The representative porcine model for human cardiovascular disease

Abstract

To improve human health, scientific discoveries must be translated into practical applications. Inherent in the development of these technologies is the role of preclinical testing using animal models. Although significant insight into the molecular and cellular basis has come from small animal models, significant differences exist with regard to cardiovascular characteristics between these models and humans. Therefore, large animal models are essential to develop the discoveries from murine models into clinical therapies and interventions. This paper will provide an overview of the more frequently used large animal models, especially porcine models for preclinical studies.

Figure 1

Porcine (a and b). (a) Right coronary artery. (b) Left coronary system. Human (c and d). (c) Right coronary artery. (d) Left coronary system. Similar anatomy and coronary distribution is shown of the left anterior descending, left circumflex, and right coronary arteries.

Figure 2

Baseline coronary angiogram was obtained for assessment of anatomic information of the LAD (a). The LAD with the first large diagonal artery (white arrowhead) is delineated. Angiographic confirmation of complete occlusion in the midportions (b) of the LAD with a PTCA balloon catheter (white arrow). Adapted from [12].

Figure 3

This picture demonstrates the porcine heart (a) and cross-sectional slice (b). The dark area stained with Evans Blue indicates nonischemic territory, and the red area stained with TTC is the area at risk for ischemia (TTC-positive). In (b), the white area is the infarcted (necrotic) myocardium (TTC-negative). The schema explains what the stained colors and territories indicate (c). LAD: left anterior descending artery. Adapted from [12].

Figure 4

(a) Photomicrographic section shows gross neointimal proliferation causing a significant stenosis (Hematoxylin-Eosin stain, x5). (b) In this section, the porcine coronary was totally occluded with neointimal hyperplasia. L: lumen; M: media; NI: neointima; ∗: stent strut. Adapted from the reference [32].

Figure 5

(a) X-rays of longitudinally cut rabbit iliac arteries at 21 days after placement of overlapping ZES, SES, and PES. The extent of stent coverage by endothelial cells was greatest with ZES, with almost complete coverage in the proximal and distal segments and significantly greater coverage in the overlapped segment compared with SES and PES. (b) Photomicrographs showing the amount of neointimal thickness at 28 days after placement of Endeavor zotarolimus-eluting stents (ZESs), Cypher sirolimus-eluting stents (SESs), Taxus paclitaxel-eluting stents (PESs), and Driver bare metal stents (BMSs) in rabbit iliac arteries. With SES, there were focally uncovered stent struts, which were associated with inflammation consisting of heterophils or eosinophils and giant cells. Adapted from [49].

Figure 6

Time course of coronary artery treated with thermal balloon. A severe tandem coronary artery stenosis is observed in the left anterior descending artery (LAD) at 4 weeks after thermal balloon injury [50].

Figure 7

Histological examinations of pig experiments. Elastic-van Gieson (a, b) and Von kossa (c, d) stained CTO segment of coronary arteries. Arrows in (c) and (d) indicate microcalcification. Ex vivo micro-CT confirms that CTO lesions contain calcification in LAD (red circle) [51].