Closed-chest animal model of chronic coronary artery stenosis. Assessment with magnetic resonance imaging

Abstract

To evaluate the consequences of chronic non-occlusive coronary artery (CA) stenosis on myocardial function, perfusion and viability, we developed a closed-chest, closed-pericardium pig model, using magnetic resonance imaging (MRI) as quantitative imaging tool. Pigs underwent a percutaneous copper-coated stent implantation in the left circumflex CA (n = 19) or sham operation (n = 5). To evaluate the occurrence of myocardial infarction, cardiac troponin I (cTnI) levels were repetitively measured. At week 6, CA stenosis severity was quantified with angiography and cine, first-pass and contrast-enhanced MRI were performed to evaluate cardiac function, perfusion and viability. In the stenting group, cTnI values significantly increased at day 3 and day 5 (P = 0.01), and normalized at day 12. At angiography, 13/19 stented pigs had a stenosis >75%. Mean degree of CA stenosis was 91 +/- 4%, range 83-98%. At contrast-enhanced MRI, mean infarct size was 7 +/- 6%, range 0.7-18.4%. Five of the 6 pigs with stenosis <75% had no infarction. Stented pigs showed significantly higher Left-ventricular volumes and normalized mass (P < 0.05), and lower ejection fraction (P = 0.03) than the sham pigs. Both wall thickening and myocardial perfusion were significantly lower in animals with at least one segment >50% infarct (23 +/- 8%; 0.05 +/- 0.01 a.u./s) and animals with only <50% infarct segments (29% +/- 12%; 0.07 +/- 0.02 a.u./s), than sham pigs (52 +/- 6%; 0.10 +/- 0.03 a.u./s) (P < 0.001; P < 0.05). This minimally-invasive animal model of chronic, non-occlusive CA stenosis, presenting a mixture of perfusion and functional impairment and a variable degree of myocardial necrosis, can be used as substitute to study chronic myocardial hypoperfusion.

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

“…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). 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).…”

“…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).…”

Cardiovascular imaging 2010 in the International Journal of Cardiovascular Imaging

“…A useful closed-chest animal model for chronic coronary artery stenosis was developed by Wu et al and assessed with CMR [38]. Insights into the effects from chronic myocardial hypoperfusion may be gained from this model.…”

The emerging role of magnetic resonance imaging and multidetector computed tomography in the diagnosis of dilated cardiomyopathy

“…As the myocardial substrate underlying the dysfunction in the setting of CAD is heterogeneous, including stunned, ischaemic, hibernating, necrotic and scarred myocardium, the goal of myocardial viability assessment is to determine the ischaemic substrate. It is important to emphasise that different ischaemic substrates can be present within the same coronary perfusion territory [73, 74]. Only the viable substrates may recover function following reperfusion.…”