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

OBJECTIVETo observe the therapeutic effect of acupoint sticking of Wuzhuyu (Evodia Rutaecarpa) for treatment of bradycardia.

METHODSSixty cases were randomly divided into an observation group and a control group, 30 cases in each group. The observation group was treated with acupoint sticking of Wuzhugu (Evodia Rutaecarpa) at Neiguan (PC 6) and Xinshu (BL 15) once each day. The control group was treated with oral administration of Xinbao pills, 3 pills each time, thrice each day. The therapeutic effects and changes of 24 hours' holter were observed after 4 weeks.

RESULTSAfter treatment, 24 hours' average heart rate was significantly improved in the two groups, with significant differences as compared with those before treatment (both P<0.01) and with no significant difference between the two groups (P>0.05). The total effective rate was 86.7% (26/30) in the observation group and 83.3% (25/30) in the control group, their therapeutic effect being similar.

CONCLUSIONAcupoint sticking of Wuzhugu (Evodia Rutaecarpa) can significantly raise the levels of 24 hours' average heart rate in the patients of bradycardia. This therapy and Xinbao pills have similar therapeutic effect on the improvement of clinical symptom and heart rate levels.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Bradycardia ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

The purpose of this study was to investigate the feasibility of different fetal heart rate (FHR) ranges in the nonstress test (NST) and to better understand the meaning of mild bradycardia and/or tachycardia without non-reassuring patterns. We employed the heredity to show that mild bradycardia (100-119 beats per minute, bpm) and mild tachycardia (161-180 bpm) regressed to the normal FHR range (120-160 bpm). We used linear regression to analyze FHR data from FHR tracings recorded 10 min before (NST, as the predictor) and 10 min after vibroacoustic stimulation testing (as the dependent variable). Acceleration for 15 bpm-15 seconds (Acc1515) and deceleration for 15 bpm-15 seconds (Dec1515) in the NST were also analyzed for each group. The slope of the best-fit line was the largest in the mild bradycardia group and the smallest in the normal range group. Dec1515 was most prominent in mild tachycardia and both the mild bradycardia and tachycardia groups regressed towards the mean FHR range. Therefore, we propose that both mild bradycardia and tachycardia of FHR in non-acute situations (range between 100 and 180 bpm) are not regarded a pathologic signal for clinical use.
Acoustic Stimulation ; Bradycardia/physiopathology ; Female ; *Fetal Monitoring ; Heart Rate, Fetal/*physiology ; Humans ; Pregnancy ; Pregnancy Trimester, Third ; Regression Analysis ; Tachycardia/physiopathology

Time irreversibility is a fundamental property of nonequilibrium systems. It is significant to measure the trend of change of time irreversible index under different physiological and pathological state of electrocardiosignal. We analyzed and tested the heart rate variability (HRV) signals of the normal sinus rhythm, atrial contraction, sinus bradycardia in the MIT-BIH standard database using the multiscale time irreversiblity method. It was shown that the time irreversiblity index of the normal heart rhythm, atrial premature beats and bradycardia were in the decreasing trend. The results would be helpful to clinical diagnosis as a secondary means.
Arrhythmia, Sinus ; physiopathology ; Atrial Premature Complexes ; physiopathology ; Bradycardia ; physiopathology ; Electrocardiography ; methods ; Heart Rate ; physiology ; Humans ; Signal Processing, Computer-Assisted ; Time Factors

This study sought to disclose whether Hurst index can be used as a criterion for distinguishing sinus and atrial arrhythmia signals. Normal sinus rhythm beats, atrial premature contraction (APC) beats, and sinus bradycardia (SBR) signals, were taken from the MIT-BIH standard database. Hurst index method was used to distinguish the two kinds of arrhythmia. The results showed that the Hurst exponents of three kinds of signals were larger than 0.5, but they were in different value region. The data indicated that the long-term relevant character was the best for normal signal, better for sinus bradycardia, and the worst for atrial premature beats. So Hurst index is a useful identification criterion for distinguishing sinus and atrial arrhythmia signals.
Algorithms ; Arrhythmia, Sinus ; diagnosis ; physiopathology ; Atrial Premature Complexes ; diagnosis ; physiopathology ; Bradycardia ; diagnosis ; physiopathology ; Diagnosis, Differential ; Electrocardiography ; Humans ; Signal Processing, Computer-Assisted

BACKGROUNDThe molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment.

METHODSTwenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively. Gene expression profiling was conducted by gene expression chip, and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the results of gene expression chip. We used isobaric tags for elative and absolute quantitation and Western blotting to identify altered proteins after SXSM treatment.

RESULTSThere was a constant decrease in the mean heart rate (32%, from 238 ± 6 beats/min to 149 ± 12 beats/min) after six weeks in model compared with that in sham group. This effect was partially reversed by 4-week SXSM treatment. Complementary DNA microarray demonstrated that the increased acetylcholinesterase and reduced nicotinic receptor were take responsibility for the increased heart rate. In addition, proteins involved in calcium handling and signaling were affected by SXSM treatment. Real-time RT-PCR verified the results from gene chip. Results from proteomics demonstrated that SXSM enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle in ventricular myocardium to improve ATP generation.

CONCLUSIONSLong-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.

Animals ; Bradycardia ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Heart Rate ; drug effects ; Proteomics ; Rabbits ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction

AIMTo explore the neurological mechanism of heart rate slowing down after birth and to investigate if the heart itself participates in the process.

METHODSWith the method of HRV power spectrum analysis, the regulatory mechanisms of autonomic nerves over heart rate were studied on different age groups of human beings and rabbits. Similar experiments were carried out on isolated perfused rabbit hearts in order to study if the heart itself were involved in the process of heart rate slowing down as they grew up.

RESULTSThe ratio of parasympathetic tone to sympathetic one is significantly increased as a child or rabbit grows up while the heart rate becomes slower. The spontaneous beating of isolated rabbit heart also slows down as the rabbit becomes older.

CONCLUSIONBoth of the nerve factor and heart itself are involved in the process of slowing down of heart rate as a child grows up.

Aging ; physiology ; Animals ; Autonomic Nervous System ; physiology ; Bradycardia ; physiopathology ; Child ; Electrocardiography ; Heart Rate ; physiology ; Humans ; In Vitro Techniques ; Infant ; Infant, Newborn ; Rabbits ; Signal Processing, Computer-Assisted

Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant baroreflex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS.
Animals ; Arginine ; analogs & derivatives ; pharmacology ; Baroreflex ; Benzazepines ; pharmacology ; Blood Pressure ; Bradycardia ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Heart Rate ; Myocardial Contraction ; Neuropeptide Y ; blood ; Rats ; Receptors, Neuropeptide Y ; antagonists & inhibitors ; Streptozocin

PURPOSE: During carotid angioplasty and stenting (CAS), hemodynamic instability (HDI) can occur, possibly causing post-procedural ischemic complications. The goal of this study was to investigate the risk factors of HDI focusing on characteristics of plaque. MATERIALS AND METHODS: Thirty nine CAS patients were retrospectively evaluated for HDI. Prolonged HDI that lasted over 30 minutes was analyzed in relation to characteristics of calcified plaque. RESULTS: Nineteen (48.7%) patients had HDI. Ten of the 19 had both bradycardia and hypotension, and nine had only bradycardia. All bradycardia was treated well with a transcutaneous temporary cardiac pacemaker. But eight patients presented with prolonged hypotension in spite of recovery of bradycardia. Calcified plaque was a related factor associated with HDI (odds ratio, 8.571; 95% confidence interval, 1.321-55.62; p=0.024). Extensive and eccentric type calcified plaques were associated with prolonged hypotension (p=0.04, and p=0.028, respectively). CONCLUSION: The calcification of plaque is a predictable factor of HDI during CAS, and its extensive and eccentric calcified plaques may be related to prolonged HDI.
Aged ; Angioplasty/*adverse effects ; Bradycardia/complications ; Carotid Arteries/*surgery ; Carotid Stenosis/*physiopathology ; Female ; *Hemodynamics ; Humans ; Hypotension/complications ; Intraoperative Complications/*etiology/radiography ; Intraoperative Period ; Logistic Models ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Stents ; Tomography, X-Ray Computed

INTRODUCTIONAntimonial compounds are regarded as the treatment of choice for cutaneous leishmaniasis (CL). Systemic administration of these drugs has some side effects including cardio toxicity and electrocardiogram (EKG) changes. The objective of our study was to evaluate EKG changes in the patients with CL treated with systemic glucantime.

MATERIALS AND METHODSOne hundred and thirty-one patients were enrolled in this prospective study. All of the selected patients had confirmed CL and were candidates for treatment with systemic glucantime. The patients were treated with systemic glucantime and EKG was performed before, during (weekly) and 1 month after cessation of the treatment. All of the collected data were analysed using SPSS software.

RESULTSThe most common change was prolonged QT interval that was seen in 19% of the patients. ST depression occurred in 6.1% of the patients. Minimal ST elevation occurred in 3% and inverted T was observed in 7.4% of the patients. Single premature atrial contraction (PAC) and single premature ventricular contraction (PVC) occurred in 0.7% and 2.29% of patients, respectively. Bradycardia was observed in 10.6% and left bundle branch block in 0.7% of the patients. All of these changes reversed after stopping the treatment except 1 case with left bundle branch block that lasted for 1 month after the treatment.

CONCLUSIONSOur results showed that treatment with glucantime can induce many ECG changes as QT prolongation have significant risk. We suggest that ECG monitoring should be performed in high-risk patients undergoing glucantime treatment with special attention to ECG changes mostly prolonged QT interval.

Administration, Oral ; Adult ; Animals ; Antimony ; Antiprotozoal Agents ; administration & dosage ; adverse effects ; Atrial Premature Complexes ; chemically induced ; physiopathology ; Bradycardia ; chemically induced ; physiopathology ; Bundle-Branch Block ; chemically induced ; physiopathology ; Dose-Response Relationship, Drug ; Electrocardiography ; drug effects ; Female ; Follow-Up Studies ; Humans ; Leishmaniasis, Cutaneous ; complications ; drug therapy ; physiopathology ; Male ; Meglumine ; administration & dosage ; adverse effects ; Organometallic Compounds ; administration & dosage ; adverse effects ; Prognosis ; Prospective Studies ; Ventricular Premature Complexes ; chemically induced ; physiopathology