.

[5]  Stephan G. Nekolla,et al.  Integration of Infarct Size, Tissue Perfusion, and Metabolism by Hybrid Cardiac Positron Emission Tomography/Computed Tomography: Evaluation in a Porcine Model of Myocardial Infarction , 2009, Circulation. Cardiovascular imaging.

[6]  A. Yeung,et al.  In vivo porcine model of reperfused myocardial infarction: In situ double staining to measure precise infarct area/area at risk , 2008, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[7]  T. Reffelmann,et al.  A novel minimal-invasive model of chronic myocardial infarction in swine , 2004, Coronary artery disease.

[8]  Fumiaki Ikeno,et al.  The Representative Porcine Model for Human Cardiovascular Disease , 2010, Journal of biomedicine & biotechnology.

[9]  Alan D. Lopez,et al.  The Global Burden of Disease Study , 2003 .

[10]  R. Lederman,et al.  Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction. , 2008, European heart journal.

[11]  M. Amorim,et al.  Surgical porcine myocardial infarction model through permanent coronary occlusion. , 2011, Comparative medicine.

[12]  E. Marbán,et al.  Validation of Contrast-Enhanced Magnetic Resonance Imaging to Monitor Regenerative Efficacy After Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction , 2013, Circulation.

[13]  Bernadette A. Thomas,et al.  Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2015, The Lancet.

[14]  Mark D. Huffman,et al.  AHA Statistical Update Heart Disease and Stroke Statistics — 2012 Update A Report From the American Heart Association WRITING GROUP MEMBERS , 2010 .

[15]  G. Pasterkamp,et al.  Cardiac Function in a Long-Term Follow-Up Study of Moderate and Severe Porcine Model of Chronic Myocardial Infarction , 2015, BioMed research international.

[16]  Celso K. Takimura,et al.  Development of a closed‐artery catheter‐based myocardial infarction in pigs using sponge and lidocaine hydrochloride infusion to prevent irreversible ventricular fibrillation , 2014, Physiological reports.

[17]  I. Repa,et al.  Overview of large animal myocardial infarction models (review). , 2012, Acta physiologica Hungarica.

[18]  E. Diethrich,et al.  A percutaneous swine model of myocardial infarction. , 2006, Journal of pharmacological and toxicological methods.

[19]  Rolf W. Günther,et al.  Minimally Invasive Close-Chest Method for Creating Reperfused or Occlusive Myocardial Infarction in Swine , 2005, Investigative radiology.

[20]  F. Prósper,et al.  Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction. , 2010, European heart journal.

[21]  B. Whitson,et al.  A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets , 2013, BioMed research international.

[22]  B. Hamm,et al.  A minimally invasive method for induction of myocardial infarction in an animal model using tungsten spirals , 2009, The International Journal of Cardiovascular Imaging.

[23]  K. Cao,et al.  Effects of different LAD-blocked sites on the development of acute myocardial infarction and malignant arrhythmia in a swine model. , 2014, Journal of thoracic disease.

[24]  M. Jeong,et al.  A porcine model of ischemic heart failure produced by intracoronary injection of ethyl alcohol , 2011, Heart and Vessels.

[25]  A. Heldman,et al.  Myocardial infarction and intramyocardial injection models in swine , 2012, Nature Protocols.

[26]  A. Amodeo,et al.  A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease , 2013, BioMed research international.

[27]  W. Boyd,et al.  Embolization of the first diagonal branch of the left anterior descending coronary artery as a porcine model of chronic trans-mural myocardial infarction , 2015, Journal of Translational Medicine.

[28]  F. Sánchez-Margallo,et al.  Development of a Closed Chest Model of Chronic Myocardial Infarction in Swine: Magnetic Resonance Imaging and Pathological Evaluation , 2013, ISRN cardiology.

[29]  G. Rioufol,et al.  A minimally-invasive closed chest myocardial occlusion-reperfusion model in rhesus monkeys (Macaca mulatta): monitoring by contrast-enhanced ultrasound imaging , 2012, The International Journal of Cardiovascular Imaging.

[30]  Christoph Dommke,et al.  Defining the Transmurality of a Chronic Myocardial Infarction by Ultrasonic Strain-Rate Imaging: Implications for Identifying Intramural Viability An Experimental Study , 2003, Circulation.