| Part One The Impact of Cardiac Resynchronization Therapy on Echocardiography and Myocardial Perfusion1.1The Impact of Cardiac Resynchronization Therapy on Echocardiographic ParametersObjective:To investigate the impact of cardiac resynchronization therapy (CRT) on2-dimensional and3-dimensional echocardiography in ischemic cardiomyopathy.Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. Speckle tracking imaging was used to evaluate standard deviation of time to peak circumferential strain (Cirl2SD), radial strain (R12SD) and longitudinal strain (L12SD) of12segments of left ventricle. LVEF, LVEDV and LVESV were also measured by3-dimensional echocardiography.Results:There were no significant differences of LVEF, LVEDV, LVESV, Cir12SD, R12SD and L12SD between group A and group B at baseline and before CRT (p>0.05). After4weeks of CRT, it showed significant differences of LVEF, LVEDV, LVESV, Cir12SD and R12SD between the two groups (53.3±12.6%vs.39.2±6.9%,30.0±4.1ml vs.34.0±2.1ml,14.3±2.5ml vs.22.8±4.3ml,31.2±6.9ms vs.41.7±10.8ms and43.9±17.1ms vs.65.7±9.7ms, all p<0.05). However, L12SD showed no difference between group A and group B (55.4±9.7ms vs.55.9±15.0ms,p>0.05).Conclusions:CRT can improve systolic function and synchrony of left ventricle in ischemic cardiomyopathy. 1.2The Impact of Cardiac Resynchronization Therapy on Myocardial PerfusionObjective:To investigate the impact of cardiac resynchronization therapy (CRT) on myocardial perfusion in ischemic cardiomyopathy using myocardial contrast echocardiography (MCE).Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. MCE was used to evaluating the myocardial perfusion by measure A, β and myocardial blood flow (MBF) value at baseline, before CRT and after CRT.Results:There were no significant differences of A, β and MBF value between group A and group B at baseline (13.5±4.2dB vs.15.2±3.2dB,5.2±2.31/s vs.5.1±2.21/s,70.2±11.3dB/s vs.76.4±9.3dB/s,p>0.05). A, p and MBF value before CRT showed no significantly different between the two groups (7.2±2.8dB vs.7.7±1.7dB,3.3±1.61/s vs.3.0±1.91/s,25.9±5.9dB/s vs.23.6±5.7dB/s,p±0.05). After4weeks of CRT, A, β and MBF value in group A were improved significantly than those in group B (11.3±2.7dB vs.9.0±3.5dB,4.2±1.21/s vs.3.±1.81/s,49.8±15.5dB/s vs.28.5±4.6dB/s,p<0.05).Conclusions:CRT can improve myocardial perfusion, which can be quantified by A, β and MBF value using MCE in ischemic cardiomyopathy. Part Two The Predictive Parameters of Cardiac Resynchronization Therapy2.1The Predictive Value of Biochemical Parameters on Cardiac Resynchronization TherapyObjective:To investigate the predictive value of serum brain-type natriuretic peptide (BNP), C-reactive protein (CRP) and myeloperoxidase (MPO) levels in predicting the prognosis of cardiac resynchronization therapy (CRT) in ischemic cardiomyopathy.Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. After4weeks of CRT, group A was divided into group C (CRT response group) and group D (CRT non-response group). Serum BNP, CRP and MPO levels were tested at baseline,1hour after myocardial infarction,1day after myocardial infarction, before CRT,2weeks after CRT and4weeks after CRT.Results:There were no significant differences of serum BNP, CRP, and MPO levels at baseline,1hour after myocardial infarction,1day after myocardial infarction and before CRT between group B, group C and group D (p>0.05). At2weeks and4weeks after CRT, serum BNP, CRP, and MPO levels in group C were significantly lower than those in group B and group D (p<0.05). The AUC of BNP, CRP, and MPO before CRT was0.576,0.696, and0.596, respectively0>0.05).Conclusions:Serum BNP, CRP, and MPO levels in ischemic cardiomyopathy after CRT changed with therapy duration. CRT-response can lower the serum levels of BNP, CRP, and MPO. Serum BNP, CRP, and MPO levels before CRT showed no predictive value in predicting the response of CRT. 2.2The Predictive Value of Echocardiographic Parameters in the Response of Cardiac Resynchronization TherapyObjective:To investigate the predictive value of LVEDV, LVESV, Cirl2SD, R12SD, and L12SD in the response of cardiac resynchronization therapy (CRT) in ischemic cardiomyopathy.Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. After4weeks of CRT, group A was divided into group C (CRT response group) and group D (CRT non-response group). LVEDV, LVESV, Cirl2SD, R12SD, and L12SD were measured at baseline, before CRT, and4weeks after CRT.Results:There were no significant differences of LVEF, LVEDV, LVESV, Cirl2SD, R12SD, and L12SD at baseline (p>0.05). There showed significant differences of LVEF, LVEDV, and R12SD at4weeks after CRT (p<0.05), while there were no significant differences of LVESV, Cirl2SD, and L12SD between group C and group D0>0.05). There were no significant differences of LVEDV, Cirl2SD, R12SD, and L12SD before CRT, but it showed a significant difference of LVESV between group C and group D. The LVESV before CRT was related to the response of CRT (correlation coefficient equals to0.836, p=0.010). When LVESV>17.3ml was defined as a cut-off value before CRT, the sensitivity and specificity of LVESV in predicting the response of CRT are83.3%and100%, respectively.Conclusions:CRT can improve LVEF, LVEDV, LVESV, Cirl2SD, and R12SD in ischemic cardiomyopathy. LVEDV, Cirl2SD, R12SD, and L12SD can not predict the response to CRT in ischemic cardiomyopathy before CRT. The LVESV before CRT in ischemic cardiomyopathy shows the predictive value in predicting the response to CRT. 2.3The Value of Myocardial Contrast Echocardiography in Predicting the Response of Cardiac Resynchronization TherapyObjective:To investigate the value of A, β, and MBF in predicting the response of cardiac resynchronization therapy (CRT) in ischemic cardiomyopathy using myocardial contrast echocardiography (MCE).Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. After4weeks of CRT, group A was divided into group C (CRT response group) and group D (CRT non-response group). A, β, and MBF were measured using myocardial contrast echocardiography at baseline, before CRT, and4weeks after CRT.Results:There were no significant differences of LVEF, A, β, and MBF at baseline (p>0.05). There were significant differences of LVEF, A, and MBF at4weeks after CRT between group C and group D (p<0.05), while there was no significant difference of β between group C and group D (p>0.05). There were no significant differences of A and β before CRT between group C and group D, but it showed a significant difference of MBF between the two groups. The MBF before CRT was related to the response of CRT (correlation coefficient equals to0.814,p=0.001). When MBF>24.9dB/s was defined as a cut-off value before CRT, the sensitivity and specificity of MBF in predicting the response of CRT are83.3%and100%, respectively.Conclusions:CRT can improve A, β, and MBF in ischemic cardiomyopathy measured by MCE. A and β can not predict the response to CRT in ischemic cardiomyopathy before CRT. The MBF value is related to the response of CRT. The MBF value before CRT in ischemic cardiomyopathy is valuable in predicting the response to CRT. Part Three The Molecular Mechanism of Cardiac Resynchronization Therapy on Myocardial PerfusionObjective:To investigate the molecular mechanism of cardiac resynchronization therapy on the improvement of myocardial perfusion which was evaluated by myocardial contrast echocardiography (MCE).Methods:Twenty adult Beagles were divided into group A (CRT group) and group B (non-CRT group). All of them had heart failure after a ligature in the first diagonal branch. A left ventricular epicardial lead, a right atrium and a right ventricle leads together with the pacemaker were implanted. The pacing was started in group A after myocardial infarction, but was not started in group B. After4weeks of CRT, group A was divided into group C (CRT response group) and group D (CRT non-response group). Myocardial tissue was collected from the marginal area of myocardial infarction. The expression of TGF-β1, p-Smad2/3, and Smad2/3in group B, group C, and group D were investigated.Results:The TGF-(31, p-Smad2/3, and Smad2/3were expressed at a low level in normal myocardial tissues. There showed a significant elevation of the expression of TGF-β1, p-Smad2/3, and Smad2/3at the marginal area of myocardial infarction. The collagen fibers of the marginal area of myocardial infarction in group C were significant less than that in group B or group D, meanwhile the expression of TGF-β1, p-Smad2/3, and Smad2/3in group C were also lower than that in group B and group D (p<0.05).Conclusions:In the individuals of response to CRT, CRT can inhibit the expression of TGF-β1, p-Smad2/3, and Smad2/3and reduce the deposition of collagen fibers, which leads to the improvement of cardiac function and myocardial perfusion. |
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