Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endot...Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2+-activated K+ (BK) channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents (defined as the iberiotoxin-sensitive K+ component) contribute (65+4)% of the total K+currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2+ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel i~ subunit activator) robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2+ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2+. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2+ concentration of coronary arterial smooth muscle cells was increased from (103±23) nmol/L (n=5) of control rats to (193±22) nmol/L (n=6, P 〈0.05) of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2+, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.展开更多
Background It is welt known that increased cumulative ventricular pacing proportion (CumVP%) is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatmen...Background It is welt known that increased cumulative ventricular pacing proportion (CumVP%) is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers. Methods Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing (DDDR), search atrioventricular conduction plus (SAV+) and managed ventricular pacing (MVP), were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV+ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense (AS-VS), atrial sense-ventricular pacing (AS-VP), atrial pacing-ventricular sense (AP-VS) and atrial pacing-ventricular pacing (AP-VP) were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively. Results In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV+ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV+ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively (P〈0.05) and the percentages of CumVP% 〈40% in patients were 0, 23.8% and 95.2.0% (P〈0.05). Conclusions Compared with the conventional DDDR algorithm, both SAY+ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%.展开更多
In recent years, the indications of cardiac pacing have extended continuously with the rapid development of pacing technique. Pacemaker treatment has not only limited in arrhythmias of bradycardia and the number of pa...In recent years, the indications of cardiac pacing have extended continuously with the rapid development of pacing technique. Pacemaker treatment has not only limited in arrhythmias of bradycardia and the number of pacemaker treatment has increased year by year. However, more and more new congestive heart failure ( CHF ) and aggravated CHF have appeared in patients after pacing therapy. Therefore, it is a hot topic that how to select reasonable pacing mode to reduce CHF occurrence or relieve CHF symptoms in patients with CHF.展开更多
Background Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for advanced heart failure patients; however, a number of key clinical research questions remain, perhaps most importantly the is...Background Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for advanced heart failure patients; however, a number of key clinical research questions remain, perhaps most importantly the issue of why apparently suitable patients do not respond to CRT. Methods Seven patients, six males and one female, aged (56.43±6.13) years, all diagnosed with dilated cardiomyopathy, were included in this study. They were all non-responders to CRT who underwent routine optimization postoperatively, and received optimal drug therapy. On the basis of biventricular pacing, titrating various atrioventricular (AV) intervals were performed to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction. Then, the effects of AV intrinsic conduction during CRT were evaluated. Results On the setting of AV intrinsic conduction during CRT, the true fusional QRS complexes were the narrowest, and all patients showed alleviation of symptoms, improvement of exercise tolerance, life quality and hemodynamic parameters during more than 6 months of follow-up. Conclusions Titrating AV intervals to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction will be beneficial for non-responders to CRT. Maintaining AV intrinsic conduction during CRT may decrease the rates of non-resoonders to CRT.展开更多
Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for patients with advanced congestive heart failure, however, a number of key clinical research questions remain, perhaps most importantly t...Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for patients with advanced congestive heart failure, however, a number of key clinical research questions remain, perhaps most importantly the issue of why apparently suitable patients do not respond to CRT. These issues are also relevant to patients who do respond to CRT as potentially their response might be further increased. Though patients do not respond to CRT because of many known postulated reasons, we review the importance of maintaining atrioventricular intrinsic conduction during CRT in this paper, which maybe is one of methods to reduce the rates of non-response to CRT.展开更多
基金the National Natural Science Foundation of China,Natural Science Foundation of Jiangsu Province,Medical Key Personnel of Jiangsu Province,Top Qualified Personnel in Six Fields of Jiangsu Province (006) to WANG Ru-xing and the American Diabetes Association Junior Faculty Awards
文摘Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2+-activated K+ (BK) channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents (defined as the iberiotoxin-sensitive K+ component) contribute (65+4)% of the total K+currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2+ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel i~ subunit activator) robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2+ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2+. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2+ concentration of coronary arterial smooth muscle cells was increased from (103±23) nmol/L (n=5) of control rats to (193±22) nmol/L (n=6, P 〈0.05) of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2+, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.
文摘Background It is welt known that increased cumulative ventricular pacing proportion (CumVP%) is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers. Methods Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing (DDDR), search atrioventricular conduction plus (SAV+) and managed ventricular pacing (MVP), were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV+ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense (AS-VS), atrial sense-ventricular pacing (AS-VP), atrial pacing-ventricular sense (AP-VS) and atrial pacing-ventricular pacing (AP-VP) were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively. Results In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV+ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV+ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively (P〈0.05) and the percentages of CumVP% 〈40% in patients were 0, 23.8% and 95.2.0% (P〈0.05). Conclusions Compared with the conventional DDDR algorithm, both SAY+ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%.
文摘In recent years, the indications of cardiac pacing have extended continuously with the rapid development of pacing technique. Pacemaker treatment has not only limited in arrhythmias of bradycardia and the number of pacemaker treatment has increased year by year. However, more and more new congestive heart failure ( CHF ) and aggravated CHF have appeared in patients after pacing therapy. Therefore, it is a hot topic that how to select reasonable pacing mode to reduce CHF occurrence or relieve CHF symptoms in patients with CHF.
文摘Background Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for advanced heart failure patients; however, a number of key clinical research questions remain, perhaps most importantly the issue of why apparently suitable patients do not respond to CRT. Methods Seven patients, six males and one female, aged (56.43±6.13) years, all diagnosed with dilated cardiomyopathy, were included in this study. They were all non-responders to CRT who underwent routine optimization postoperatively, and received optimal drug therapy. On the basis of biventricular pacing, titrating various atrioventricular (AV) intervals were performed to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction. Then, the effects of AV intrinsic conduction during CRT were evaluated. Results On the setting of AV intrinsic conduction during CRT, the true fusional QRS complexes were the narrowest, and all patients showed alleviation of symptoms, improvement of exercise tolerance, life quality and hemodynamic parameters during more than 6 months of follow-up. Conclusions Titrating AV intervals to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction will be beneficial for non-responders to CRT. Maintaining AV intrinsic conduction during CRT may decrease the rates of non-resoonders to CRT.
文摘Cardiac resynchronization therapy (CRT) is a major breakthrough in therapy for patients with advanced congestive heart failure, however, a number of key clinical research questions remain, perhaps most importantly the issue of why apparently suitable patients do not respond to CRT. These issues are also relevant to patients who do respond to CRT as potentially their response might be further increased. Though patients do not respond to CRT because of many known postulated reasons, we review the importance of maintaining atrioventricular intrinsic conduction during CRT in this paper, which maybe is one of methods to reduce the rates of non-response to CRT.