Protective Effects of 3,4-Seco-Lupane Triterpenes from Food Raw Materials of the Leaves of Eleutherococcus Senticosus and Eleutherococcus Sessiliflorus on Arrhythmia Induced by Barium Chloride.

As a traditional wild vegetable and food raw material, the leaves of Eleutherococcus senticosus and Eleutherococcus sessiliflorus are rich in 3,4-seco-lupane triterpenes, including chiisanoside (CSS), divaroside (DVS), sessiloside-A (SSA), and chiisanogenin (CSG). This study was conducted to evaluate the anti-arrhythmic effects of these 3,4-seco-lupane triterpenes. Evaluation of the cytotoxicity of compounds was performed by measuring cell viability and apoptosis with the CCK-8 assay. In vivo, arrhythmia was induced by rapid injection of BaCl2 via rat caudal vein. The occurrence time and duration of arrhythmias in rats were studied. The levels of SOD and MDA in serum, and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase in myocardial homogenate were detected by ELISA. The histopathological changes of rats myocardial were observed by HE staining. Changes in the expression of PKA and related proteins were detected by Western blot. The 3,4-seco-lupane triterpenes interactions with protein kinase A were analyzed by molecular docking. In the present study, we found that 3,4-seco-lupane triterpenes exhibited powerful anti-arrhythmic activity, especially DVS completely relieved the ventricular arrhythmia induced by BaCl2 . This study suggests that the leaves of E. senticosus and E. sessiliflorus might be used as functional food materials to prevent arrhythmia, and DVS can potentially be further developed as an anti-arrhythmic drug.

Arnebiae Radix prevents atrial fibrillation in rats by ameliorating atrial remodeling and cardiac function.

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebiae Radix, a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. AIM OF THE STUDY: The combination of acetylcholine (Ach) and CaCl2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl2 induced AF compared to amiodarone, which was employed as the positive control. MATERIALS AND METHODS: To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl2 (60 µg/mL Ach and 10 mg/mL CaCl2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. RESULTS: In Ach-CaCl2-induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix-treated group. CONCLUSIONS: Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl2-induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future.

Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.

INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

New diterpenoid alkaloids from Aconitum coreanum and their anti-arrhythmic effects on cardiac sodium current.

Two new diterpenoid alkaloids, Guan-Fu base J (GFJ, 1) and Guan-Fu base N (GFN, 2) along with nineteen known alkaloids (3-21) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics, which is the raw material of a new approval anti-arrhythmia drug "Acehytisine Hydrochloride". The structures of isolated compounds were established by means of 1D, 2D NMR spectroscopic and chemical methods. All isolates obtained in the present study were evaluated for their inhibitory effects on blocking the ventricular specific sodium current using a whole-cell patch voltage-clamp technique. Among these 21 compounds, Guan-Fu base S (GFS, 3) showed the strongest inhibitory effect with an IC50 value of 3.48 µM, and only hetisine-type C20 diterpenoid alkaloids showed promising IC50 values for further development.

Prophylactic and therapeutic effects of garlic extract on Nerium oleander-induced arrhythmia: a new approach to antiarrhythmic therapy in an ovine model.

CONTEXT: Oleander is a potent cardiotoxic plant and is a common cause of poisoning in human and animals. There is no affordable and cost-effective treatment for oleander poisoning. Objective. To evaluate the prophylactic and therapeutic effects of garlic extract (Allium sativum) on Nerium oleander (a potent cardiotoxic plant) intoxication in sheep. MATERIALS AND METHODS: Eight sheep were intravenously infused with an unsterilized hydro-ethanol extract of garlic (50 mg/kg) before or after receiving a lethal dose of dried leaves (as a powder) of oleander (100 mg/kg, orally). The cardiac rhythm was continuously monitored using biopotential wireless transmitters and telemetry system. For evaluation of therapeutic effects, six sheep received the lethal dose of oleander and were administered with garlic extract after development of cardiac arrhythmias. Subsequently, the survived animals from the therapeutic study (four sheep) were administered with oleander without receiving any medication. Some blood constituents, including total antioxidant capacity, malondialdehyde, and troponin I, were compared between treated and untreated animals. RESULTS: Pretreatment with garlic extract reversed the arrhythmia caused by oleander to its previous normal rhythm in seven sheep, but, one sheep died of ventricular fibrillation. On therapeutic treatment, four sheep survived while two died of ventricular fibrillation. Dosing with oleander without receiving garlic extract resulted in death of all sheep due to ventricular fibrillation. Blood constituents did not show any significant changes between treated and untreated sheep, and before and after intoxication. CONCLUSIONS: Garlic extract reduced the case fatality from 100% to 12.5% and 33.3% as a prophylactic or therapeutic agent, respectively. Additionally, garlic extract delayed the time of onset of arrhythmias and prolonged the interval between intoxication and death of the animals. Garlic extract could be considered to be a potential and affordable antidote in oleander poisoning. However additional studies with a larger sample size and in other species need to be performed to confirm the results in this study.

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: a potential anti-arrhythmic agent.

CONTEXT: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations. OBJECTIVE: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat. MATERIALS AND METHODS: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery. RESULTS: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p < 0.05). Ventricular tachycardia (VT)/VF numbers (3.2 ± 1.2), durations (4.9 ± 2.6) and also arrhythmia severity (1.9 ± 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 ± 11.6, 52 ± 31 and 3.3 ± 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p < 0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval. CONCLUSION: The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.

A new triterpene and an antiarrhythmic liriodendrin from Pittosporum brevicalyx.

A new triterpene, 21-O-senecioyl-R(1)-barrigenol (1) and 13 known compounds were isolated from the ethanol extracts of the leaves and bark of Pittosporum brevicalyx (Oliv.) Gagnep. Their structures were elucidated based on spectral data. The antiarrhythmic action of one furofuran lignan, liriodendrin (2), was tested on a model of CaCl(2)-induced arrhythmia and compared with the effect of verapamil. The prophylactic administration of liriodendrin (2) was effective in prolonging latency of arrhythmia and reducing the occurrence of ventricular fibrillation from 75% to 25%. The overall mortality rate was significantly reduced by the prophylactic administration of liriodendrin from 87.5% to 25%. The antiarrhythmic effect of liriodendrin (5.0 mg/kg) was similar to that of verapamil (1.05 mg/kg). Thus, liriodendrin may be a potent suppressor of CaCl(2)-induced arrhythmias.

Daurisoline suppressed early afterdepolarizations and inhibited L-type calcium current.

Our previous studies have shown that daurisoline (DS) exerted antiarrhythmic effects on various experimental arrhythmias. In this study, the effects of DS on early afterdepolarizations (EADs) and its possible mechanisms have been investigated. Cardiac hypertrophy was induced in rabbits by coarctating the abdominal aorta. The effects of DS on action potential duration (APD) and the incidences of EADs were studied in hypertrophied papillary muscles of rabbits in the conditions of low external K(+) concentration ([K(+)]o) and dofetilide (dof) by using standard microelectrode technique. The whole-cell patch clamp was used to record the L-type calcium current (I(Ca-L)) in isolated left ventricular cells of rabbits. The results showed that in hypertrophied papillary muscles of rabbits with low [K(+)]o ([K(+)]o = 2.7 mM), 1 microM dof prolonged APD(50) and APD(90) markedly and the incidence of EADs was 66.7% (4/6, p < 0.01); when 15 microM DS was applied, the incidence of EADs was 0% (0/4, p < 0.01) and the prolonged APD was shortened (p < 0.01). In a single myocyte, DS could also inhibit EADs induced by dof, low [K(+)]o and low external Mg(2+) concentration ([Mg(2+)]o) ([Mg(2+)](o) = 0.5 mM). DS could decrease the triangulation. In a single myocyte, DS could make the I-V curve upward, shift the steady-state activation curves to the right and the steady-state inactivation curves to the left and prolong the tau value of recovery curve obviously. These results suggested that DS could inhibit EADs which may be associated with its blockade effects on I(Ca-L).

[HPLC fingerprint of the antiarrhythmic fraction of Valeriana officinalis].

OBJECTIVE: To establish HPLC fingerprints of the Antiarrhythmic fraction of Valeriana officinalis. METHODS: Agilent C18 (250 mm x 4.6 mm, 5 microm) column was used and the acetonitrile-water was chosen as the mobile phase in a gradient mode. The column temperature was 380 degrees C and the detection wavelength was 218 nm. The detection time was 70 min, and the flow rate was 1.0 mL/ min. RESULTS: Fifteen characteristic peaks were indicated in HPLC fingerprints. The relative retention time and the ranges of relative areas of the common peaks were also determined. CONCLUSION: This method is simple and accurate with a good reproducibility and provides a reference standard for the quality control of Valeriana officinalis.

[Antiarrhythmic effect of ethyl acetate extract from Chrysanthemum Morifolium Ramat on rats].

OBJECTIVE: To investigate the effect of ethyl acetate extract from Chrysanthemum Morifolium Ramat (CME) on experimental arrhythmia induced by ischemia/reperfusion or aconitine in rats and to explore its underlying mechanisms. METHODS: Arrhythmia model in intact rat was induced by aconitine (30 microg/kg body weight, i.v.). In isolated Langendorff perfused rat hearts, regional ischemia and reperfusion was induced by ligation and release of left anterior descending artery. The ventricular fibrillation threshold (VFT), effective refractory period (ERP), and diastolic excitation threshold (DET) in the isolated heart were measured. The action potentials of papillary muscle in rat right ventricle were recorded by conventional glass microelectrode technique. RESULTS: Compared with control group CME significantly decreased the number and duration of ventricular tachycardia (VT); delayed the occurrence of ventricular premature beats (VPB) and VT induced by aconitine. Arrhythmia score of the CME group was lower than that in aconitine-treated group. CME markedly prolonged the ERP and increased the VFT in the isolated perfused rat hearts during ischemia and reperfusion. CME prolonged action potential duration at 50% and 90% repolarization of the right ventricular papillary muscles and decreased the maximal rate of rise of the action potential upstroke, but did not affect the resting potential, amplitude of action potential. CONCLUSION: CME can reduce myocardial vulnerability and exerts its antiarrhythmic effects induced by aconitine or ischemia/reperfusion, which may be related to its prolongation of action potential duration and effective refractory period that enhance the electrophysiological stability of myocardiaium.

The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells.

Developing effective drug therapies for arrhythmic diseases is hampered by the fact that the same drug can work well in some individuals but not in others. Human induced pluripotent stem (iPS) cells have been vetted as useful tools for drug screening. However, cardioactive drugs have not been shown to have the same effects on iPS cell-derived human cardiomyocytes as on embryonic stem (ES) cell-derived cardiomyocytes or human cardiomyocytes in a clinical setting. Here we show that current cardioactive drugs affect the beating frequency and contractility of iPS cell-derived cardiomyocytes in much the same way as they do ES cell-derived cardiomyocytes, and the results were compatible with empirical results in the clinic. Thus, human iPS cells could become an attractive tool to investigate the effects of cardioactive drugs at the individual level and to screen for individually tailored drugs against cardiac arrhythmic diseases.

Model systems for the discovery and development of antiarrhythmic drugs.

Cardiovascular diseases are the leading cause of mortality worldwide and about 25% of cardiovascular deaths are due to disturbances in cardiac rhythm or "arrhythmias". Arrhythmias were traditionally treated with antiarrhythmic drugs, but increasing awareness of the risks of presently available antiarrhythmic agents has greatly limited their usefulness. Most common treatment algorithms still involve small molecule drugs, and antiarrhythmic agents with improved efficacy and safety are sorely needed. This paper reviews the model systems that are available for discovery and development of new antiarrhythmic drugs. We begin with a presentation of screening methods used to identify specific channel-interacting agents, with a particular emphasis on high-throughput screens. Traditional manual electrophysiological methods, automated electrophysiology, fluorescent dye methods, flux assays and radioligand binding assays are reviewed. We then discuss a variety of relevant arrhythmia models. Two models are widely used in testing for arrhythmogenic actions related to excess action potential prolongation, an important potential adverse effect of chemical entities affecting cardiac rhythm: the methoxamine-sensitized rabbit and the dog with chronic atrioventricular block. We then go on to review models used to assess potential antiarrhythmic actions. For ventricular arrhythmias, chemical induction methods, cardiac or neural electrical stimulation, ischaemic heart models and models of cardiac channelopathies can be used to identify effective antiarrhythmic agents. For atrial arrhythmias, potentially useful models include vagally-maintained atrial fibrillation, acute asphyxia with atrial burst-pacing, sterile pericarditis, Y-shaped atria surgical incisions, chronic atrial dilation models, atrial electrical remodelling due to sustained atrial tachycardia, heart failure-related atrial remodelling, and acute atrial ischaemia. It is hoped that the new technologies now available and the recently-developed models for arrhythmia-response assessment will permit the introduction of newer and more effective antiarrhythmic therapies in the near future.

[Effects of CASI on myocardial ischemia-reperfusion arrhythmia in rats].

OBJECTIVE: To observe the protective effect of compound acanthopanax senticosus injection (CASI) on myocardial ischemia-reperfusion arrhythmia in rats. METHOD: The myocardial ischemia-reperfusion model was induced by 30 min coronary occulusion and 60 min reperfusion in openchest anesthetized rats. The changes of arrhythmia with electrocardiogram lead II, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the contents of malondialdehyde (MDA) and Ca2+ in myocardium were determined. RESULT: In rats treated by CASI (in a dosage of 25, 50 and 100 mg x kg(-1) femoral vein infusion at 30 min after coronary occulusion), the incidence of myocardial ischemia-reperfusion ventricular arrhythmias, for instance the ventricular tachycardia (VT) and ventricular fibrillation (Vf), was effectively prevented, the appearing time of arrhythmia was delayed and the duration of arrhythmia was shortened, while the elevated ST segment lowered as well. At the same time, the contents of myocardial Ca2+ and MDA were decreased significantly as well as the activities of myocardial SOD and GSH-Px increased markedly. CONCLUSION: CASI is of protective effect on myocardial ischemia-reperfusion arrhythmia, which may be related to scavenging the oxygen free radicals and Ca2+ overload formed during reperfusion.

[Cardioprotective and antiarrhythmic properties of preparations from Leuzea carthamoides, Aralia mandshurica, and Eleutherococcus senticosus].

It is established that pretreatment with Leuzea carthamoides extract (LCE) (1 ml/kg per os during 8 days) prevents the development of stress-induced (6-hr painful-emotional stress) damage of the rat heart. A chronic administration of LCE (1 ml/kg per os during 8 days) increased the cardiac tolerance to the cardiotoxic action of D, L-isoproterenol and the arrhythmogenic action of epinephrine. Pretreatment with naloxone (2 mg/kg) completely eliminated the cardioprotective effect LCE and attenuated but not abolished the antiarrhythmic effect of the phytoadaptogen. A chronic administration of LCE elevated the level of beta-endorphin levels in the rat blood plasma. It is suggested that the cardioprotective effect of LCE is related to an increase in the level of opioid peptides, which produce stimulation of the opioid receptors. It is also established that preliminary chronic administration of Aralia mandshurica extract (AME) increases the cardiac resistance to the arrhythmogenic action of a 45-min coronary artery occlusion, but has no effect on the necrosis/risk area ratio. A pretreatment with Eleutherococcus senticosus extract (ESE) (1 ml/kg per os during 8 days) prevented the stress-induced damages of the rat heart. A chronic administration of ESE increased the cardiac tolerance to the cardiotoxic action of D, L-isoproterenol and the arrhythmogenic action of epinephrine. The pretreatment with naloxone (2 mg/kg) completely eliminated both the cardioprotective action and the antiarrhythmic effect of the phytoadaptogen. A chronic administration of ESE increased the beta-endorphin level in the rat blood plasma. It is suggested that the cardioprotective and antiarrhythmic effects of ESE is also related to an increase in the endogenous opioid peptide levels. A chronic administration of ESE had no effect on the arrhythmogenic effect of a 45-min coronary artery occlusion and did not change the necrosis/risk area ratio in rats.

[Study on effect of Tiaomaiyin injection on experimental arrhythmia].

OBJECTIVE: To study the effect of Tiaomaiyin injection on the experimental arrhythmia for analyzing its underlying mechanism in the treatment of cardiovascular disease. METHOD: Experimental animals anesthetized with 20% urethane (6 mL x kg(-1)) were evenly randomized into control group, positive control group, low-dose and high-dose Tiaomaiyin group. The rate of ventricular fibrillation (VF) chloroform-induced in mice, and the epoch of ventricular extrasystole (VE), ventricular tachycardia (VT),VF and cardiac arrest (CA), actonitine-induced in rats (1.0 microg x mL(-1) x min(-1)), and vabain-induced in guinea pigs (10 microg x mL(-1) x min(-1)), were detected respectively. The result loas converted into cumulative dosage of actonitine or vabain. In ischemia-reperfusion model in rats, the duration of arrhythmia and activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. RESULT: After venous injection of Tiaomaiyin, VF in mice was lower significantly (P < 0.01), VE, VT, VF in rats and VF in guinea pigs were lowered considerably (P <0.05). The duration of arrhythmia in ischemia-reperfusion model was reduced considerably (P < 0.05), and the activity of myocardial SOD was raised significantly (P <0.01). CONCLUSION: Tiaomaiyin shows the reduction of experimental arrhythmia and protect effect to ischemia-reperfusion injury of the heart, which indicates that the effect mechanism may have the relationship with inhabition of lipid peroxidation and damnification of the free radical.

[Comparing the actions of the three flavone ingredients in choerospondias axillaris on arrhythmias induced by aconitine].

OBJECTIVE: To compare the actions of the three flavone ingredients in choerospondias axillaris on arrhythmias Induced by aconitine. METHOD: Langendorff perfuse was applied in the experiment, the antiarrhythmic action was to study by using aconitine on the the isolated heart; The antiarrhythmic action of the three flavone ingredients in choerospondias axillaris was to study by using i.v. aconitine in rat to induce arrhythmias. RESULT: Compared with the NS group, sample 1 and sample 2 both significantly prolonged the beginning time of VF of isolated heart and increased the dosage of aconitine, sample 3 reduced the beginning time of VF of isolated heart and decreased the dosage of aconitine, sample 1 and sample 2 both greatly prolonged the beginning time of VE, VT, VF, HA; sample 3 greatly reduced the beginning time of VT,VF. The actions of the three samples were in a concentration-dependent way. CONCLUSION: Sample 1 and sample 2 both resisted the occurrence of arrhythmias induced by aconitine, sample 3 markedly promoted the occurrence of arrhythmias induced by aconitine.

[Effect of puerarin on L-type calcium channel in isolated rat ventricular myocytes].

OBJECTIVE: To observe the effect of Puerarin on L-type calcium channel in isolated rat ventricular myocytes. METHOD: The cardiac ventricular myocytes were isolated enzymatically by Langendorff perfusion techniques at constant flow rate. Whole-cell recording of patch-clamp techniques was used to observe the current of L-type calcium channel. RESULT: Puerarin 2.4 mmol x L(-1) could inhibit the current of L-type calcium channel of rat ventricular myocytes and this inhibition was time-dependent. Purerarin elevated the current-voltage (I-V) curve of calcium current. CONCLUSION: Puerarin can inhibit L-type calcium current of rat ventricular myocytes. Which implies that puerarin takes part in anti-myocardial ischemia and anti-arrhythmics partly due to the inhibition of L-type calcium channel.

Pharmacokinetic-pharmacodynamic modeling of daurisoline and dauricine in beagle dogs.

AIM: To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of daurisoline and dauricine, and compare their effects on cardiac electrophsiology, blood pressure, and hemodynamics in beagle dogs. METHODS: The plasma drug concentration was determined by the reversed-phase HPLC method and the effects on cardiac and hemodynamics were recorded by polygraph. The pharmacokinetic and PK-PD model parameters were calculated. RESULTS: The pharmacokinetics were best fitted to a two-compartment open model, and the relationship between effect and effect compartment concentration of both drugs could be represented by the sigmoid-E(max) model. There were no significant differences in main pharmacokinetics and PK-PD parameters between the two drugs. CONCLUSION: No statistically different kinetic disposition characteristics and potencies of inhibitory effects on myocardial function of daurisoline and dauricine were found in beagle dogs.

[Effect of tetradrine on electrophysilogic changes caused by rising of left ventricular preload in guinea pigs].

OBJECTIVE: To investigate the changes of guinea pig heart electrophysiological properties caused by increasing left ventricular preload, and to assess the effects of tetradrine on these changes. METHOD: Working model preparation of guinea pig hearts in vitro was used, and the preload of left ventricle was increased by adjusting the prefusion pressure of left atria. The changes of heart electrophysiologic parameters including monophasic action potential duration (MAPD90), monophasic action potential amplitude (MAPA), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) were observed before and after altering the preload of left ventricle, and compared in the absence and presence of tetradrine, streptomycin or verapamil. RESULT: The rising of left ventricular preload led to shortening of MAPD90, ERP, and to descent of MAPA, VFT (all P<0.01). Both Tetradrine and streptomycin inhibited these changes of heart electrophysiologic parameters caused by elevation of left ventricular afterload (all P<0.01). In contrast, verapamil had no effects on the preload-related electrophysiological changes (all P>0.05). CONCLUSION: Electrophysiologic changes caused by increasing left ventricular preload may be inhibited by tetrandrine, through inhibition of stretch-activated ion channels.