title: The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs.
abstract: A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one- and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4-5 wk. Ejection fraction (EF), infarct size, collateral growth, and myocardial perfusion were assessed. Pigs were given antiarrhythmic medication to prevent sudden death. The occlusion time of the bottleneck stent and the timing of myocardial infarction could be modulated by the duration of antiplatelet medication. Fractional flow reserve measurements and positron emission tomography imaging showed severe ischemia after bottleneck stenting covering over 50% of the left ventricle in the proximal LAD model. Complete coronary occlusion was necessary for significant collateral growth, which mostly had occurred already during the first wk after the stent occlusion. Dynamic and competitive collateral growth patterns were observed. EF declined from 64 to 41% in the LCX model and to 44% in the LAD model 4 wk after stenting with 12 and 21% infarcted left ventricle in the LCX and LAD models, respectively. The mortality was 32 and 37% in the LCX and LAD models but very (71%) high in the two-vessel disease model. The implantation of a novel bottleneck stent in the proximal LAD or LCX is a novel porcine model of reversible myocardial ischemia (open stent) and ischemic heart failure (occluded stent) and is feasible for the development of new therapeutic approaches.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland;
authors.forename: Tuomas T
authors.initials: TT
authors.lastname: Rissanen
authors.forename: Jussi
authors.initials: J
authors.lastname: Nurro
authors.forename: Paavo J
authors.initials: PJ
authors.lastname: Halonen
authors.forename: Miikka
authors.initials: M
authors.lastname: Tarkia
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Markus
authors.initials: M
authors.lastname: Rannankari
authors.forename: Krista
authors.initials: K
authors.lastname: Honkonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Pietilä
authors.forename: Olli
authors.initials: O
authors.lastname: Leppänen
authors.forename: Antti
authors.initials: A
authors.lastname: Kuivanen
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002908:Chronic Disease; D003097:Collateral Circulation; D017023:Coronary Angiography / Q000379:methods; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D005240:Feasibility Studies; D053805:Fractional Flow Reserve, Myocardial; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000473:pathology; D062645:Percutaneous Coronary Intervention / Q000295:instrumentation*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011138:Polytetrafluoroethylene; D011474:Prosthesis Design; D015607:Stents; D013318:Stroke Volume; D034421:Sus scrofa; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016277:Ventricular Function, Left
chemical_list: D000889:Anti-Arrhythmia Agents; D010975:Platelet Aggregation Inhibitors; D011138:Polytetrafluoroethylene
keywords: angiogenesis; arteriogenesis; collateral growth; ischemia; myocardium