1.The Role of the Calcium and the Voltage Clocks in Sinoatrial Node Dysfunction.
Boyoung JOUNG ; Peng Sheng CHEN ; Shien Fong LIN
Yonsei Medical Journal 2011;52(2):211-219
Recent evidence indicates that the voltage clock (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release) jointly regulate sinoatrial node (SAN) automaticity. However, the relative importance of the voltage clock and Ca2+ clock for pacemaking was not revealed in sick sinus syndrome. Previously, we mapped the intracellular calcium (Cai) and membrane potentials of the normal intact SAN simultaneously using optical mapping in Langendorff-perfused canine right atrium. We demonstrated that the sinus rate increased and the leading pacemaker shifted to the superior SAN with robust late diastolic Cai elevation (LDCAE) during beta-adrenergic stimulation. We also showed that the LDCAE was caused by spontaneous diastolic sarcoplasmic reticulum (SR) Ca2+ release and was closely related to heart rate changes. In contrast, in pacing induced canine atrial fibrillation and SAN dysfunction models, Ca2+ clock of SAN was unresponsiveness to beta-adrenergic stimulation and caffeine. Ryanodine receptor 2 (RyR2) in SAN was down-regulated. Using the prolonged low dose isoproterenol together with funny current block, we produced a tachybradycardia model. In this model, chronically elevated sympathetic tone results in abnormal pacemaking hierarchy in the right atrium, including suppression of the superior SAN and enhanced pacemaking from ectopic sites. Finally, if the LDCAE was too small to trigger an action potential, then it induced only delayed afterdepolarization (DAD)-like diastolic depolarization (DD). The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis. We conclude that dysfunction of both the Ca2+ clock and the voltage clock are important in sick sinus syndrome.
Animals
;
Arrhythmia, Sinus/physiopathology
;
Atrial Fibrillation/physiopathology
;
Bradycardia/physiopathology
;
Calcium/*physiology
;
Calcium Channels/*physiology
;
Dogs
;
Humans
;
Sick Sinus Syndrome/physiopathology
;
Sinoatrial Node/physiology/*physiopathology
2.Experimental study of assessment on ventricular activation origin and contraction sequence by Doppler tissue imaging.
Ruiping JI ; Xinfang WANG ; Tsung O CHENG ; Wangpeng LIU ; Zhi'an LI ; Li LIU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(1):52-57
To evaluate the possibility and accuracy of Doppler tissue image (DTI) on assessment of normal and abnormal ventricular activation and contraction sequence, 9 open chest canine hearts were analyzed by acceleration mode, M-mode, and spectrum mode DTI. Our results showed that: (1) Acceleration mode DTI could show the origin of activation and conduction sequence on line; (2) M-mode DTI revealed that the activation in mid-interventricular septum was earlier than that in mid-left ventricular posterior wall at sinus activation; (3) Spectrum DTI showed the ventricular endocardium was activated earlier than the ventricular epicardium in all segments at sinus rhythm. The earliest site of activation of the normal ventricular wall was at middle interventricular septum; the latest site was at basal-posterior wall; the contraction sequence was different at the different walls; (4) During abnormal ventricular activation, mid-left ventricular posterior wall was activated earliest in accordance with the pacing sites. Abnormal ventricular activation was slower than sinus activation, and the contraction sequence varied at different sites of ventricular wall. It is concluded that DTI can be used to localize the origin of normal or abnormal myocardial activation and to assess the contraction sequence conveniently, accurately and non-invasively.
Animals
;
Dogs
;
Echocardiography, Doppler
;
instrumentation
;
methods
;
Heart Ventricles
;
diagnostic imaging
;
Myocardial Contraction
;
physiology
;
Sinoatrial Node
;
physiology
;
Tachycardia
;
diagnostic imaging
;
physiopathology
3.Instantaneous chaometry applied in heart rate study.
Chuanwen LUO ; Chuanhui LIU ; Gang WANG ; Hua SHEN ; Xianhe WEI
Journal of Biomedical Engineering 2008;25(3):703-707
Instantaneous chaometry was defined on uniformity theory constructed by the present authors. The sample data, sinus heart rate data and arrhythmia heart rate data from MIT-BIH were analyzed with instantaneous chaometry (ICM); the situation not being distinguished with HRV can be differentiated with ICM. The normal sinus rhythm was found to be of three evident characteristics: (1) instant returning to zero, (2) stability-stable characteristic of ICM on the initial position, (3) interval of mean: 2-7, variance: 1.5-5. The third characteristic shows that the variability of ICM is necessary. The studies on arrhythmia database showed that arrhythmia cases exhibited no returning to zero, nonstability of ICM on the initial position, too small mean or standard deviation, respectively. Evidently, the arithmetic of ICM is simple; ICM can be easily applied in clinical and pathologic analyses.
Arrhythmias, Cardiac
;
physiopathology
;
Electrocardiography
;
methods
;
Heart Rate
;
physiology
;
Humans
;
Male
;
Middle Aged
;
Signal Processing, Computer-Assisted
;
Sinoatrial Node
;
physiology
4.Experimental study of assessment on ventricular activation origin and contraction sequence by Doppler tissue imaging.
Ruiping, JI ; Xinfang, WANG ; Tsung O, CHENG ; Wangpeng, LIU ; Zhi'an, LI ; Li, LIU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(1):52-7
To evaluate the possibility and accuracy of Doppler tissue image (DTI) on assessment of normal and abnormal ventricular activation and contraction sequence, 9 open chest canine hearts were analyzed by acceleration mode, M-mode, and spectrum mode DTI. Our results showed that: (1) Acceleration mode DTI could show the origin of activation and conduction sequence on line; (2) M-mode DTI revealed that the activation in mid-interventricular septum was earlier than that in mid-left ventricular posterior wall at sinus activation; (3) Spectrum DTI showed the ventricular endocardium was activated earlier than the ventricular epicardium in all segments at sinus rhythm. The earliest site of activation of the normal ventricular wall was at middle interventricular septum; the latest site was at basal-posterior wall; the contraction sequence was different at the different walls; (4) During abnormal ventricular activation, mid-left ventricular posterior wall was activated earliest in accordance with the pacing sites. Abnormal ventricular activation was slower than sinus activation, and the contraction sequence varied at different sites of ventricular wall. It is concluded that DTI can be used to localize the origin of normal or abnormal myocardial activation and to assess the contraction sequence conveniently, accurately and non-invasively.
Echocardiography, Doppler/instrumentation
;
Echocardiography, Doppler/*methods
;
Heart Ventricles/*ultrasonography
;
Myocardial Contraction/*physiology
;
Sinoatrial Node/physiology
;
Tachycardia/physiopathology
;
Tachycardia/ultrasonography
5.Study on the effect of Klotho gene interferred by plasmid-mediated short hairpin RNA (shRNA) on sinoatrial node pacing channel gene.
Yingying CAI ; Han WANG ; Yanbin HOU ; Chenli FANG ; Peng TIAN ; Guihua WANG ; Lu LI ; Juelin DENG
Journal of Biomedical Engineering 2013;30(3):588-591
The study was aimed to assess the effect of Klotho gene and sinoatrial node pacing channel gene (HCN4 and HCN2) for studying sick sinus syndrome, with Klotho gene under the interference of Plasmid-mediated short hairpin RNA. Twenty-five C57BL/6J mice were divided into four groups, i. e, plasmid shRNA 24h group, plasmid shRNA 12h group, sodium chloride 24h group and sodium chloride 12h group. Plasmid shRNA 50microL (1microg/microL) and sodium chloride 50microl were respectively injected according to mice vena caudalis into those in plasmid shRNA group and sodium chloride group. After 12h or 24h respectively, all mice were executed and their sinoatrial node tissues were cut. The mRNA of Klotho, HCN4 and HCN2 gene were detected by RT-PCR. The results of RT-PCR showed that Klotho, HCN4 and HCN2 mRNA levels were lower compared with those in sodium chloride 12h group after 12h interference interval. The results indicated that there might be the a certain relationship between Klotho gene and sinoatrial node pacing channel gene.
Animals
;
Glucuronidase
;
genetics
;
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
;
genetics
;
metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Plasmids
;
genetics
;
Potassium Channels
;
genetics
;
metabolism
;
RNA Interference
;
RNA, Messenger
;
genetics
;
metabolism
;
RNA, Small Interfering
;
genetics
;
Sinoatrial Node
;
metabolism
;
physiology
;
physiopathology