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.

Imaging of αvβ3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography

“…The size of the pig heart, which is more comparable to the size of the human heart than the heart of rodents, enables the use of clinical scanner and more reliable discrimination between the injured and ischemic myocardial areas. As shown earlier in this model, stent implantation immediately causes severe reduction in blood flow in the target coronary artery as shown by reduced fractional flow reserve, reduced myocardial blood flow during adenosine stress, and rapid collateral growth [19]. Although antithrombotic therapy was continued throughout the study to prevent stent occlusion, areas of organizing injury were detected in 6 animals.…”

“…Coronary stenosis was created in 11 domestic, 3-month old pigs weighing 30–35 kg by implanting a bottleneck stent in the proximal LAD coronary artery as described previously [19]. In addition, a sham group of 4 pigs underwent a catheterization procedure without the stent implantation.…”

“…The bottleneck stent was prepared and implanted as previously described [19]. In brief, an introducer sheath (6F, Cordis, Bridgewater, NJ, USA) was placed percutaneously in the femoral artery.…”

“…We induced stenosis by percutaneous implantation of a bottleneck stent in the proximal left anterior descending (LAD) coronary artery that has been shown to induce severe reduction in myocardial perfusion, rapid collateral formation and some degree of irreversible myocardial injury [19]. We compared [ 68 Ga]NODAGA-RGD uptake in the ischemic myocardium and the remote non-ischemic myocardium as well as in the viable and injured ischemic myocardial areas 2 weeks after the induction of stenosis.…”

Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion

“…Levosimendan has been reported to increase collateral blood flow in dogs 5. Collateral formation is also common in pigs and rapid collateral formation has been demonstrated in a similar model 24 25. Also, anti-inflammatory effects on cardiomyocytes and endothelial cells have shown in vitro 26.…”