Fluoroscopy Guided Minimally Invasive Swine Model of Myocardial Infarction by Left Coronary Artery Occlusion for Regenerative Cardiology.

Background Despite the recent advancements in the cardiac regenerative technologies, the lack of an ideal translationally relevant experimental model simulating the clinical setting of acute myocardial infarction (MI) hurdles the success of cardiac regenerative strategies. Methods We developed a modified minimally invasive acute MI model in Yucatan miniswine by catheter-driven controlled occlusion of LCX branches for regenerative cardiology. Using a balloon catheter in three pigs, the angiography guided occlusion of LCX for 10-15 minutes resulted in MI induction which was confirmed by the pathological ECG changes compared to the baseline control. Results Ejection fraction was considerably decreased post-procedure compared to the baseline. Importantly, the highly sensitive MI biomarker Troponin I was significantly increased in post-MI and follow-up groups along with LDH and CCK than the baseline control. The postmortem infarct zone tissue displayed the classical features of MI including ECM disorganization, hypertrophy, inflammation, and angiogenesis confirming the MI at the tissue level. Conclusions The present model possesses the advantage of minimal mortality, simulating the pathological features of clinical MI and the suitability for injectable regenerative therapies suggesting the translational significance in regenerative cardiology.

[1]  Rizwan Kalani,et al.  Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association , 2022, Circulation.

[2]  D. Agrawal,et al.  Translational model of vein graft failure following coronary artery bypass graft in atherosclerotic microswine , 2021, General Thoracic and Cardiovascular Surgery.

[3]  R. Graham,et al.  Mechanism-Based Cardiac Regeneration Strategies in Mammals , 2021, Frontiers in Cell and Developmental Biology.

[4]  Y. Shudo,et al.  Current Status and Limitations of Myocardial Infarction Large Animal Models in Cardiovascular Translational Research , 2021, Frontiers in Bioengineering and Biotechnology.

[5]  M. Gyöngyösi,et al.  Large Animal Models of Cell-Free Cardiac Regeneration , 2020, Biomolecules.

[6]  J. Vieira,et al.  Model organisms at the heart of regeneration , 2019, Disease Models & Mechanisms.

[7]  S. Tohyama,et al.  Age-Appropriateness of Porcine Models Used for Cell Transplantation , 2018, Cell transplantation.

[8]  M. Mohammad,et al.  Culprit vessel: impact on short-term and long-term prognosis in patients with ST-elevation myocardial infarction , 2018, Open Heart.

[9]  D. Taggart,et al.  The potential role of external venous supports in coronary artery bypass graft surgery† , 2018, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[10]  Ying Liu,et al.  To develop a novel animal model of myocardial infarction: A research imperative , 2018, Animal models and experimental medicine.

[11]  C. Swingen,et al.  Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery , 2017, The Journal of thoracic and cardiovascular surgery.

[12]  D. Agrawal,et al.  TREM-1, HMGB1 and RAGE in the Shoulder Tendon: Dual Mechanisms for Inflammation Based on the Coincidence of Glenohumeral Arthritis , 2016, PloS one.

[13]  R. Kelly,et al.  Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery , 2016, Journal of Cardiovascular Translational Research.

[14]  F. Sánchez-Margallo,et al.  Common swine models of cardiovascular disease for research and training , 2016, Lab Animal.

[15]  M. Biddle,et al.  A report from the American Heart Association Council on Cardiovascular and Stroke Nursing. , 2015, The Journal of cardiovascular nursing.

[16]  R. Levine,et al.  Characterizing preclinical models of ischemic heart failure: differences between LAD and LCx infarctions. , 2014, American journal of physiology. Heart and circulatory physiology.

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

[18]  M. Jayabalan,et al.  Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure , 2012, Biomatter.

[19]  J. Cho,et al.  Clinical outcomes of acute myocardial infarction with occluded left circumflex artery. , 2011, Journal of cardiology.

[20]  A. Corson,et al.  Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview. , 2010, Animal : an international journal of animal bioscience.

[21]  E. Ruttmann,et al.  Training models for coronary surgery. , 2007, The heart surgery forum.

[22]  Yin Wu,et al.  A simple and fast experimental model of myocardial infarction in the mouse. , 2006, Texas Heart Institute journal.

[23]  G. Gross,et al.  Acute and chronic administration of disodium disuccinate astaxanthin (CardaxTM) produces marked cardioprotection in dog hearts , 2005, Molecular and Cellular Biochemistry.

[24]  R. Shofti,et al.  The sheep as a model for coronary artery bypass surgery , 2004, Laboratory animals.

[25]  J. Fleg,et al.  Left ventricular remodeling with age in normal men versus women: novel insights using three-dimensional magnetic resonance imaging. , 2002, The American journal of cardiology.

[26]  W. Lew,et al.  Functional consequences of acute anterior vs. posterior wall ischemia in canine left ventricles. , 1988, The American journal of physiology.