Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via conc...Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via concomitant ligation of the left anterior descending （LAD） coronary artery and the circumflex （Cx） branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure （LVESP） and diastolic pressure （LVEDP） were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum （IVS） and the left ventricular posterior wall （LVPW） left ventricular end diastolic volume （LVEDV） and systolic volume （LVESV）, and ejection fraction （EF） were recorded by echo-cardiography. Results Thirty one （88.6%） rabbits survived myocardial infarction and 26 of them developed aneurysm （83.9%）. The mean area of aneurysm was 33.4% ＆#177; 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle （LV） that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%＆#177;2.4%which involves the apex, anterior wall and lateral wall of the LV.展开更多
Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reup...Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups： sham rabbits（controls, n=11）, rabbits with heart failure treated with Valsartan （n=11） and rabbits with heart failure but without Valsartan treatment （n=8）.Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography, SR calcium uptake was determined by measuring extra vesicular free [Ca2＋] changes in a fluorescence spectrophotometer. SERCA2a, Ser 16-phosphorylated phospholamban （p-PLB）, PKA and PP 1 a protein abundance were determined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased （P〈0.05）, these changes could be significantly attenuated by Valsartan treatment （P〈0.05）.Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes （P〈0.05）, with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP la in ventricular samples from the failing rabbits （P〈0.05）. All of these changes were attenuated by Valsartan treatment （all P〈0.05）. Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins （J Geriatr Cardio12009; 6：173-177）.展开更多
Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on t...Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current （Ito） and slow delayed rectifier potassium current （IKs）. Methods The monophasic action potential （MAP） technique was used to record the MAP duration of the epicardium （Epi）, myocardium （M） and endocardium （Endo） of the rabbit heart and the whole cell patch clamp was used to record/to and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization （TDR） in rabbit transmural ventricular wall. ALL decreased the current densities of/to and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation ofIto in M layers and partly inhibit the channel openings of/to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of tmnsmural inhibition of/to and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.展开更多
The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor （NGF...The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor （NGF） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks （HMI group, n=9）. Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion （HMI＋NGF group, 400 U/day for 8 weeks, n=8）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI＋NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF＋HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI＋NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.展开更多
Objective： To observe the influence of electroacupuncture （EA） of different Yuan- Primary acupoints on cardiac sympathetic nerve activity （CSNA） and cardiac function in rabbits with acute myocardial ischemia （AM...Objective： To observe the influence of electroacupuncture （EA） of different Yuan- Primary acupoints on cardiac sympathetic nerve activity （CSNA） and cardiac function in rabbits with acute myocardial ischemia （AMI）, and to understand the interaction mechanisms of cardiac sympathetic nerve in adjusting acute myocardial ischemia. Method： A total of forty healthy rabbits were selected and 8 were randomly chosen as normal control. The rest 32 rabbits were inducted acute myocardial ischemia （AMI） models by intravenous Pituitrin, then the AMI model rabbits were randomly divided into 4 groups, 8 as model group, and 8 as EA on Shenmen （HT 7） group, 8 as EA on Taixi （K/3） group, and 8 as EA on nonpoint group. BIOPAC collection system of biological signal was used to record the changes of CSNA and cardiac function, and the data was analyzed using a SKY-A8 disposal system. Result： The lefl ventricular systolic peak pressure （LVSP）, maximum rate of rise of LVSP （＋dp/dt max） descended obviously, and maximum rate of descent of LVSP （-dp/dt max） ascended after induction of AMI. The ＋dp/dt max, -dp/dt max and LVSP of EA on Shenmen （HT 7） group are significantly higher than the untreated AMI group, EA on Taixi （KI 3） group and EA on nonpoint group after EA. The frequency of cardiac sympathetic nerve activity increased significantly after induction of AMI, and then decreased sharply （compared with that of normal group, P〈0.05）. Following EA, the cardiac sympathetic nerve activity of EA on Shenmen （HT 7） group are significantly higher than the model group, EA on Taixi （KI 3） group and EA on nonpoint group. And they have no significant difference with normal group. Conclusion： EA on Shenmen （HT 7） could improve the cardiac function and cardiac sympathetic nerve activity of rabbits with AMI, and promote the restoration of cardiac function. There is specificity in the effects of EA on different Yuan-Primary acupoints with the best effect on Shenmen （HT 7）, and no effect on Taixi （KI 3） and nonpoint. EA on related acupoint can adjust the cardiac sympathetic nerve activity, and may moderate the effects of myocardial ischemia. The sympathetic nerve is one of the key periphery ways in using acupuncture against myocardial ischemia.展开更多
文摘Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via concomitant ligation of the left anterior descending （LAD） coronary artery and the circumflex （Cx） branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure （LVESP） and diastolic pressure （LVEDP） were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum （IVS） and the left ventricular posterior wall （LVPW） left ventricular end diastolic volume （LVEDV） and systolic volume （LVESV）, and ejection fraction （EF） were recorded by echo-cardiography. Results Thirty one （88.6%） rabbits survived myocardial infarction and 26 of them developed aneurysm （83.9%）. The mean area of aneurysm was 33.4% ＆#177; 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle （LV） that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%＆#177;2.4%which involves the apex, anterior wall and lateral wall of the LV.
基金This work was supported by National Natural Science Foundation of China （No 30800460）.
文摘Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups： sham rabbits（controls, n=11）, rabbits with heart failure treated with Valsartan （n=11） and rabbits with heart failure but without Valsartan treatment （n=8）.Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography, SR calcium uptake was determined by measuring extra vesicular free [Ca2＋] changes in a fluorescence spectrophotometer. SERCA2a, Ser 16-phosphorylated phospholamban （p-PLB）, PKA and PP 1 a protein abundance were determined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased （P〈0.05）, these changes could be significantly attenuated by Valsartan treatment （P〈0.05）.Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes （P〈0.05）, with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP la in ventricular samples from the failing rabbits （P〈0.05）. All of these changes were attenuated by Valsartan treatment （all P〈0.05）. Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins （J Geriatr Cardio12009; 6：173-177）.
文摘Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current （Ito） and slow delayed rectifier potassium current （IKs）. Methods The monophasic action potential （MAP） technique was used to record the MAP duration of the epicardium （Epi）, myocardium （M） and endocardium （Endo） of the rabbit heart and the whole cell patch clamp was used to record/to and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization （TDR） in rabbit transmural ventricular wall. ALL decreased the current densities of/to and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation ofIto in M layers and partly inhibit the channel openings of/to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of tmnsmural inhibition of/to and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.
基金Supported by the General Program of National Natural Science of China(30770901)
文摘The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor （NGF） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks （HMI group, n=9）. Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion （HMI＋NGF group, 400 U/day for 8 weeks, n=8）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI＋NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF＋HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI＋NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.
基金National Basic Research Program of China (973 Program, 2005CB523308)University Science Research Project of Anhui Province (KJ2009B200Z)
文摘Objective： To observe the influence of electroacupuncture （EA） of different Yuan- Primary acupoints on cardiac sympathetic nerve activity （CSNA） and cardiac function in rabbits with acute myocardial ischemia （AMI）, and to understand the interaction mechanisms of cardiac sympathetic nerve in adjusting acute myocardial ischemia. Method： A total of forty healthy rabbits were selected and 8 were randomly chosen as normal control. The rest 32 rabbits were inducted acute myocardial ischemia （AMI） models by intravenous Pituitrin, then the AMI model rabbits were randomly divided into 4 groups, 8 as model group, and 8 as EA on Shenmen （HT 7） group, 8 as EA on Taixi （K/3） group, and 8 as EA on nonpoint group. BIOPAC collection system of biological signal was used to record the changes of CSNA and cardiac function, and the data was analyzed using a SKY-A8 disposal system. Result： The lefl ventricular systolic peak pressure （LVSP）, maximum rate of rise of LVSP （＋dp/dt max） descended obviously, and maximum rate of descent of LVSP （-dp/dt max） ascended after induction of AMI. The ＋dp/dt max, -dp/dt max and LVSP of EA on Shenmen （HT 7） group are significantly higher than the untreated AMI group, EA on Taixi （KI 3） group and EA on nonpoint group after EA. The frequency of cardiac sympathetic nerve activity increased significantly after induction of AMI, and then decreased sharply （compared with that of normal group, P〈0.05）. Following EA, the cardiac sympathetic nerve activity of EA on Shenmen （HT 7） group are significantly higher than the model group, EA on Taixi （KI 3） group and EA on nonpoint group. And they have no significant difference with normal group. Conclusion： EA on Shenmen （HT 7） could improve the cardiac function and cardiac sympathetic nerve activity of rabbits with AMI, and promote the restoration of cardiac function. There is specificity in the effects of EA on different Yuan-Primary acupoints with the best effect on Shenmen （HT 7）, and no effect on Taixi （KI 3） and nonpoint. EA on related acupoint can adjust the cardiac sympathetic nerve activity, and may moderate the effects of myocardial ischemia. The sympathetic nerve is one of the key periphery ways in using acupuncture against myocardial ischemia.
