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OBJECTIVE@#To investigate the mechanism by which dripping pills (STDP) improves coronary microcirculation disorder (CMD) and cardiac dysfunction in a porcine model of myocardial ischemia-reperfusion injury.@*METHODS@#Fourteen minipigs were randomly selected for interventional balloon occlusion of the middle left anterior descending branch to induce CMD, and another 7 pigs received sham operation. The pig models of CMD were randomized equally into the model group and STDP-treated group. All the animals were fed with common feed for 8 weeks, and in STDP-treated group, the pigs were given STDP at the daily dose of 3 mg/kg (mixed with feed) for 8 weeks. Before and at the 8th week after the operation, the pigs underwent coronary angiography and echocardiography to determine the vessel lumen diameter and TIMI frame count (CTFC). The pathologies of the myocardium and the microvessels were examined with HE staining at the 8th week. Western blotting was used to detect the expression of silencing information regulator (Sirt1), peroxidase proliferator-activated receptor-γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), extracellular signal-regulated kinase1/2 (ERKI/2), Toll-like receptor 4 (TLR4), and uncoupling protein 2 (UCP2) in myocardial tissue.@*RESULTS@#Before and at the 8th week after the operation, the diameter of the anterior descending vessel in the 3 groups did not differ significantly ( > 0.05). At the 8th week, the number of CTFC frames in the model group increased significantly compared with that in the sham-operated group, but was obviously lowered by treatment with STDP ( < 0.05). Myocardial ischemia-reperfusion injury significantly increased the interventricular septal thickness at end-diastole, left ventricular end-diastole dimension, end-diastole volume, interventricular septal thickness at end-systole and left ventricular mass at 8 weeks after the modeling ( < 0.05), but such changes were significantly alleviated by treatment with STDP (P < 0.05). STDP treatment markedly alleviated myocardial microvascular congestion, thrombosis and peripheral inflammatory cell infiltration induced by myocardial ischemia-reperfusion, but atrophy of the myocardial muscle fiber remained distinct. STDP obviously suppressed the down-regulation of Sirt1, PGC-1α, and PPARα and the up-regulation of ERK1/ 2, TLR4, and UCP2 in the myocardial tissues induced by myocardial ischemia-reperfusion injury.@*CONCLUSIONS@#STDP has anti-inflammatory effects and regulates energy metabolism in the myocardium through modulating Sirt1, PGC-1α, PPARα, ERKI/2, TLR4, and UCP2 to improve CMD and cardiac dysfunction after myocardial ischemia-reperfusion.
Subject(s)
Animals , Rats , Drugs, Chinese Herbal , Microcirculation , Myocardial Reperfusion Injury , Myocardium , Rats, Sprague-Dawley , SwineABSTRACT
Objective To study the effect and mechanism of down-regulating Silt2/Robo 1 signaling pathway on rabbit iliac artery after angioplasty restenosis. Methods The 30 male New Zealand white rabbits were divided randomly into 3 groups , namely the blank group , the control group , and the experimental group , 10 rabbits in each group. Hign-fat feeding , the rabbits were produced endothelial denudation of iliac artery stenosis model. Another 4 weeks of feeding , percutaneous balloon angioplasty was performed. Then R5 antibody was injected into the abdominal cavity. After 4 weeks of feeding ,angiography again. The results of angiography was analysied by image workstation. The concentrations of Slit2 and Robo1 was detected by ELISA. The iliac artery tissue examined by HE staining. Results The rabbit iliac artery after angioplasty restenosis animal model was set up successfully. Compared with the control group and the experimental group , the serum concentration of Slit2 and Robo1 were significantly higher (P < 0.01) than the blank group. But in the experimental group, the Slit2 and Robo1 serum concentrations were significantly lower than those in the control group (P < 0.05) after R5 antibody intervention. The area ratio stenosis and diameter stenosis rate of iliac artery were reduced that confirmed by angiography. Conclusion The expression of Slit2/Robo1 was significantly higher in the rabbit model of vascular restenosis. R5 antibody can effectively inhibit the expression of Slit2/Robo1. Down regulation of Slit2/Robo1 signaling pathway in the treatment of restenosis after angioplasty in rabbits.
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Objective To study the effect of cardiac resynchronization therapy (CRT) on the cardiac function and arrhythmias of patients with chronic heart failure and left ventricular systolic dyssynchrony. Methods Thirty-two cases of patients with chronic heart failure and left ventricular systolic dyssynchrony underwent CRT therapy. And LEVESV, LVEDV, LVEF, LVEDD, MRA, LAA, MRA/LAA were detected by echocardiography while the cardiac function was kept stable. Then the left ventricular systolic 12 segment peak time (Ts) was measurements by tissue doppler in all patients, the poor (Ts-maxD) and standard deviation (Ts-SD) were also calculated. The 24-hour ambulatory 12-lead ECG was took postoperation. All the patients were treated by anti-heart failure drugs after CRT pacemeker implantantion. All these indicators were assessed again at 12 weeks later. Results Compared with the previous CRT pacemaker implantation, LVEF, LV dp/dpsignificantly increased (P 0.05). Atrial premature beats and paroxysmal atrial tachycardia were significantly reduced in the preoperative CRT (P 0.05). Conclusion CRT resynchronization therapy can improve left ventricular systolic function, and reduce the MRA and Ts. The mechanism may be associated with the improvement of left ventricular synchrony, reducing mitral regurgitation, and reducing the occurrence of atrial arrhythmias.
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<p><b>OBJECTIVE</b>To assess the feasibility and safety of using the modified active fixation pacing leads model to pace the right ventricular outflow tract septum.</p><p><b>METHODS</b>A total of 136 patients undergoing artificial heart pacemaker implantation with active fixation pacing leads were randomized into two groups to receive conventional right ventricular outflow tract pacing (CRVOTP) or modified right ventricular outflow tract pacing (MRVOTP). The electrode lead wire core was modeled in a double-curved three-dimensional shape in CRVOTP group and in a J-shaped bend in MRVOTP group before fixation at the right ventricular outflow tract septum.</p><p><b>RESULTS</b>Right ventricular outflow tract septum pacing was achieved successfully in all the patients. None of patients experienced serious complications. No significant differences were found between the two groups in the number of times of electrode fixation, pacing thresholds, impedance, R wave height or QRS wave width during the operation, but MRVOTP was associated with a reduced time of X -ray exposure and operation (P<0.05) due to the convenience in electrode modeling and in passing the leads through the tricuspid annulus and the direct access to the right ventricular outflow tract septum. Postoperative follow-up of the patients showed no incidence of active fixation pacing lead dislocation and comparable pacing thresholds of the ventricular electrodes, impedance, R wave height and QRS wave width between the two groups.</p><p><b>CONCLUTIONS</b>Using the modified active fixation pacing leads model to pace the right ventricular outflow tract septum can reduce the time of X -ray exposure and operation with a low probability of lead damage.</p>