Establishment of an experimental angiographic slow coronary flow model by microsphere embolism in swines

Abstract

No-reflow or slow-flow post revascularization remains a challenge in interventional cardiology. The "no-reflow" phenomenon is largely induced by microemboli of atherosclerotic debris, spasm, microvascular damage, and thrombi generated by percutaneous coronary intervention (PCI) procedure [1]. Clinical studies revealed that patients exhibiting no-reflow following reperfusion therapy for acute myocardial infarction (AMI) were associated with worse prognosis compared to patients without no-flow [1,2]. Currently, the mechanism of no-reflow has been exclusively studied in animal models of coronary artery ligation/ reperfusion [5] and coronary microembolization (CME) [3][4][5] in canine or pig models, as well as in the rat coronary autologous coronary thrombotic microembolism model [6]. However, ischemia/reperfusion model in pig and canine only partly reflects pathological changes of no-reflow, since clinical "no-reflow" phenomenon is largely induced by microemboli [1] but not induced by coronary artery occlusion. Recently, Ma et al. reported that continuous injection of 120,000 42 μm microspheres into the left anterior descending (LAD) did not induce changes on coronary thrombolysis in myocardial infarction (TIMI) grade and TIMI 3 coronary flow was maintained immediately after microembolization and hemodynamic parameters remained stable before and after CME [7]. Till now, there is no large animal model presenting angiographic evidence of slow flow.In this study, we established an angiographic coronary slow flow model in pig by repeated coronary injection of small doses of 40 μm microspheres. Eight male domestic pigs (3 to 4 months old, 25 ± 2 kg) were used in this study. Aspirin (2-3 mg/kg/d) was mixed in the food 3 days prior to experimental studies. All animals received humane care and that study protocols comply with the institution's guidelines.Pigs were anesthetized by an intramuscular injection of ketamine (15 mg/kg) combining with atropine (1 mg) and then fixed in a supine position on the workstation, 3-5 ml 3% pentobarbital sodium solution was injected via ear marginal vein on demand to maintain the anesthesia state. Oxygen saturation (SO 2 ) was measured with pulse oximeter. Anticoagulation was induced with 200 IU/kg heparin sodium. The right femoral artery was dissected and a 6 F vascular sheath was placed for arterial access. After initial coronary angiography (CAG) using 6 F JR3.5 guiding catheter (Medtronic, Inc.), ventriculography and LV pressure measurements with 5 F Pigtail catheter (Cordis Inc.), a 2.6 F infusion microtubule catheter (Terumo Corporation) was then placed at the middle part of the LAD artery for microsphere injection, and 0.1 ml stock solution with 12,000 microspheres was diluted in 5 ml saline and injected for 20 s through the 2.6 F infusion microtubule catheter; this procedure was repeated, followed by 2 × 0.2 ml stock solution diluted into 5 ml saline with 24,000 microsphere injection, then 0.3 ml stock solution diluted into 5 ml saline with 36,000 microsphere injection (interval bet...

Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights

“…We previously established a coronary thrombotic microembolism model in rats [ 10 ]. A swine model with angiographic CSFP was newly established by repeat coronary injection of small doses of 40 μ m microspheres in our laboratory [ 11 ]. In the present study, we observed the pathological and angiographic evolution in this CSFP model.…”

Efficacy of Shexiang Tongxin Dropping Pills in a Swine Model of Coronary Slow Flow

“…The method of the establishment of the SF model was similar to that previously reported ( Hu et al, 2014 ; Bai et al, 2015 ). Briefly, pigs were fasted for 12 h before the operation and had free access to drinking water until 4 h prior to operation.…”

“…Preliminary small-scale clinical studies confirmed that STDP could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow ( Wang et al, 2019 ; Lu et al, 2020 ; Tian et al, 2020 ), but the underlying mechanism is not fully unclear. In this study, we observed the angiographic effects of STDP in a large animal (Bama pig) with a slow-flow model established in our laboratory ( Hu et al, 2014 ; Bai et al, 2015 ) and observed its impact on serum and myocardial biomarkers related to inflammatory and angiogenetic pathways. We aimed to observe the effects of STDP by observing the coronary angiographic, hemodynamic, serum biomarkers, HE staining, and immunohistochemical staining changes in a swine model of coronary slow flow (SF) and explore the potential mechanisms related to these effects post-STDP treatment.…”

A Novel Large Animal Model of Thrombogenic Coronary Microembolization

“…Our model is unique in inducing CME using autologous thrombus in the setting of preceding ischemia. The majority of the large animal studies of CME employed intracoronary injection of microspheres (4, 18, 20–22). While the microspheres have some advantages (easy handling and dosing), they are chemically inert and therefore not chemoattractant.…”