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Percutaneous microembolization of the left coronary artery to model ischemic heart disease in rats

Lab Animal volume 45, pages 20–27 (2016)Cite this article

Abstract

Small animal models of myocardial infarction are used for a wide variety of research purposes, but common techniques for generating such models require thoracic surgeries that increase mortality risk and damage important structures, such as the pericardial sac. Here, we describe a technique for modeling myocardial infarction in rats by selective coronary microembolization, which has hitherto been described only in large animals. This technique selectively catheterizes the left coronary artery using a custom-made catheter that is introduced and precisely placed under fluoroscopic guidance. Microspheres are then injected through the catheter to cause embolization. This process creates multiple simultaneous micro-infarcts that resemble those from clinical embolization after a percutaneous coronary intervention. As this technique does not require thoracic surgery, a low attrition rate was expected and once it was optimized, this technique had a low mortality rate of just 14% during experimental application. This technique creates infarcts that appear small but are associated with transient ECG changes and a persistently lower ejection fraction after embolization. Microspheres are retained in the myocardial tissue and are visible by epifluorescent microscopy after histological staining and recognizable as a distinct speckle pattern in ultrasound images.

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Figure 1: Diagram illustrating the customized end of our polyethylene catheter, including 90° bend and 3.8 mm tip.
Figure 2: In vivo angiograms of the left coronary artery of a rat, with features delineated by contrast medium and recorded by fluoroscopy.
Figure 3: ECG recording for lead I on a rat during the catheterization procedure.
Figure 4: Timeline for treatments and assessments during the experiment, including preoperative assessments (pre-op), baseline measurements taken at the start of surgery (base), measurements taken at the time of embolization (embo) and postoperative measurements taken 30 min, 3 d and 7 d or 28 d after embolization.
Figure 5: Ultrasound images of a rat's heart using the short axis view.
Figure 6: ECG recordings (mean ± s.e.m.) for rats measured during the preoperative assessment (pre-op; n = 14), the start of surgery (base), embolization (embo), 30 min after embolization and during postoperative assessments at 3 d (n = 12), 7 d (n = 6) and 28 d (n = 6) after embolization.
Figure 7: Ventricular function, as measured from ultrasound images (mean ± s.e.m.) declined mildly after embolization, and (a) ejection fraction and (b) fractional shortening were both significantly smaller at 7 d after embolization than they were during the preoperative assessment.
Figure 8: Transverse sections of a rat's intact heart after embolization, (a) under normal light and (b) under ultraviolet light.
Figure 9: Four sections of heart tissue stained using Masson's trichrome stain for histological analysis, from rats 28 days after embolization.

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Authors and Affiliations

  1. Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, Maastricht, 6629 ER, The Netherlands

    Allard Wagenaar,  Rob F. Wiegerinck,  Viviane V. T. Heijnen &  Mark J. Post

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  1. Allard Wagenaar
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  2. Rob F. Wiegerinck
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  3. Viviane V. T. Heijnen
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  4. Mark J. Post
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Correspondence to Mark J. Post.

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Wagenaar, A., Wiegerinck, R., Heijnen, V. et al. Percutaneous microembolization of the left coronary artery to model ischemic heart disease in rats. Lab Anim 45, 20–27 (2016). https://doi.org/10.1038/laban.909

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