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Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.
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OBJECTIVE@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.@*METHODS@#Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg@*RESULTS@#The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).@*CONCLUSION@#STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.
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Objective To investigate the effect of diallyltrisulfide on rats with myocardial injury after coro-nary microembolization (CME). Methods 20 survival of SD rats were randomly divided into CME group (CME group)and diallyltrisulfide pretreatment group(DATSgroup),and these rats were injected with microspheres(42 μm in diameter)into the left ventricles to induce the model of CME, 10 rats for each group.DATS group was received diallyltrisulfide (DATS) 40 mg/(kg·d) for 7 days before operation. Another 10 survival of SD rats was selected as sham operation group(Sham group),and these rats were injected with the same dose of normal saline by left ventri-cles. Cardiac function was assessed by echocardiography and the expression of Akt and caspase-3 of myocardial tissue of rats in each group were detected by TUMEL staining,RT-PCR and Western Blot,while testing the level of cTnI after operation of 6 h. Results Compared with Sham group, the cardiac function of CME group and DATS group was significantly decreased (P<0.05), the expression of caspase3 mRNA and protein was significantly increased (P<0.05), the expression on Akt mRNA and protein was significantly decreased (P<0.05) (P<0.05). Com-pared with CME group, the cardiac function of DATS group was significantly improved (P<0.05), the expression of caspase3 mRNA and protein was significantly decreased (P<0.05), the expression of Akt mRNA and protein was significantly increased (P<0.05), cTnI level was significantly decreased (P<0.05). Conclusion Diallyltrisulfide pretreatment can significantly reduce the apoptosis of cardiomyocytes after CME and improve cardiac function.The mechanism may be through the inhibition of Akt to activate cardiomyocyte caspase3-mediated death receptor activa-tion pathway.
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Objective To investigate the role of TLR4/NF-κB signaling pathway under the action of TAK-242 in the cardiomyocyte apoptosis after coronary micro-embolism (CME) in rats.Methods Fortyfive rats were randomized (random number) into three groups:sham operation,CME and CME plus TAK242 groups (n =15 per group).CME was induced by injecting polyethylene microspheres (42 μm) into the left ventricle except the sham group.CME plus TAK-242 group was treated with TAK-242 (2 mg/kg) via the tail vein of mice 30 min before CME modeling.Cardiac function was evaluated 6 h after operation.Tissue biopsy was stained with HBFP to measure the size of infarction area.TUNEL assay was used to detect cardiomyocyte apoptosis.Western blot and qPCR were used to evaluate the protein levels and mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3,respectively.Statistical analysis was performed using one-way analysis of variance followed by LSD-t test.Results Compared with the sham group,left ventricular ejection fraction (LVEF) in the CME group was significantly decreased [(68.91 ± 4.12) ％ vs.(84.80 ± 2.51) ％,P ＜ 0.05],and the infarction area (P ＜ 0.05),the apoptosis index [(3.36 ± 0.63) ％ vs.(0.19 ± 0.08) ％,P ＜0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME group were increased significantly (all P ＜ 0.05).Compared with CME group,LVEF in the CME plus TAK-242 group was significantly improved [(75.58 ± 5.01) ％ vs.(68.91 ± 4.12) ％,P＜0.05],and the infarction area [(8.58 ± 2.12) ％ vs.(14.65 ± 4.23) ％,P＜0.05],the apoptosis index [(1.43 ± 0.51) ％ vs.(3.36 ± 0.63) ％,P ＜ 0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME + TAK-242 group were decreased significantly (all P ＜ 0.05).Conclusions TAK-242 effectively improved CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the cardiomyocyte apoptosis.
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Objective To assess the MR characterization of coronary microembolization (CME)in an animal model as well as the evolution using MR cardiac cine,first-pass perfusion,and delay enhancement imaging.Methods Coronary microembolization models were established through intracoronary infusion of 120 000 microspheres (42 μm)into the left anterior descending artery in 1 1 pigs. Coronary angiography was performed at baseline and immediately after the injection of microspheres.MR imaging was carried out at baseline,6 hours,and 1 week after microembolization.Then,postmortem evaluation was performed using NBT and HE staining.Re-sults Coronary angiography after the injection of microspheres showed normal-appearing epicardial arteries in all animals.Coronary microembolization caused a significant decline in systolic wall thickening of the microembolized myocardial segments on cine MR ima-ges [from (42.6±2.0)% at baseline to (20.3±2.3)% at 6 hours and (31.5±2.1)% at 1 week after CME;P < 0.001 for both]. First-pass perfusion deficit was visualized at 6 hours after microembolization,and was less pronounced at 1 week.Hyperenhanced myocardium was found on delay enhancement MRI at 6 hours after microembolization in microembolized segments,but was not shown at 1 week. The microinfarcts were detectable microscopically through HE staining but invisible for the naked eye on gross NBT specimen.Con-clusion Coronary microembolization may cause a persistent decline in myocardial contraction and its MR characterization may vary with different stages.A combined use of different cardiac MRI techniques and follow-up examinations may be helpful for evaluating myocardial impairment due to coronary microembolization.
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We report a 90-year-old man with intestinal necrosis of the sigmoid colon after EVAR. His abdominal aortic aneurysm was 7.3 cm in diameter, and mural thrombus was present from the abdominal aortic aneurysm to the proximal common iliac arteries. Because type Ib endoleakage from the right distal edge of the stent graft was present, extension to the iliac bifurcation was performed using an additional leg device. The external iliac artery was severely calcified and tortuous ; thus, insertion of the leg device was technically difficult. Immediately after the operation, abdominal distention, right trash foot, and a small amount of rectal bleeding were observed. The patient was managed conservatively, and the symptoms resolved within a few days. Oral intake was started on postoperative day 5. However, 4 days after the initiation of oral intake, the patient suffered from abdominal pain and fever. Free air was observed by chest X-ray and computed tomography. Emergency laparoscopic examination revealed intestinal necrosis and perforation of the sigmoid colon. Therefore, the sigmoid colon was resected, and a transverse colostomy was performed. The patient recovered relatively well, with oral food intake beginning on day 6 and rehabilitation on day 8. He was discharged in good condition with unaided ambulation 5 weeks after bowel resection. Pathological examination demonstrated ischemic colitis due to cholesterol emboli.
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Objective To develop miniature pig model of coronary microembolization (CME) by easy and cost-effi-cient technique. Methods A total of 11 miniature pigs were divided into control group (n=5) and CME group (n=6). Femo-ral artery was punctured using 21 gauge needle that is normally used for transradial procedures. Microspheres were injected into the left anterior descending artery of the CME group by 5 F coronary radiography catheter and 1.8 F coronary micro-guide catheter. Serum concentrations of brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were evaluated just be-fore CME and 6 hours after CME. Apical myocardial pathological lesions were evaluated by optical microscope 6 hours after CME. Results All miniature pigs in control group survived, but one died in the CME group. 5 F coronary radiography cathe-ter and 1.8 F coronary micro-guide catheter reached designated location successfully. Before CME, serum BNP (ng/L:143.00 ± 13.51 vs 134.00 ± 15.57) and cTnI (μg/L:0.39 ± 0.09 vs 0.38 ± 0.10) showed no significant differences between these two groups (t values are 0.976 and 0.294 respectively,both P>0.05). By contrast, serum BNP (561.00 ± 80.65) and cTnI (2.75±0.58) were much higher in CME group than those (BNP 139.00±13.87;cTnI 0.54±0.14 ) in control group after CME (t values are 11.530 and 8.337 respectively,both P＜0.001). In CME group, microspheres, micro-infarction and inflammatory cell infiltration were seen under an optical microscope which are absent in control group. Conclusion Using new surgical consumables can successfully develop miniature pig model with CME. And the technique is simple, cost-efficient, practical so it is worth promoting.
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@#BACKGROUND: Coronary microembolization (CME) is a serious complication following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The use of metoprolol before PCI can significantly protect ischemic myocardium from myocardial damage, but the function of metoprolol in the treatment of CME is not entirely clear. This study was to explore the effect and significance of metoprolol on myocardial apoptosis and caspase-3 activation after CME in rats. METHODS: Thirty rats were randomly divided into three groups including sham-operation (control group), CME plus saline (CME group), CME plus metoprolol (metoprolol group), 10 rats for each group. The CME group was induced by injecting 3000 polyethylene microspheres (42 μm) into the left ventricle during a 10-second occlusion of the ascending aorta; the control group was injected with physiological saline instead of microembolization ball; the metoprolol or saline group was given three intravenous bolus injections before CME. Echocardiography, TUNEL staining, and Western blotting were used to evaluate cardiac function, proportion of apoptotic cells and activation of caspase-3 respectively at 6 hours after operation. RESULTS: Echocardiographic parameters displayed that the metoprolol group improved cardiac function significantly compared with the CME group (P<0.05). The myocardial apoptotic rate of the CME group as wel as the contents of activated caspase-3 increased significantly (P<0.05), both of which were ameliorated significantly by metoprolol treatment (P<0.05). CONCLUSIONS: This study demonstrates that metoprolol can protect the myocardium during CME in rats by inhibiting apoptosis and improving cardiac function. These results suggest that the inhibition of apoptosis can be a potential therapeutic strategy for the treatment of CME.
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Objective To investigate the expression of inflammatory factors in myocardium following coronary microembolization (CME) and effect of NF-kB inhibitor on the expression. Methods CME models were created in 64 rats by injecting homologous microthrombotic particle suspension into the left ventricle with the ascending aorta clamped. The model rats were equally divided into untreated group and pyrrolidine dithiocarbamate (PDTC) treatment group; the animals were sacrificed at 1, 3, 7, and 14 days after operation. Another 24 SD rats served as sham controls. The distribution and dynamic changes of TNF-α, IL-6 and ICAM-1 mRNA expressionin myocardium were determined by in situ hybridization and immunohistochemistry. Results CME associated inflammation was not limited to the surroundings of the microembolization; it also involved a great deal of "innocent" myocardium, producing bystander effect. Myocardium expression of TNF-α, IL-6, and ICAM-1 in CME group was significantly higher than that in the sham control group (P<0.05). NF-kB inhibitor PDTC significantly inhibited TNF-α, IL-6 and ICAM-1 expression after CME (P<0.05). Conclusion CME can produce amplified myocardial inflammation, and NF-kB inhibitor PDTC can markedly ameliorate myocardial inflammation.
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Objective To investigate the dynamic changes of cardiomyocyte apoptosis and Caspase-12 activation after coronary microembolization (CME) in rats. Methods The CME models were produced by injection of 42 μm microspheres (3000/0.1 ml) into the left ventricle during clampinduced ascending aorta occlusion for 10 seconds in adult male Sprague-Dawley rats (CME group).The sham-operation group was injected with saline instead (S group). The survivors were randomly divided into five groups: 3 h, 6 h, 12 h, 24 h and 4 weeks (n=10, each), respectively. In addition,10 rats were designed as normal control group. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The expressions of Caspase-3, 12 and procaspase-3 and 12 were detected with Western-blot analysis. The activity of Caspase-12 was determined with fluorometric assay kit. Results (1)Compared with the shamoperation group and normal control group, the apoptosis rates of cardiomyocytes in CME group were significantly increased at each time point respectively (all P＜0.05). Apoptotic cardiomyocytes were found mainly in the border zones and infarct foci. The apoptosis rates of cardiomyocytes at 3 h, 6 h,12 h, 24 h and 4 weeks after CME were (1.76±0.68)%, (3.17±1.26)%, (1.34±0.12)%,(1.07±0.65)% and (0.30±0.13)%, respectively. The apoptosis rates of cardiomyocytes increased at 3 h after CME, peaked at 6 h after CME (all P＜0.05), and then gradually decreased with lowest value at 4 weeks (all P＜0.01). (2)Compared with sham-operation group and normal control group,the relative activation level of Caspase-3 and 12 in CME group increased remarkably (all P＜0.05).The time courses of Caspase-3 and 12 expressions corresponded well to those of cardiomyocyte apoptosis after CME. Conclusions The amount of cardiomyocytes apoptosis is significantly increased after CME. Caspase-12 may be involved in the apoptosis of cardiomyocyte after CME.
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Objective By using percutaneous endovascular microcatheter technique to establish an animal model of coronary microembolization in mini-swine which is suitable for long-term observation.Methods Coronary microembolization was established in 10 mini-swine by infusing 15 × 10~4 microspheres (φ45μm) selectively into the left anterior descending artery (n = 10). Coronary flow reserve (CFR) was measured by Doppler wire and left ventricular eject fraction (EF) was assessed by echocardiography.Hematoxylin and eosin (HE) staining and nitroblue tetrazolium (NBT) dye were used to demonstrate the presence of microembolization after the procedure of coronary microembolization. The ultra-structures of cardiomyocyte were observed by transmission electron microscopy (TEM). Before sacrifice, the CFR measurement and coronary angiography were performed again in survival animals. Results The coronary microvascular integrity (CFR < 2.0) and left ventricular function (EF < 50% ) were damaged by coronary microembolization. One month after the procedure, all the 10 animals survived and were able to receive the angiography and CFR measurement again. HE staining and NBT dye could demonstrate the presence of microembolization. The edema and fibrosis of cardiomyocytes could be revealed with TEM. Conclusion The animal model of coronary microembolization can be established in mini-swine by using percutaneous endovascular microcatheter technique. The model is suitable for long-term observation, the preparation is technically-simple and minimally-invasive with very low mortality. Therefore, this kind of animal model is an ideal experimental form for studying the mechanism of coronary microembolization.
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We recently obsesved an unusual case of visual loss after the facial injection of autologous fat. A 42-year-old woman underwent autologous fat injection into the temple area to reduce facial wrinkles. The procedure was performed by a surgeon at local clinic. The patient immediately complained of severe right hemicranial pain and lid swelling. She vistied to the ophthalmic department of our hospital 1 week later because of total loss of vision on the right eye. We believe that the cause of blindness was multiple microembolization in the central retinal artery and posterior ciliary branches of the ophthalmic artery via lateral palpebral artery.