To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

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

It is proved that polydatin has cardioprotection against ischemia-induced arrhythmia, but the electrophysiological mechanism is not clear. The aim of the present study was to investigate the effect of polydatin on action potential (AP) in ventricular papillary muscle and the underlying ionic mechanism in rat using intracellular recording and whole-cell patch clamp techniques. The results showed: (1) In normal papillary muscles, polydatin (50 and 100 µmol/L) shortened duration of 50% repolarization (APD(50)) and duration of 90% repolarization (APD(90)) in a concentration-dependent manner (P<0.01). But polydatin had no effects on resting potential (RP), overshoot (OS), amplitude of action potential (APA) and maximal rate of depolarization in phase 0 (V(max)) in normal papillary muscles (P>0.05). (2) In partially depolarized papillary muscles, polydatin (50 µmol/L) not only shortened APD(50) and APD(90) (P<0.05), but also decreased OS, APA and V(max) (P<0.05). (3) After pretreatment with glibenclamide (10 µmol/L), an ATP-sensitive K(+) channel blocker, the electrophysiological effect of polydatin (50 µmol/L) was partially inhibited. (4) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the effect of polydatin (50 µmol/L) on AP. (5) Polydatin (25, 50, 75 and 100 µmol/L) decreased L-type Ca(2+) current in ventricular myocytes in a concentration-dependent manner (P<0.05). (6) Polydatin (50 µmol/L) increased ATP-sensitive K(+) current in ventricular myocytes (P<0.05). The results suggest that polydatin can shorten the repolarization of AP in normal papillary muscle and inhibit AP in partially depolarized papillary muscle, which might be related to the blocking of L-type Ca(2+) channel and the opening of ATP-sensitive K(+) channel.
Action Potentials ; drug effects ; Animals ; Calcium Channels, L-Type ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Heart Ventricles ; cytology ; KATP Channels ; metabolism ; Male ; Papillary Muscles ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology

OBJECTIVETo study the effect of Ginkgo biloba extract 50 (GBE50), a new multicomponent drug with a polyvalent action extracted from the leave of Ginkgo biloba, on the action potentials in normal and simulated ischemic guinea pig papillary muscles.

METHODStandard intracellular microelectrode technique was used to examine the effects of GBE50 on the action potential parameters [action potential amplitude (APA), overshoot, rest potential, action potential amplitude at 20%, 50%, 90% of repolarization (APD20, APD50, APD90)].

RESULTIn normal guinea pig cardiac papillary muscles, GBE50 (20, 50, 100 mg x L(-1)) shortened APD50 and APD90, and did not affect the rest potential parameters. In simulated ischemic guinea pig cardiac papillary cells, action potential duration was significantly shortened, resting potential and action potential amplitude were reduced. 100 mg x L(-1) GBE50 partly attenuated the change induced by ischemia.

CONCLUSIONGBE50 shortened APD of normal guinea pig cardiac papillary cells in a concentration-dependent manner. Under ischemia, all action potential parameters were reduced . GBES0 could alleviate the electrophysiological heterogeneity of ischemic myocardium, which may attenuate myocardial ischemia and block the onset of arrhythmia.

Action Potentials ; drug effects ; Animals ; Disease Models, Animal ; Ginkgo biloba ; chemistry ; Guinea Pigs ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; physiopathology ; Papillary Muscles ; drug effects ; physiology ; physiopathology ; Plant Extracts ; administration & dosage ; Random Allocation

OBJECTIVETo investigate the effects and underlying mechanisms of interferon-alpha (IFN-alpha) on the isolated Langendorff perfused rat hearts and the isolated papillary muscles.

METHODSThe left ventricular developed pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/-dP/dt(max)), left ventricular end-diastolic pressure (LVEDP), heart rate (HR) and coronary flow (CF) were recorded in isolated Langendorff perfused rat hearts. The average contractile force was measured in the isolated papillary muscles of rat right ventricle.

RESULTIFN-alpha (10 - 10,000 U/ml) induced a concentration-dependent decrease of LVDP and +/-dP/dt(max), and increase of LVEDP and CF in the isolated perfused rat heart (P < 0.05), and decrease of the average contractile force of the papillary muscle (P <0.05). Pretreatment with L-NAME (10(-4) mol/L), an inhibitor of nitric oxide synthase, attenuated the effect of IFN-alpha in the isolated rat hearts and the isolated papillary muscles (P <0.05). Isoproterenol (ISO, 10(-9) - 10(-6)mol/L) increased the contractile force of the rat papillary muscles in a concentration-dependent manner. Perfusion for 10 min with IFN-alpha at 1,000 U/ml attenuated the enhancing effect of ISO. Pretreatment with L-NAME reduced the effects of IFN-alpha on the isolated papillary muscles.

CONCLUSIONIFN-alpha may induce a negative inotropic effect in normal and beta-adrenergic activated cardiac muscles and this effect at least partly be mediated by nitric oxide.

Animals ; Heart ; drug effects ; physiology ; Heart Rate ; drug effects ; In Vitro Techniques ; Interferon-alpha ; pharmacology ; Male ; Myocardial Contraction ; drug effects ; Myocardium ; metabolism ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Papillary Muscles ; drug effects ; metabolism ; physiology ; Perfusion ; Rats ; Rats, Sprague-Dawley

Action Potentials ; drug effects ; Animals ; Estradiol ; pharmacology ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Myocardial Contraction ; drug effects ; Papillary Muscles ; drug effects ; physiology ; Progesterone ; pharmacology

The purpose of this study was to investigate the effects of resveratrol on delayed afterdepolarization (DAD) and triggered activity (TA) induced by ouabain in guinea pig papillary muscles and the underlying mechanism. Action potentials were recorded using intracellular microelectrode technique. The results obtained are as follows: (1) DAD and TA induced by ouabain (1 micromol/L) were inhibited by pretreatment with resveratrol (30, 60, and 120 micromol/L) in a concentration-dependent manner; (2) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the above effect of resveratrol (60 micromol/L ); (3) 5 micromol/L 17beta-estradiol (E(2)) or 30 micromol/L resveratrol had no effects on DAD and TA, however, resveratrol combined with E(2) at the same doses exerted significant inhibitory effects on DAD and TA; (4) Pretreatment with tamoxifen (TAM, 10 micromol/L), an inhibitor of estrogen receptor, also did not blocked the effects of resveratrol (60 micromol/L) on DAD and TA induced by ouabain. All these results indicated that resveratrol exerted an inhibitory effects on DAD and TA induced by ouabain, possibly by reducing calcium influx, which might not be mediated by NO and estrogen receptor. The antiarrhythmic effects of resveratrol may contribute to its cardioprotective action.
Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Calcium Channel Blockers ; pharmacology ; Dose-Response Relationship, Drug ; Guinea Pigs ; Male ; Microelectrodes ; Ouabain ; antagonists & inhibitors ; Papillary Muscles ; physiology ; Stilbenes ; pharmacology

OBJECTIVETo explore the possible mechanism of cyclovirobuxine D (CVB-D) in countering and inducing arrhythmia, by way of studying its electro-physiological effect on ventricular papillary muscles of rats in vitro.

METHODSThe transmembrane potential of rat's isolated right ventricular papillary muscles were recorded using conventional glass micro-electrode technique.

RESULTS(1) CVB-D in concentration of 13.3-63.3 micromol/L, showed prolonging effect on the action potential repolarization time, mainly the action potential duration 50 (APD50), APD70 and APD90, in dose-dependent manner, in concentration of 33.3-63.3 micromol/L, it could inhibit the resting potential, action potential amplitude (APA) and maximum depolarization velocity (Vmax) in dose-dependent manner. (2) CVB-D also showed time-dependent effect, the effect initiated 10 min after 20 micromol/L was perfused in ventricular muscle, the APD50, APD70 and APD90 were potentiated gradually along with prolongation of action time and reached the peak at 30-40 min, without any potentiation thereafter. (3) CVB-D could markedly prolong the effective refractory period (ERP) of action potential, increase the ratio of ERP/APD. (4) CVB-D in concentration of 33.3 micromol/L could induce frequent, multifocal spontaneous arrhythmia in some cells when the action time was longer than 45 min.

CONCLUSIONCVB-D has the action of anti-ventricular arrhythmia, the mechanism is correlated with the prolongation of APD and ERP of ventricular muscle as well as the increase of ERP/APD ratio, while it also has the effect of inducing arrhythmia, the mechanism might be concerned with excessive prolongation of APD and the inhibition on RP, APA and Vmax.

Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Electrophysiologic Techniques, Cardiac ; Heart Ventricles ; drug effects ; In Vitro Techniques ; Male ; Myocytes, Cardiac ; cytology ; Papillary Muscles ; drug effects ; Rats ; Rats, Sprague-Dawley ; Refractory Period, Electrophysiological ; drug effects ; Ventricular Function

The purpose of this study was to investigate the electrophysiological effects of resveratrol on guinea pig papillary muscles and the underlying mechanism. Action potentials were recorded by using intracellular microelectrode technique. The results obtained are as follows: (1) In normal papillary muscles, resveratrol (30, 60, and 120 micromol/L) shortened the duration of action potential (APD) in a concentration-dependent manner. (2) In partially depolarized papillary muscles, resveratrol (60 micromol/L ) not only shortened APD, but also decreased the amplitude of action potential (APA), overshoot (OS) and maximal rate of depolarization in phase 0 (Vmax). (3) Perfusion with Ca2+-free K-H solution, completely abolished the effects of resveratrol (60 micromol/L) on papillary muscles. (4) Application of potassium channel blocker tetraethylammonium chloride (TEA, 20 mmol/L) did not prevent the effect of resveratrol (60 micromol/L) on action potential. (5) Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the effect of resveratrol (60 micromol/L). All these results indicate that the electrophysiological effects of resveratrol on guinea pig papillary muscles are likely due to the reduction of calcium influx, which might not be mediated by NO.
Action Potentials ; drug effects ; Animals ; Calcium Channel Blockers ; pharmacology ; Guinea Pigs ; In Vitro Techniques ; Male ; Microelectrodes ; Papillary Muscles ; drug effects ; physiology ; Stilbenes ; pharmacology

To study the inotropic effect of enhanced Na(+)-Ca(2+) exchange in the rat papillary muscles and isolated heart, the developed tension in the rat papillary muscles was measured and the left ventricular functions were assessed in the isolated rat heart. E-4031, a selective activator for Na(+)-Ca(2+) exchange in rats, concentration-dependently increased the developed contractile tension in the rat papillary muscles (P<0.05, n=6) and the left ventricular functions in the isolated heart; KB-R7943, a selective Na(+)-Ca(2+) exchange inhibitor, exhibited opposite effect. A combination of 0.5 micromol/L ouabain and 3.0 micromol/L E-4031 resulted in a potentiation of the developed contractile tension of the rat papillary muscles from 0.25+/-0.03 g to 0.29+/-0.04 g. The combination also enhanced the augmentation of the left ventricular functions induced by ouabain. These results indicate that E-4031 exerts a positive inotropic effect on the rat papillary muscles and isolated heart via increasing the activity of Na(+)-Ca(2+) exchange, and potentiates the positive inotropic effects of ouabain.
Animals ; Cardiotonic Agents ; pharmacology ; Female ; Heart Ventricles ; cytology ; In Vitro Techniques ; Male ; Membrane Potentials ; drug effects ; Myocardial Contraction ; physiology ; Myocytes, Cardiac ; metabolism ; Ouabain ; pharmacology ; Papillary Muscles ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Sodium Channels ; metabolism ; Sodium-Calcium Exchanger ; physiology