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GW27-e0959 Relaxant effect of salidroside on rat mesenteric artery and its calcium regulation mechanisms
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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
Groups were given Sal solution (15 or 30mg/kg/d) or the amount of normal saline through intraperitoneal injection 15 days. Con, EE group 0.9%NaCl were given (3ml/kg/d) intraperitoneal injection for 15 days. After the Sal pretreatment, the Con group did not do any exercise. EE, SEL and SEH groups’ rats were forced to swim until they were exhausted. The changes of ischemia modified albumin (IMA) in serum were observed by ELISA.TUNEL and semi quantitative analysis method was used to detect the myocardial cell apoptosis index (AI). Immunohistochemical method was used to detect myocardial Bax/ Bcl-2. Western blot method was used to detect the expression of myocardial Fas Cyto-c, Caspase-3, Caspase- 8, and Caspase- 9. RESULTS (1) The apoptosis index (AI) in EE group was increased significantly (EE: 36.002.00 VS Con: 27.004.32, P<0.05) compared with the Con group. Although the SEL group (35.608.26) was lower than the EE group, it was no statistical different (P>0.05). The SEH group (23.833.812) was the lowest than the EE and SEL group, the difference was statistically significant (P<0.05). (2) In terms of the serum levels of IMA, the EE, SEL and SEH group were significantly increased than Con group (P<0.05), the SEH and SEL group were reduced than the EE group (P<0.05), while the SEH group was significantly lower than that the SEL group (P<0.05). (3) Compared with the Con group in the Bax immunohistochemistry score, the EE and SEL group were increased (P<0.05). The SEH group was reduced evidently than the EE and SEL groups, and not significant different from the Con group. (4) Compared with the Con group, EE group, SEL group in the Bcl-2 immunohistochemistry score was significantly lower than the Bcl-2 group (P<0.05). The SEH group was increased significantly than the EE and SEL groups, and was slightly higher than the Con group but no statistical difference. (5)The Fas, Cyto-C and Caspase-3, Caspase-8, Caspase-9 myocardial expression quantity of the EE group, the SEL group and the SEH group wre increased significantly than the Con group (P<0.05). The EE group, the SEL group and the SEH group were reduced, and the difference between each other was statistically significant (P<0.05). CONCLUSIONS Salidroside can significantly reduce the myocardial ischemia and reduce myocardial cell apoptosis in exhaustive exercise rats. The mechanism may be related to inhibit the expression of Bax, Fas, Cyto-C, Caspase-3, Caspase-8, Caspase-9 and increase Bcl-2. GW27-e0912 Cardioprotective effects of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury Mu Fei, Jialin Duan, Miaomiao Xi Xijing Hospital, Fourth Military Medical University OBJECTIVES This study was designed to investigate the cardioprotective effects and potential mechanism of SM and DO on rat myocardial ischemia/reperfusion (MI/R) injury. METHODS Sprague-Dawley rats were pretreated with Radix salviae miltiorrhizae (SM), aqueous extract of Lignum dalbergiae odoriferae (DOA) and volatile oil of Lignum dalbergiae odoriferae (DOO), either as monotherapy or in combination for 7 days, then subjected to 30 min of ischemia followed by 180 min of reperfusion. Infarct area, myocardial marker enzymes, apoptosis, oxidative stress and inflammatory factors were determined by proper methods. Moreover, metabonomics based on GC-TOF-MS was used to identify the therapeutic effect of these TCM. RESULTS he results showed that SM, DOA and DOO ameliorated cardiac function respectively, and this effect was further strengthened by their combinations. Among all combinations, SMþDOO showed predominant potential (P<0.01) to improve electrocardiogram and heart rate, reduce heart weight index and myocardial infarct size, decrease the levels of CK-MB and LDH. Moreover, metabonomicsbased findings such as the PCA and PLS-DA score plot of metabolic state in rat serum correlated well to the preceding results, confirming that SMþDOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups. Furthermore, the maximum effective point of SMþDOO was 30min and the minimum effective point was 180min. In addition, SMþDOO group markedly (P<0.01) reduced the number of TUNELpositive cells, the levels of TNF-a, IL-6 and MDA, whileincreased the activity of SOD both in serum and tissue. CONCLUSIONS These results indicated that SMþDOO have combined effects that are highly effective than single pretreatment against MI/R injury rats. This effect might be achieved partly through
anti-apoptosis, anti-oxidant and anti-inflammatory. Thus SMþDOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease. GW27-e0945 Cardiovascular progenitor-derived extracellular vesicles benefit their parent cells in the treatment of chronic heart failure Jie Qin,1 Songwang Cai,2 Lingrong Peng,1 Wenjie Tang1 Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University; 2Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Sun Yat-sen University 1
OBJECTIVES To assess whether post-infarction administration of extracellular vesicles (EV) released by human embryonic stem cellderived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. METHODS Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. Functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. RESULTS At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.78 0.68 ml or -7.9%, p ¼ 0.0007) and end-diastolic (-4.88 1.62 ml or -5.8%, p ¼ 0.008) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EVtreated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. CONCLUSIONS Either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. A paracrine mechanism is sufficient to affect functional recovery in cell-based therapies for postinfarction-related chronic heart failure. GW27-e0959 Relaxant effect of salidroside on rat mesenteric artery and its calcium regulation mechanisms Sun Weiwei, Xuebin Cao No.252 Hospital of PLA OBJECTIVES To investigate relaxant effect of salidroside (SAL) on rat mesenteric artery, and to explore its calcium regulation mechanisms． METHODS Tension was measured by DMT 620M system to evaluate the relaxant effect of SAL on rat mesenteric artery rings. Calcium deprivation and calcium addition were used . Besides, for protein assay, 20 adult male Sprague Dawley SD rats were randomly divided into control group (Con), salidroside group (SAL).The protein expression of IP3R1 and RyR2 were determined by Western blotting. RESULTS ①With calcium deprivation and calcium addition, SAL relaxed endothelium-denuded mesenteric artery precontracted by PE (1mmol$L-1) (P<0.01 in 10-5 mol$L-1 SAL), while SAL had no effect on the increasing tension of mesenteric artery induced by adding CaCl2.② In SAL group SAL significantly reduced the expression of IP3R1, and increased the expression of RyR2 (P<0.01). CONCLUSIONS These results indicate that SAL mainly relaxes mesenteric artery by inhibiting the expression of IP3R1 and then inhibition of intracellular calcium release, in spite of the increase of
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
theexpression of RyR2. Besides, this vasodilation effect of SAL may be not associated with influx of extracellular calcium. GW27-e1012 Up-regulation of caveolin-1 suppresses vascular smooth muscle cells proliferation and neointimal formation in balloon injured rat carotid artery Lu Wei, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES Caveolin-1(cav-1) is the major coat protein responsible for caveolae assembly, regulating signaling via protein-protein interactions with resident caveolar proteins, but its biological mechanism in vascular smooth muscle cells (VSMCs) is still unclear. The aim of this study was to evaluate the role of cav-1 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery. METHODS Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 30 mL solution of Ad-cav-1 adenoviral vectors, Ad-GFP adenoviral vectors or PBS for 30 min. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with Ad-cav-1 or Ad-GFP adenoviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. The vascular or intracellular ROS level was also detected. RESULTS Adenoviral vectors encoding cav-1 cDNA could increase cav-1 expression both in mRNA and protein levels in balloon injured artery walls and cultured rat VSMCs. Upregulation of cav-1 significantly suppressed VSMCs proliferation and intimal formation. Overexpression of cav-1 could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs. CONCLUSIONS Our study suggests that over-expression of cav-1 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury. GW27-e1017 Beneficial effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia-reperfusion injury in rats Song Mingbao, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES to explore the effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia-reperfusion injury in rats. METHODS In the present study, one water-soluble polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. The cardioprotective potential of SMP1 was studied in the ischemia-reperfusion (I/R) model of rats in vivo. RESULTS Results showed that 30 min of left anterior descending coronary artery occlusion (LAD) followed by 4 h of reperfusion markedly decreased myocardial superoxide dismutase (SOD), Na(þ)K(þ)-ATPase and Ca(2þ)-Mg(2þ)-ATPase activities and increased myocardial malondialdehyde (MDA) level and serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in I/R rats. An increase in infarct size and high apoptosis index of cardiac cell were also observed in IR rats. Administration of SMP1 400 and 800 mg/kg significantly reversed these biochemical parameters in the I/R rats to the normal levels in sham control rats. The infarct sizes and the percent of TUNEL-positive cells were found significantly decreased in SMP1-treated groups compared to I/R rats. CONCLUSIONS Taken together, the present study clearly suggests SMP1 has a protective effect against myocardial I/R injury in rats by ameliorating oxidative stress and inhibiting myocardial apoptosis. GW27-e1105 Endothelin-1 in Left Stellate Ganglion Promotes Post-infarction Ventricular Arrhythmias by Increasing Cardiac Sympathetic Activity Zhou Liping,1,2,3 Lilei Yu,1,2,3 Hong Jiang1,2,3 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, PR China; 3Hubei Key Laboratory of Cardiology, Wuhan, PR China
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OBJECTIVES Paraventricular Nucleus (PVN) and Left stellate ganglion (LSG) are important central and peripheral components of cardiac sympathetic afferent reflex (CSAR) respectively. Studies have shown that endothelin-1 (ET-1) in PVN could increase sympathetic activity and elevated plasma level of ET-1 was related with ventricular arrhythmias (VAs). This study aimed to investigate whether ET-1 in LSG could increase cardiac sympathetic activity and thus facilitate post-infarction VAs in a canine model. METHODS Twelve anesthetized open-chest male beagle dogs were randomly divided into the ET-1 group (n¼6) and the control group (n¼6). ET-1 (0.1ml, 0.1umol/ml) or saline (0.1ml) was microinjected into LSG separately. Ventricular effective refractory period (ERP), heart rate variability (HRV), LSG function and neural activity, serum norepinephrine (NE) level were measured at baseline and 30min after ET-1 injection. Then myocardial infarction (MI) was induced by ligating left anterior descending coronary artery. HRV, LSG neural activity and serum NE levels were measured 1h after MI. VAs occurred during the first hour after MI were recorded. RESULTS Compared to baseline, ET-1 microinjection significantly increased LSG function and neural activity and serum NE level, decreased HRV, shortened ventricular ERP, whereas, no significant changes of these indices were shown in the control group. MI induced a more significant decrease in HRV and increase in LSG neural activity and NE levels in the ET-1 group than those in the control group. The incidence of VAs was significantly higher in the ET-1 group than that in the control group. CONCLUSIONS ET-1 in LSG may increase the cardiac sympathetic activity and thus facilitate MI-induced VAs.
GW27-e1111 Renal sympathetic denervation prevents ventricular tachycardia in a canine model of drug-induced long-QT syndrome type 1 Huang Bing,1,2,3 Lilei Yu,1,2,3 Hong Jiang1,2,3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; 2Cardiovascular Research Institute of Wuhan University, Wuhan, China; 3Hubei Key Laboratory of Cardiology, Wuhan, China 1
OBJECTIVES Increased sympathetic activity precipitates ventricular tachyarrhythmias and sudden cardiac death in long-QT syndrome type 1 (LQT1). Renal sympathetic denervation (RDN) has emerged as a new approach to reduce sympathetic activity. This study aimed to investigate whether RDN could prevent ventricular tachycardia in a canine model of drug-induced LQT1. METHODS Fourteen adult beagle dogs were randomly assigned into control group (n¼7) and RDN group (n¼7). ECGs, blood pressure and left stellate ganglion (LSG) neural activity were continuously recorded. The LQT1 model was constructed by infusion of the slowlyactivating delayed-rectifier Kþ current (IKs) blocker HMR1556 (0.05 mg/kg/min). In RDN group, RDN was performed 30 minutes before the administration of HMR1556 by radiofrequency ablation of the adventitial surface of the renal artery. In both groups, ventricular effective refractory period (ERP), action potential duration (APD), and APD restitution properties were determined at baseline and 15 min after infusion of HMR1556, and then bolus injections of isoproterenol (2.5 ug/kg) were performed to trigger torsades de pointes (TdP). RESULTS In both groups, infusion of HMR1556 for 15 minutes significantly prolonged the QT interval, ventricular ERP and APD. Besides, in the control group, infusion of HMR1556 dramatically increased the spatial dispersion of repolarization (TpeakTend interval) and the maximal slopes of the APD restitution curves (Smax), which, however, were attenuated by RDN. Bolus injection of isoproterenol significantly increased LSG neural activity, evoked paradoxical repolarization prolongation during heart rate accelerations, and triggered the occurrence of TdP in the control group. However, RDN also significantly attenuated the activation of LSG and the occurrence of TdP during bolus injection of isoproterenol when compared to the control group. CONCLUSIONS RDN could prevent ventricular tachycardia in this model of drug-induced LQT1.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
Groups were given Sal solution (15 or 30mg/kg/d) or the amount of normal saline through intraperitoneal injection 15 days. Con, EE group 0.9%NaCl were given (3ml/kg/d) intraperitoneal injection for 15 days. After the Sal pretreatment, the Con group did not do any exercise. EE, SEL and SEH groups’ rats were forced to swim until they were exhausted. The changes of ischemia modified albumin (IMA) in serum were observed by ELISA.TUNEL and semi quantitative analysis method was used to detect the myocardial cell apoptosis index (AI). Immunohistochemical method was used to detect myocardial Bax/ Bcl-2. Western blot method was used to detect the expression of myocardial Fas Cyto-c, Caspase-3, Caspase- 8, and Caspase- 9. RESULTS (1) The apoptosis index (AI) in EE group was increased significantly (EE: 36.002.00 VS Con: 27.004.32, P<0.05) compared with the Con group. Although the SEL group (35.608.26) was lower than the EE group, it was no statistical different (P>0.05). The SEH group (23.833.812) was the lowest than the EE and SEL group, the difference was statistically significant (P<0.05). (2) In terms of the serum levels of IMA, the EE, SEL and SEH group were significantly increased than Con group (P<0.05), the SEH and SEL group were reduced than the EE group (P<0.05), while the SEH group was significantly lower than that the SEL group (P<0.05). (3) Compared with the Con group in the Bax immunohistochemistry score, the EE and SEL group were increased (P<0.05). The SEH group was reduced evidently than the EE and SEL groups, and not significant different from the Con group. (4) Compared with the Con group, EE group, SEL group in the Bcl-2 immunohistochemistry score was significantly lower than the Bcl-2 group (P<0.05). The SEH group was increased significantly than the EE and SEL groups, and was slightly higher than the Con group but no statistical difference. (5)The Fas, Cyto-C and Caspase-3, Caspase-8, Caspase-9 myocardial expression quantity of the EE group, the SEL group and the SEH group wre increased significantly than the Con group (P<0.05). The EE group, the SEL group and the SEH group were reduced, and the difference between each other was statistically significant (P<0.05). CONCLUSIONS Salidroside can significantly reduce the myocardial ischemia and reduce myocardial cell apoptosis in exhaustive exercise rats. The mechanism may be related to inhibit the expression of Bax, Fas, Cyto-C, Caspase-3, Caspase-8, Caspase-9 and increase Bcl-2. GW27-e0912 Cardioprotective effects of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury Mu Fei, Jialin Duan, Miaomiao Xi Xijing Hospital, Fourth Military Medical University OBJECTIVES This study was designed to investigate the cardioprotective effects and potential mechanism of SM and DO on rat myocardial ischemia/reperfusion (MI/R) injury. METHODS Sprague-Dawley rats were pretreated with Radix salviae miltiorrhizae (SM), aqueous extract of Lignum dalbergiae odoriferae (DOA) and volatile oil of Lignum dalbergiae odoriferae (DOO), either as monotherapy or in combination for 7 days, then subjected to 30 min of ischemia followed by 180 min of reperfusion. Infarct area, myocardial marker enzymes, apoptosis, oxidative stress and inflammatory factors were determined by proper methods. Moreover, metabonomics based on GC-TOF-MS was used to identify the therapeutic effect of these TCM. RESULTS he results showed that SM, DOA and DOO ameliorated cardiac function respectively, and this effect was further strengthened by their combinations. Among all combinations, SMþDOO showed predominant potential (P<0.01) to improve electrocardiogram and heart rate, reduce heart weight index and myocardial infarct size, decrease the levels of CK-MB and LDH. Moreover, metabonomicsbased findings such as the PCA and PLS-DA score plot of metabolic state in rat serum correlated well to the preceding results, confirming that SMþDOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups. Furthermore, the maximum effective point of SMþDOO was 30min and the minimum effective point was 180min. In addition, SMþDOO group markedly (P<0.01) reduced the number of TUNELpositive cells, the levels of TNF-a, IL-6 and MDA, whileincreased the activity of SOD both in serum and tissue. CONCLUSIONS These results indicated that SMþDOO have combined effects that are highly effective than single pretreatment against MI/R injury rats. This effect might be achieved partly through
anti-apoptosis, anti-oxidant and anti-inflammatory. Thus SMþDOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease. GW27-e0945 Cardiovascular progenitor-derived extracellular vesicles benefit their parent cells in the treatment of chronic heart failure Jie Qin,1 Songwang Cai,2 Lingrong Peng,1 Wenjie Tang1 Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University; 2Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Sun Yat-sen University 1
OBJECTIVES To assess whether post-infarction administration of extracellular vesicles (EV) released by human embryonic stem cellderived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. METHODS Mice underwent surgical occlusion of their left coronary arteries. After 2-3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. Functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg-treated and EV-treated hearts were clustered into functionally relevant pathways. RESULTS At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (-4.78 0.68 ml or -7.9%, p ¼ 0.0007) and end-diastolic (-4.88 1.62 ml or -5.8%, p ¼ 0.008) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell-derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg-derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg-treated animals and EV-treated animals compared with alpha-MEM-treated control animals. In the hESC-Pg-treated and EVtreated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. CONCLUSIONS Either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. A paracrine mechanism is sufficient to affect functional recovery in cell-based therapies for postinfarction-related chronic heart failure. GW27-e0959 Relaxant effect of salidroside on rat mesenteric artery and its calcium regulation mechanisms Sun Weiwei, Xuebin Cao No.252 Hospital of PLA OBJECTIVES To investigate relaxant effect of salidroside (SAL) on rat mesenteric artery, and to explore its calcium regulation mechanisms． METHODS Tension was measured by DMT 620M system to evaluate the relaxant effect of SAL on rat mesenteric artery rings. Calcium deprivation and calcium addition were used . Besides, for protein assay, 20 adult male Sprague Dawley SD rats were randomly divided into control group (Con), salidroside group (SAL).The protein expression of IP3R1 and RyR2 were determined by Western blotting. RESULTS ①With calcium deprivation and calcium addition, SAL relaxed endothelium-denuded mesenteric artery precontracted by PE (1mmol$L-1) (P<0.01 in 10-5 mol$L-1 SAL), while SAL had no effect on the increasing tension of mesenteric artery induced by adding CaCl2.② In SAL group SAL significantly reduced the expression of IP3R1, and increased the expression of RyR2 (P<0.01). CONCLUSIONS These results indicate that SAL mainly relaxes mesenteric artery by inhibiting the expression of IP3R1 and then inhibition of intracellular calcium release, in spite of the increase of
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, VOL. 68, NO. 16, SUPPL S, 2016
theexpression of RyR2. Besides, this vasodilation effect of SAL may be not associated with influx of extracellular calcium. GW27-e1012 Up-regulation of caveolin-1 suppresses vascular smooth muscle cells proliferation and neointimal formation in balloon injured rat carotid artery Lu Wei, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES Caveolin-1(cav-1) is the major coat protein responsible for caveolae assembly, regulating signaling via protein-protein interactions with resident caveolar proteins, but its biological mechanism in vascular smooth muscle cells (VSMCs) is still unclear. The aim of this study was to evaluate the role of cav-1 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery. METHODS Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 30 mL solution of Ad-cav-1 adenoviral vectors, Ad-GFP adenoviral vectors or PBS for 30 min. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with Ad-cav-1 or Ad-GFP adenoviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. The vascular or intracellular ROS level was also detected. RESULTS Adenoviral vectors encoding cav-1 cDNA could increase cav-1 expression both in mRNA and protein levels in balloon injured artery walls and cultured rat VSMCs. Upregulation of cav-1 significantly suppressed VSMCs proliferation and intimal formation. Overexpression of cav-1 could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs. CONCLUSIONS Our study suggests that over-expression of cav-1 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury. GW27-e1017 Beneficial effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia-reperfusion injury in rats Song Mingbao, Lan Huang The Institute of Cardiovascular Disease of PLA, Xin Qiao Hospital, Third Military Medical University OBJECTIVES to explore the effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia-reperfusion injury in rats. METHODS In the present study, one water-soluble polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. The cardioprotective potential of SMP1 was studied in the ischemia-reperfusion (I/R) model of rats in vivo. RESULTS Results showed that 30 min of left anterior descending coronary artery occlusion (LAD) followed by 4 h of reperfusion markedly decreased myocardial superoxide dismutase (SOD), Na(þ)K(þ)-ATPase and Ca(2þ)-Mg(2þ)-ATPase activities and increased myocardial malondialdehyde (MDA) level and serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in I/R rats. An increase in infarct size and high apoptosis index of cardiac cell were also observed in IR rats. Administration of SMP1 400 and 800 mg/kg significantly reversed these biochemical parameters in the I/R rats to the normal levels in sham control rats. The infarct sizes and the percent of TUNEL-positive cells were found significantly decreased in SMP1-treated groups compared to I/R rats. CONCLUSIONS Taken together, the present study clearly suggests SMP1 has a protective effect against myocardial I/R injury in rats by ameliorating oxidative stress and inhibiting myocardial apoptosis. GW27-e1105 Endothelin-1 in Left Stellate Ganglion Promotes Post-infarction Ventricular Arrhythmias by Increasing Cardiac Sympathetic Activity Zhou Liping,1,2,3 Lilei Yu,1,2,3 Hong Jiang1,2,3 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, PR China; 3Hubei Key Laboratory of Cardiology, Wuhan, PR China
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OBJECTIVES Paraventricular Nucleus (PVN) and Left stellate ganglion (LSG) are important central and peripheral components of cardiac sympathetic afferent reflex (CSAR) respectively. Studies have shown that endothelin-1 (ET-1) in PVN could increase sympathetic activity and elevated plasma level of ET-1 was related with ventricular arrhythmias (VAs). This study aimed to investigate whether ET-1 in LSG could increase cardiac sympathetic activity and thus facilitate post-infarction VAs in a canine model. METHODS Twelve anesthetized open-chest male beagle dogs were randomly divided into the ET-1 group (n¼6) and the control group (n¼6). ET-1 (0.1ml, 0.1umol/ml) or saline (0.1ml) was microinjected into LSG separately. Ventricular effective refractory period (ERP), heart rate variability (HRV), LSG function and neural activity, serum norepinephrine (NE) level were measured at baseline and 30min after ET-1 injection. Then myocardial infarction (MI) was induced by ligating left anterior descending coronary artery. HRV, LSG neural activity and serum NE levels were measured 1h after MI. VAs occurred during the first hour after MI were recorded. RESULTS Compared to baseline, ET-1 microinjection significantly increased LSG function and neural activity and serum NE level, decreased HRV, shortened ventricular ERP, whereas, no significant changes of these indices were shown in the control group. MI induced a more significant decrease in HRV and increase in LSG neural activity and NE levels in the ET-1 group than those in the control group. The incidence of VAs was significantly higher in the ET-1 group than that in the control group. CONCLUSIONS ET-1 in LSG may increase the cardiac sympathetic activity and thus facilitate MI-induced VAs.
GW27-e1111 Renal sympathetic denervation prevents ventricular tachycardia in a canine model of drug-induced long-QT syndrome type 1 Huang Bing,1,2,3 Lilei Yu,1,2,3 Hong Jiang1,2,3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; 2Cardiovascular Research Institute of Wuhan University, Wuhan, China; 3Hubei Key Laboratory of Cardiology, Wuhan, China 1
OBJECTIVES Increased sympathetic activity precipitates ventricular tachyarrhythmias and sudden cardiac death in long-QT syndrome type 1 (LQT1). Renal sympathetic denervation (RDN) has emerged as a new approach to reduce sympathetic activity. This study aimed to investigate whether RDN could prevent ventricular tachycardia in a canine model of drug-induced LQT1. METHODS Fourteen adult beagle dogs were randomly assigned into control group (n¼7) and RDN group (n¼7). ECGs, blood pressure and left stellate ganglion (LSG) neural activity were continuously recorded. The LQT1 model was constructed by infusion of the slowlyactivating delayed-rectifier Kþ current (IKs) blocker HMR1556 (0.05 mg/kg/min). In RDN group, RDN was performed 30 minutes before the administration of HMR1556 by radiofrequency ablation of the adventitial surface of the renal artery. In both groups, ventricular effective refractory period (ERP), action potential duration (APD), and APD restitution properties were determined at baseline and 15 min after infusion of HMR1556, and then bolus injections of isoproterenol (2.5 ug/kg) were performed to trigger torsades de pointes (TdP). RESULTS In both groups, infusion of HMR1556 for 15 minutes significantly prolonged the QT interval, ventricular ERP and APD. Besides, in the control group, infusion of HMR1556 dramatically increased the spatial dispersion of repolarization (TpeakTend interval) and the maximal slopes of the APD restitution curves (Smax), which, however, were attenuated by RDN. Bolus injection of isoproterenol significantly increased LSG neural activity, evoked paradoxical repolarization prolongation during heart rate accelerations, and triggered the occurrence of TdP in the control group. However, RDN also significantly attenuated the activation of LSG and the occurrence of TdP during bolus injection of isoproterenol when compared to the control group. CONCLUSIONS RDN could prevent ventricular tachycardia in this model of drug-induced LQT1.