Critical Single Proximal Left Arterial Descending Coronary Artery Stenosis to Mimic Chronic Myocardial Ischemia: A New Model Induced by Minimal Invasive Technology

Abstract

Background/Aims: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. Methods: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. Results: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 ± 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 ± 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. Conclusion: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs

“…In another study 68% of pigs developed a coronary stenosis of over 75% by 6 wk, but myocardial ischemia and the formation of collaterals were not reported (26). A custommade stent composed of 0.3-mm-thick copper wire placed in the proximal LAD caused over 90% stenosis by ϳ3 wk in half of the pigs (9). LVEF was reduced from 68 to 25% 3 wk after the operation at the cost of a 36% mortality rate.…”

“…A gradually evolving coronary stenosis has been generated by reactive intimal hyperplasia by polymer-or copper-coated stents (6,9,20,26). Implantation of a copper-coated stent in the mid LCX caused chronic total occlusion within 4 wk with a low mortality rate of 6% and formation of bridging collaterals growing over the occlusion (20).…”

“…Surgical dissection of the carotid artery has often been used for arterial access in pigs (4,18,24,26). However, we used the normal percutaneous femoral approach because it is faster, causes less radiation to the operator, is less painful for the animals, and allows follow-up angiographies (2,9,13). Femoral introducer sheaths (12 cm in length; Cordis, Bridgewater, NJ) were placed percutaneously in the right femoral artery (6-F) and vein (4-F) using the standard Seldinger's technique.…”

“…The Femostop device (St. Jude Medical, St. Paul, MN) was used to secure hemostasis according to the manufacturer's instructions. Attention was paid to careful hemostasis because bleeding complications are often fatal in pigs with the use of DAPT (9,13).…”

Local Transient Myocardial Liposomal Gene Transfer of Inducible Nitric Oxide Synthase Does Not Aggravate Myocardial Function and Fibrosis and Leads to Moderate Neovascularization in Chronic Myocardial Ischemia in Pigs

“…Twenty‐three German Landrace pigs of either sex weighing 30–35 kg were subjected to percutaneous implantation of a stent into the left anterior descending (LAD) artery immediately distal to the first septal branch. Studies from our laboratory have shown that this procedure is associated with the formation of a gradually evolving severe coronary artery (in‐stent) stenosis leading, within the weeks following the intervention, to ventricular fibrosis, myocardial hibernation, and systolic dysfunction [15]. Briefly, quantitative vascular angiography of the LAD was performed and a matching percutaneous transluminal coronary angioplasty‐balloon (PTCA‐balloon) was chosen (Figure 1).…”