Objective To evaluate the effects of BQ-123 on cardiac function and ventricular remodelling after coronary microembolization (CME) in rats. Methods We created a rat model of CME by injecting a suspension of autogenic ...Objective To evaluate the effects of BQ-123 on cardiac function and ventricular remodelling after coronary microembolization (CME) in rats. Methods We created a rat model of CME by injecting a suspension of autogenic microthrombotic particles into left ventricle. Three days after the procedure, the 30 surviving rats were randomly divided into 3 groups, each consisted of 10 rats: sham-operation group(SO), CME model group(CM) and BQ-123 intervention group(BQ). Rats in the BQ group received BQ-123 (400μg/kg per day, intraperitoneally) for 4 weeks. Plasma and myocardial endothelin-1 (ET-1) were measured by radioimmunoassay. And serial echocardiography was performed to monitor alterations of left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening(LVFS) and ejection fraction (LVEF), and physiologicography to document the changes of left ventricular systolic pressure (LVSP) and end-diastolic pressure pressure(LVEDP), and left ventricular maximum positive and negative dp/dt (±LVdp/dtmax). Results Compared with sham-operated group, both LVEDD and LVESD were increased (P【0.01), whereas LVFS and LVEF were significantly decreased (P【0.01) in CME group; LVEDP was markedly increased, while LVSP and±LVdp/ dtmax markedly reduced in CME group (P【0.01); plasma and tissue ET-1 levels increased in CME group (P【0.01). BQ-123 intervention significantly decreased both the plasma and tissue ET-1 levels (P【0.01), and markedly increased LVFS and LVEF, with significant improvement of LVSP and±LVdp/ dtmax (P【0.01). Conclusions Treatment with BQ-123 prevents ventricular remodeling after CME due to suppression of the endothelin system.展开更多
Objectives To explore changes of myocardial pro-inflammatory and fibrogenic cytokines after coronary microembolization (CME) in rats. To observe effects of carvedilol at different doses on myocardial cytokines express...Objectives To explore changes of myocardial pro-inflammatory and fibrogenic cytokines after coronary microembolization (CME) in rats. To observe effects of carvedilol at different doses on myocardial cytokines expression and ventricular remodeling. Methods A rat model of CME was created by injecting a suspension of microthrombotic particles generated from rat clots into left ventricle when clamping the ascending aorta. Forty SD rats were randomly divided into 4 groups(n=10 per group): sham-operation group(SO), CME group(ME), low-dose carvedilol intervention group (LCAR,1.0 mg·kg-1·d-1) and high-dose carvedilol intervention group (HCAR, 10.0 mg·kg-1·d-1). A microscopy incorporated with an image analysis software was employed to calculate the number of micro-myocardial infarction (Nmmi) and the area of micro-myocardial infarction (Ammi) in sections with HE-staining, to measure the collagen volume fraction(CVF) in sections with Sirius-Red-staining, to detect the density of expressions of TNF-α, IL-1β, TGF-β1 and MMP-9 in sections with immunohistchemical staining, to calculate the myocyte apoptosis rate (Rapo) in sections with TUNEL-staining. Two-dimensional Echocardiography was performed to monitor left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), left ventricular fraction shortening (LVFS) and ejection fraction (LVEF); and electrophysiolography was utilized to measure left ventricular systolic pressure(LVSP), maximal positive dp/dt (+ LVdp/dtmax), and end diastolic pressure(LVEDP). Four weeks after operation, comparing measurements in ME with those in SO, both Nmmi and Ammi were increased(P【0.01, each); all of the expressions of TNF-α, IL-1β, TGF-β1 and MMP-9 were increased (P【0.01,each), both CVF and Rapo were increased (P【0.01,each), both LVEDD and LVESD were increased but LVFS and LVEF were reduced(P【0.01,each), both LVSP and+ LVdp/dtmax were increased (P【0.01,each), but LVEDP was increased (P【0.01). Comparing with measurements in ME, the expression of TNF-α, IL-1β, TGF-β1 and MMP-9 were decreased(P【0.01,each), both CVF and Rapo were decreased(P【0.01,each), LVEDD and LVESD were smaller(P【0.01,each), LVEF and LVFS was higher(P【0.01,each), +LVdp/ dtmax were increased and LVEDP was decreased(P【0.01,each), heart rate were slower (P【0.01,each) both in LCAR and HCAR. Except for LVSP, the above-mentioned changes were more remarkable in HCAR than in LCAR(P【0.05). Myocyte interstitial CVF was positively correlated with the expression of IL-ip and TGF-β1(r=0.81 and 0.93, P【0.01), the activity of MMP-9 was obviously positively correlated with the expression of TNF-αand IL-β1(r=0.90 and 0.91, P 【0.01), and Rapo was positively correlated with the expression of TNF-α(r=0.88, P【0.01). Conclusions Left ventricle is undergoing progressive remodeling after CME due to abnormal expressions of pro-inflammatory and fibrogenic cytokines leading to myocyte apoptosis and interstitial collagen proliferation. Via down-regulating the expressions of these cytokines, Carvedilol intervention decreases myocyte apoptosis, interstitial collagen proliferation and improve ventricular function.展开更多
文摘Objective To evaluate the effects of BQ-123 on cardiac function and ventricular remodelling after coronary microembolization (CME) in rats. Methods We created a rat model of CME by injecting a suspension of autogenic microthrombotic particles into left ventricle. Three days after the procedure, the 30 surviving rats were randomly divided into 3 groups, each consisted of 10 rats: sham-operation group(SO), CME model group(CM) and BQ-123 intervention group(BQ). Rats in the BQ group received BQ-123 (400μg/kg per day, intraperitoneally) for 4 weeks. Plasma and myocardial endothelin-1 (ET-1) were measured by radioimmunoassay. And serial echocardiography was performed to monitor alterations of left ventricular end-systolic and end-diastolic diameter (LVESD, LVEED), and left ventricular short-axis fraction shortening(LVFS) and ejection fraction (LVEF), and physiologicography to document the changes of left ventricular systolic pressure (LVSP) and end-diastolic pressure pressure(LVEDP), and left ventricular maximum positive and negative dp/dt (±LVdp/dtmax). Results Compared with sham-operated group, both LVEDD and LVESD were increased (P【0.01), whereas LVFS and LVEF were significantly decreased (P【0.01) in CME group; LVEDP was markedly increased, while LVSP and±LVdp/ dtmax markedly reduced in CME group (P【0.01); plasma and tissue ET-1 levels increased in CME group (P【0.01). BQ-123 intervention significantly decreased both the plasma and tissue ET-1 levels (P【0.01), and markedly increased LVFS and LVEF, with significant improvement of LVSP and±LVdp/ dtmax (P【0.01). Conclusions Treatment with BQ-123 prevents ventricular remodeling after CME due to suppression of the endothelin system.
文摘Objectives To explore changes of myocardial pro-inflammatory and fibrogenic cytokines after coronary microembolization (CME) in rats. To observe effects of carvedilol at different doses on myocardial cytokines expression and ventricular remodeling. Methods A rat model of CME was created by injecting a suspension of microthrombotic particles generated from rat clots into left ventricle when clamping the ascending aorta. Forty SD rats were randomly divided into 4 groups(n=10 per group): sham-operation group(SO), CME group(ME), low-dose carvedilol intervention group (LCAR,1.0 mg·kg-1·d-1) and high-dose carvedilol intervention group (HCAR, 10.0 mg·kg-1·d-1). A microscopy incorporated with an image analysis software was employed to calculate the number of micro-myocardial infarction (Nmmi) and the area of micro-myocardial infarction (Ammi) in sections with HE-staining, to measure the collagen volume fraction(CVF) in sections with Sirius-Red-staining, to detect the density of expressions of TNF-α, IL-1β, TGF-β1 and MMP-9 in sections with immunohistchemical staining, to calculate the myocyte apoptosis rate (Rapo) in sections with TUNEL-staining. Two-dimensional Echocardiography was performed to monitor left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), left ventricular fraction shortening (LVFS) and ejection fraction (LVEF); and electrophysiolography was utilized to measure left ventricular systolic pressure(LVSP), maximal positive dp/dt (+ LVdp/dtmax), and end diastolic pressure(LVEDP). Four weeks after operation, comparing measurements in ME with those in SO, both Nmmi and Ammi were increased(P【0.01, each); all of the expressions of TNF-α, IL-1β, TGF-β1 and MMP-9 were increased (P【0.01,each), both CVF and Rapo were increased (P【0.01,each), both LVEDD and LVESD were increased but LVFS and LVEF were reduced(P【0.01,each), both LVSP and+ LVdp/dtmax were increased (P【0.01,each), but LVEDP was increased (P【0.01). Comparing with measurements in ME, the expression of TNF-α, IL-1β, TGF-β1 and MMP-9 were decreased(P【0.01,each), both CVF and Rapo were decreased(P【0.01,each), LVEDD and LVESD were smaller(P【0.01,each), LVEF and LVFS was higher(P【0.01,each), +LVdp/ dtmax were increased and LVEDP was decreased(P【0.01,each), heart rate were slower (P【0.01,each) both in LCAR and HCAR. Except for LVSP, the above-mentioned changes were more remarkable in HCAR than in LCAR(P【0.05). Myocyte interstitial CVF was positively correlated with the expression of IL-ip and TGF-β1(r=0.81 and 0.93, P【0.01), the activity of MMP-9 was obviously positively correlated with the expression of TNF-αand IL-β1(r=0.90 and 0.91, P 【0.01), and Rapo was positively correlated with the expression of TNF-α(r=0.88, P【0.01). Conclusions Left ventricle is undergoing progressive remodeling after CME due to abnormal expressions of pro-inflammatory and fibrogenic cytokines leading to myocyte apoptosis and interstitial collagen proliferation. Via down-regulating the expressions of these cytokines, Carvedilol intervention decreases myocyte apoptosis, interstitial collagen proliferation and improve ventricular function.
