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

Bai, Yusong; Hu, Liqun; Yu, Dian; Peng, Sheng; Liu, Xiaogang; Zhang, Mingjing; Gu, Ye

doi:10.1155/2015/623986

Cited by 5 publications

(9 citation statements)

References 21 publications

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“…Frangogiannis [80] classified the healing process of myocardial infarct into 3 distinct but overlapping phases: the inflammatory phase, the proliferative phase, and the maturation phase, while Nahrendorf et al [81] summarized the roles of monocytes/macrophages in infarct healing, including 1) release inflammatory mediators; 2) release proteases; 3) phagocytose apoptotic and necrotic myocytes and neutrophils and other debris; 4) promote angiogenesis; 5) transport reparative enzymes and prosurvival factors; and 6) stimulate collagen synthesis and deposition by myofibroblasts. It has been shown that multiple injections of microspheres also induce myocardial injuries similar to those seen in patients after revascularization [77]. Figure 8 shows the patchy microinfarct and infiltration of inflammatory cells in infarcted myocardium 3 days after microembolization.…”

Section: Histopathologymentioning

confidence: 74%

“…The animals showed complete recoveries of flow reserve and LV ejection fraction, but LV dilation, 1 week later [66]. Bai et al [77] also reported a persistent LV dysfunction and progressive remodeling in swine model 28 days after repeated microsphere injection.…”

Section: Myocardial Perfusionmentioning

confidence: 87%

“…Three days after delivery of solely emboli, necrotic myocytes were replaced with aggregates of mononuclear cells (mostly macrophages) [34]. Bai et al [77] observed an early increased inflammatory activity followed by persistent pro-inflammatory cytokines protein expression and collagen deposition. The use of iron particles, as MR contrast medium, might be helpful in noninvasively identifying and quantifying temporal changes in myocardial inflammation [82].…”

Section: Histopathologymentioning

confidence: 99%

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Coronary Embolization and Myocardial Microinfarction: MR Imaging and Histopathologic Characterization

Saeed¹,

Hetts²,

Liang³

et al. 2016

IJCM

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Magnetic resonance imaging (MRI) has been proven to reliably assess regional perfusion and left ventricular (LV) function of microembolized myocardium. The visibility of microinfarct on delayed enhancement MRI (DE-MRI) is limited and dependent on technical and biological issues. Furthermore, MRI underestimates total microinfarct size compared with microscopy. MRI studies revealed that the presence of microemboli in pre-existing acute infarct delays infarct healing and magnifies LV remodeling. Discrimination of acute from chronic microinfarct is based on presence of inflammatory cells, edema and scar tissue, respectively. These noninvasive findings highlight the importance of prognostic utility of MRI and warrant larger clinical studies or registries to evaluate the significance of presence of focal microinfarct. Serial microscopic studies revealed that intravascular microemboli migrate into the extravascular space and this migration process is a function of time. This phenomenon may limit the use of microemboli therapy in occluding hemorrhagic blood vessels or treating tumors. Despite current standard of care, existing methods and therapies do not prevent coronary embolization nor reverse their deleterious effects.

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Section: Histopathologymentioning

confidence: 74%

Section: Myocardial Perfusionmentioning

confidence: 87%

Section: Histopathologymentioning

confidence: 99%

See 1 more Smart Citation

Coronary Embolization and Myocardial Microinfarction: MR Imaging and Histopathologic Characterization

Saeed¹,

Hetts²,

Liang³

et al. 2016

IJCM

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show abstract

“…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.…”

Section: Discussionmentioning

confidence: 99%

A Novel Large Animal Model of Thrombogenic Coronary Microembolization

Bikou

Tharakan

Yamada

et al. 2019

Front. Cardiovasc. Med.

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Coronary microembolization is one of the main causes of the “no-reflow” phenomenon, which commonly occurs after reperfusion of an occluded coronary artery. Given its high incidence and the fact that it has been proven to be an independent predictor of cardiac morbidity and mortality, there is an imperative need to study its underlying mechanisms and pathophysiology. Large animal models are essential to perform translational studies. Currently there is no animal model that recapitulates a clinical scenario of thrombogenic microembolism with preceding myocardial ischemia. Therefore, the goal of this study was to develop and characterize a novel pig model of coronary microembolization using autologous thrombus injection (CMET). Twenty-three pigs underwent myocardial infarction through percutaneous balloon occlusion of the left anterior descending artery (LAD). Each animal was enrolled in one of two groups: (1) the CMET group, in which the LAD occlusion was followed by delivery of autologous clotted blood in the LAD (distal to the balloon occlusion) and reperfusion; (2) the ischemic reperfusion (I/R) group, in which the LAD ischemia was followed by reperfusion. Surviving animals underwent functional and morphological characterization at 1-week post-procedure. Three sham operated animals were used as a control. CMET resulted in impaired left ventricular function compared to I/R pigs at 1 week. Three-dimensional echocardiography demonstrated reduced ejection fraction in the CMET group (CMET vs. I/R: 35.6 ± 4.2% vs. 47.6 ± 2.4%, p = 0.028). Invasive hemodynamic measurements by Swan-Ganz and left ventricular pressure-volume catheters revealed that CMET impaired left ventricular contractility and diastolic function. This was confirmed by both load-dependent indices including cardiac output (CMET vs. I/R: 2.7 ± 0.2 l/min, vs. 4.0 ± 0.1 l/min, p = 0.002) and load independent indices including preload-recruitable stroke work (CMET vs. I/R: 25.8 ± 4.0 vs. 47.5 ± 6.5 mmHg, p = 0.05) and end-diastolic pressure-volume relationship (slope, 0.68 ± 0.07 vs. 0.40 ± 0.11 mmHg/ml, p = 0.01). Our unique closed-chest model of coronary microembolization using autologous thrombus injection resembles the clinical condition of thrombogenic coronary microembolization in I/R injury. This model offers opportunities to conduct translational studies for understanding and treating coronary microembolization in myocardial infarction.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms.Methods: SF was induced by coronary injection of 40μm microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting.Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group.Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression.

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

Cited by 5 publications

References 21 publications

Coronary Embolization and Myocardial Microinfarction: MR Imaging and Histopathologic Characterization

Coronary Embolization and Myocardial Microinfarction: MR Imaging and Histopathologic Characterization

A Novel Large Animal Model of Thrombogenic Coronary Microembolization

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

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