Chronic Disease ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Heart ; drug effects ; physiopathology ; Heart Failure ; drug therapy ; physiopathology ; Humans ; Kidney ; drug effects ; physiopathology

OBJECTIVEOn the basis that pinacidil can produce an "all or none" repolarization in right ventricular wall of canine, to observe the effects of quinidine on the marked transmural dispersion of repolarization. Recent studies have shown that ventricular myocardium is composed of at least 3 electrophysiological distinct cell types: epicardial, endocardial, and midcardial cells. Differences in the response of the 3 cell types to pharmacologic agents and/or pathophysiological states often result in amplification of intrinsic electrical heterogeneities, thus providing a substrate as well as a trigger for the development of arrhythmias. The study was designed to observe the right ventricular transmural heterogeneity in vitro canine heart tissue preparation level.

METHODSThe strips were isolated from the anterior wall of the right ventricular of canine. The preparations perfused with oxygenated (95%O(2)/5%CO(2)) Tyrode's solution. The tissues were stimulated at basic cycle lengths of 1000 ms. Standard microelectrode techniques were used. Transmembrane action potentials were recorded from epicardial, midcardial and endocardial cells respectively from right ventricular free wall of canine on different conditions [perusing with Tyrode's solution (Control), pinacidil (2.5 micromol/L), and quinidine (5 micromol/L) in turn].

RESULTSCompared with that of endocardial cells, the action potentials of canine ventricular epicardial and midcardial cells had more obvious spike and dome morphology. Pinacidil (2.5 micromol/L) caused a loss of the dome of transmembrane action potentials and a marked abbreviation of the action potential duration (APD) in right ventricular epicardial and midcardial cells, especially in epicardial cells, but not in endocardial cells (n = 10). With pinacidil (2.5 micromol/L), in epicardial cells, phase 2 amplitude of action potentials decreased from (117.7 +/- 9.3) mV to (71.3 +/- 6.4) mV (P < 0.01), and 90% of the APD(90) decreased from (198.2 +/- 20.8) ms to (103.9 +/- 13.5) ms (P < 0.01). The transmural dispersion of action potential duration increased from (48.5 +/- 9.2) ms to (128.7 +/- 13.5) ms (P < 0.01). Quinidine (5 micromol/L) effectively prolonged the APD abbreviated by pinacidil, restored or partly restored the dome of transmembrane action potentials of epicardial and midcardial cells but not of endocardial cells (n = 10). In epicardial cells phase 2 amplitude increased from (71.3 +/- 6.4) mV to (106.6 +/- 7.7) mV (P < 0.01), and 90% of the APD(90) increased from (103.9 +/- 13.5) ms to (185.9 +/- 15.7) ms (P < 0.01). The transmural dispersion of action potential duration significantly decreased from (128.7 +/- 13.5) ms to (54.3 +/- 10.8) ms (P < 0.01). Quinidine reduced pinacidil-induced transmural dispersion of phase 2 amplitude and the APD in right ventricular wall of canine.

CONCLUSIONBy restoring the dome and the APD of the epicardial and midcardial cells action potentials, quinidine (5 micromol/L) could reduce the marked transmural dispersion of repolarization caused by pinacidil.

Action Potentials ; drug effects ; Animals ; Dogs ; Heart Ventricles ; drug effects ; physiopathology ; Pinacidil ; pharmacology ; Quinidine ; pharmacology

OBJECTIVETo determine effects of activating protein kinase C (PKC) on ventricular action potential duration restitution (APDR) and Burst stimulus induced arrhythmia in Langendorff-perfused rabbit hearts.

METHODSMale rabbits were equally divided into three groups randomly: control group (Tyrode's solution perfusion), PKC agonist phorbol-12-myristate-13-acetate (PMA, 100 nmol/L) group and PKC inhibitor bisindolylmaleimide (BIM, 500 nmol/L) group. Thirty minutes after perfusion, the monophasic action potential (MAP) and effective refractory period (ERP) were determined in right basal ventricle (RB), right apex (RA), left basal ventricle (LB) and left apex (LA) of all the animals, and APDR curve was drawn. Burst stimulus method was used to induce ventricular arrhythmia in perfused rabbit hearts; Real-time PCR was used to detect the mRNA expression of PKC in four different areas of ventricle.

RESULTSCompared with the control group, the ERP, 90% of monophasic action potential duration (MAPD(90)) and ERP/MAPD(90) were significantly shortened (all P < 0.01), the max slopes (S(max)) of APDR curve were significantly steeper (RB: 1.22 ± 0.23 vs. 0.65 ± 0.19; RA: 2.99 ± 0.29 vs. 1.02 ± 0.18; LB: 1.84 ± 0.21 vs. 0.85 ± 0.12; LA: 4.02 ± 0.32 vs.1.12 ± 0.23, all P < 0.01) and the incidences of ventricular arrhythmia were significantly increased in the PMA group. All parameters were similar between the BIM group and the control group (all P > 0.05).

CONCLUSIONActivating PKC could enhance the max slopes of APDR curve at various ventricular areas and subsequently increase arrhythmia susceptibility in Langendorff-perfused rabbit hearts.

Action Potentials ; Animals ; Arrhythmias, Cardiac ; physiopathology ; Heart ; drug effects ; physiopathology ; Male ; Protein Kinase C ; pharmacology ; Rabbits

OBJECTIVETo explore the effects of particulate matters less than 2.5 μm in aerodynamic diameter (PM2.5) on heart repolarization/depolarization and heart rate variability (HRV).

METHODSWe conducted a panel study for elderly subjects with heart disease in Beijing from 2007 to 2008. PM2.5 was measured at a fixed station for 20 h continuously each day while electrocardiogram (ECG) indexes of 42 subjects were also recorded repeatedly. Meteorological data was obtained from the China Meteorological Data Sharing Service System. A mixed linear regression model was used to estimate the associations between PM2.5 and the ECG indexes. The model was adjusted for age, body mass index, sex, day of the week and meteorology.

RESULTSSignificant adverse effects of PM2.5 on ECG indexes reflecting HRV were observed statistically and the strongest effect of PM2.5 on HRV was on lag 1 day in our study. However, there were no associations between PM2.5 and ECG indexes reflecting heart repolarization/depolarization. Additionally, the effects of PM2.5 on subjects with hypertension were larger than on the subjects without hypertension.

CONCLUSIONThis study showed ambient PM2.5 could affect cardiac autonomic function of the elderly people with heart disease, and subjects with hypertension appeared to be more susceptive to the autonomic dysfunction induced by PM2.5.

Aged ; Air Pollutants ; toxicity ; Electrocardiography ; Environmental Monitoring ; Female ; Heart Diseases ; physiopathology ; Heart Rate ; drug effects ; Heart Ventricles ; drug effects ; physiopathology ; Humans ; Male ; Middle Aged ; Particle Size

Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development.
Animals ; Cardiotonic Agents ; chemistry ; pharmacology ; Energy Metabolism ; drug effects ; Heart ; drug effects ; physiopathology ; Humans ; Myocardial Contraction ; drug effects ; Panax ; chemistry

OBJECTIVEAlthough after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise.

METHODSThirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo.

RESULTSSotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo.

CONCLUSIONSThese results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.

Adult ; Exercise ; physiology ; Exercise Test ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; physiology ; Humans ; Male ; Sotalol ; pharmacology

BACKGROUNDRenin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure (CHF) and atrial fibrillation (AF). This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing.

METHODSTwenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg x kg(-1) x d(-1) was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period (AERP), AERP dispersion (AERPd), intra- and inter-atrium conduction time (CT) and intra-atrium conduction velocity (CV) were determined. The inducibility and duration of AF were also measured in all groups. Finally, atrial fibrosis was quantified with Masson staining.

RESULTSAERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis (r = -0.74, P < 0.05). Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction (P < 0.05). Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd (P < 0.05), shortened intra- and inter-atrium conduction time (P < 0.05), and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF (P < 0.05), as well as atrial fibrosis (P < 0.01) induced by chronic rapid ventricular pacing.

CONCLUSIONSpironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics.

Animals ; Atrial Fibrillation ; prevention & control ; Cardiac Volume ; Collagen ; analysis ; Dogs ; Heart Atria ; drug effects ; pathology ; physiopathology ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Hemodynamics ; drug effects ; Spironolactone ; therapeutic use

OBJECTIVE: To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. METHODS: Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. RESULTS: There was a significant difference in CTFC between groups (P<0.05). The average CTFC values of the vessels with slow blood flow in CSF patients were, respectively, 49.98 ± 10.01 and 40.42 ± 11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values (frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00 ± 13.32 and 41.80 ± 15.38, 59.00 ± 4.69 and 50.00 ± 9.04, and 51.90 ± 8.40 and 40.09 ± 10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow flow before treatment were significantly decreased after treatment (P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP (all P>0.05). CONCLUSIONS The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.
Blood Pressure ; drug effects ; Coronary Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; No-Reflow Phenomenon ; drug therapy ; physiopathology

OBJECTIVETo study the effect of the Chinese medicine Qiangxin Fumai Granule (, QFG) on electrophysiological functions of the sinoatrial node during ischemia-reperfusion (IR) of the right coronary artery in rabbits.

METHODSThe right coronary artery IR model in rabbits was adopted. The modeled rabbits were randomly divided into 4 groups: the model group, the atropine group, the high-dose QFG group, and the low-dose QFG group, with 8 animals in each group. In addition, twelve rabbits were selected for the sham-operative group. The drugs were administered once via duodenal perfusion after modeling had been stabilized for 10 min. The changes in AA interval, the sinoatrial conduction time (SACT), the sinus node recovery time (SNRT), the corrected sinus node recovery time (CSNRT) and the index of sinus node recovery time (ISNRT) at different time points during ischemia and reperfusion were measured.

RESULTSThe AA interval was prolonged for more than 40 ms in the model group during ischemia. Compared with the model group, the four electrophysiological parameters abovementioned in the high-dose QFG group and the low-dose QFG group were decreased to different extents at each time point (P<0.01 or P<0.05), and no statistically significant differences were found between the QFG groups and the atropine group (P>0.05).

CONCLUSIONQFG is beneficial for accelerating the recovery of sinus node autorhythmicity and conduction function, so as to protect electrophysiological functions of the sinoatrial node. Accelerating the recovery of autorhythmicity and conduction function in the sinus node is considered its electrophysiological mechanism in the treatment of sinoatrial node injury induced by ischemia.

Animals ; Coronary Vessels ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electrophysiological Phenomena ; drug effects ; Heart Conduction System ; drug effects ; Myocardial Reperfusion Injury ; drug therapy ; physiopathology ; Phytotherapy ; Rabbits ; Sinoatrial Node ; drug effects ; physiopathology ; Time Factors

This study is to evaluate the effects of Shenmai injection on the temporal alterations of action potential (AP), early afterdepolarization (EAD) and delayed afterdepolarization (DAD) in papillary muscles. The action potentials were recorded by a glass electrode. APD at 90% repolarization (APD9 ) was measured, and spontaneous EAD and DAD were observed. The results show APD90 was significantly prolonged in model group compared with sham-operated group, whereas it was remained unchanged in Shenmai injec- tion treatment group and amiodarone group. The spontaneous EADs and DADs were frequently visible in model group. In conclusion, EAD, DAD and trigger activities increase gradually during pathological progression of rat cardiac hypertrophy, and Shenmai injection could improve the action potential change in rat cardiac hypertrophy.
Action Potentials ; drug effects ; Animals ; Blood Pressure ; drug effects ; Cardiomegaly ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Heart Ventricles ; drug effects ; physiopathology ; Injections ; Male ; Papillary Muscles ; drug effects ; physiopathology ; Rats ; Rats, Sprague-Dawley