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.

Effect of Lidocaine Injection of Ganglionated Plexi in a Canine Model and Patients With Persistent and Long-Standing Persistent Atrial Fibrillation.

Background This study assessed the effect of blockading neural transmission in the ganglionated plexi by injecting lidocaine into fat pads in the vagal nerve stimulation canine model and patients with persistent atrial fibrillation ( AF ). Methods and Results An efficacy test of lidocaine injection was performed in 7 canines. During vagal nerve stimulation, AF was sustained for >5 minutes. The lidocaine was injected into ganglionated plexi during sinus rhythm and reinduction of AF was attempted. Six patients with persistent AF were studied at open heart surgery. Lidocaine was injected into ganglionated plexi. Atrial electrograms were recorded from 96 epicardial electrodes covering Bachmann's bundle and atrial appendages. In the canine vagal nerve stimulation AF model, AF was not inducible in 4 of 7 after lidocaine injection. In patients with persistent AF , during baseline AF , there was a left atrium ( LA )-to-right atrium ( RA ) frequency gradient ( LA , mean cycle length [ CL ] 175±17 ms; RA , mean CL 192±17 ms; P<0.01). After lidocaine injection, AF persisted in all patients, and the LA -to- RA frequency gradient disappeared ( LA , mean CL 186±13 ms; RA , mean CL 199±23 ms; P=0.08). Comparison of mean CL s before and after lidocaine demonstrated prolongation of LA CL s ( P<0.05) with no effect on RA CL s. Conclusions In the canine vagal nerve stimulation AF model, lidocaine injection decreased inducibility of AF . In patients with persistent AF , atrial electrograms from the LA had shorter CL s than RA , indicating an LA -to- RA frequency gradient. Lidocaine injection significantly prolonged only LA CL s, explaining disappearance of the LA -to- RA frequency gradient. The mechanism of localized atrial electrogram CL prolongation in patients with persistent AF is uncertain.

Acute and Subacute Effects of Low Versus High Doses of Standardized Panax ginseng Extract on the Heart: An Experimental Study.

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Effects of Vitamin D on Blood Pressure, Arterial Stiffness, and Cardiac Function in Older People After 1 Year: BEST-D (Biochemical Efficacy and Safety Trial of Vitamin D).

BACKGROUND: The relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 µg), vitamin D 2000 IU (50 µg), or placebo daily. Primary outcomes were plasma concentrations of 25-hydroxy-vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N-terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25-hydroxy-vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N-terminal prohormone of brain natriuretic peptide concentration at 12 months. CONCLUSIONS: The absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011-005763-24a.

Incidence of left atrial abnormalities under treatment with dabigatran, rivaroxaban, and vitamin K antagonists.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown. METHODS: We studied 306 patients with AF (94 %) and AFL (6 %) undergoing transesophageal echocardiography. Patients received VKAs (n = 138), dabigatran (n = 68), or rivaroxaban (n = 100) for at least 3 weeks prior to investigation. Time in therapeutic range was 67 % for VKA. Mean CHADS2 score and CHA2DS2-VASc score were 1.3 and 2.5, respectively. Left atrial abnormality was defined as either dense SEC, low LAAV <20 cm/s, or thrombus. RESULTS: Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA. CONCLUSION: With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

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.

Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa has been used in folkloric medicine for the control of blood pressure. We previously found that an extract of Tinospora crispa and its constituents effect the heart rate and blood pressure in anesthetized rats. AIM OF THE STUDY: The aim was to investigate the effects and mechanisms of the Tinospora crispa extract and bioactive components on the rat isolated left atria. MATERIALS AND METHODS: Air-dried stems of Tinospora crispa were extracted with water, followed by partitioning with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble material was concentrated and dried under reduced pressure and lyophilized to obtain a crude powder (Tinospora crispa extract). The active components of Tinospora crispa extract were separated by column chromatography and preparative HPLC. The effects and mechanisms of the n-butanol extract and the bioactive purified components (adenine, uridine, adenosine, salsolinol, tyramine, higenamine, syringin, (-)-litcubinine, borapetoside A, borapetoside B, borapetoside D and borapetoside E) were studied in isolated left atria from normal and reserpinized rats. RESULTS: Tinospora crispa extract caused an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI-118,551 and atenolol but not by phentolamine. Reserpine did not significantly shift the concentration-response curve (C-R curve) of the inotropic effect of the higenamine. ICI-118,551 and atenolol caused a parallel shift of the C-R curve to the right of about 8 and 33 fold, respectively. At low concentrations salsolinol caused a slight increase in the force of contraction of the left atrium, but at higher concentrations a decrease was observed. The negative inotropic effect of salsolinol was significantly inhibited by propranolol and atropine. In the reserpinized isolated left atrium, the negative inotropic effect of salsolinol was potentiated and again this effect was significantly inhibited by propranolol and atropine. Tyramine caused a positive inotropic effect, and this effect was inhibited by propranolol or by pretreatment of the rat with reserpine. Adenosine caused a negative inotropic effect, while uridine caused a slight positive inotropic effect on the left atrium. This effect was significantly inhibited by DPCPX. CONCLUSIONS: Crude extract of Tinospora crispa exert a positive inotropic effect on the electrical field stimulated isolated left atria that results from the concerted action of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating the release of acetylcholine. Adenosine and uridine acted via the purinergic pathways to cause negative inotropic effects on the isolated left atria.

[Influence of new III class antiarrhythmic drug Niferidil (RG-2) on bioelectrical activity of rat pulmonary veins myocardium].

Myocardial cells in pulmonary veins are thought to play a major role in the initiation and maintenance of atrial arrhythmias, including atrial fibrillation. In experiments on rat pulmonary veins, antiarrhythmic drug niferidil (RG-2) produced increase of APD90% and functional refractory period and decrease of action potential amplitude and slope of APD restitution curve. Thus niferidil (RG-2) exerts stronger action on pulmonary veins than left atrium. This can take important part in Niferidil (RG-2) antiarrhythmic activity.

Paradoxical change in atrial fibrillation dominant frequencies with baroreflex-mediated parasympathetic stimulation with phenylephrine infusion.

INTRODUCTION: Parasympathetic stimulation is known to promote atrial fibrillation (AF) through shortening of atrial refractory periods. We hypothesized that baroreflex-mediated parasympathetic stimulation via phenylephrine (PE) infusion would increase AF rate as measured by dominant frequency (DF). METHODS AND RESULTS: The protocol was performed in 27 patients (24 M, 59 ± 1 years old) prior to AF ablation. For 10 patients in AF, PE was infused until systolic blood pressure increased ≥30 mmHg. Electrograms were recorded in the left atrium before and after PE. DFs of each recording were calculated offline. Atrial effective refractory periods (ERPs) were measured before and after PE in 11 patients who were in sinus rhythm during the procedure. DFs were also measured in 6 patients in AF before and after complete parasympathetic blockade with atropine (0.04 mg/kg). PE resulted in increased RR intervals during sinus rhythm (1,170 ± 77 to 1,282 ± 85 ms, P = 0.03) and AF (743 ± 32 to 826 ± 30 ms, P = 0.03), consistent with parasympathetic effect on the sinus and AV nodes, respectively. DFs were decreased by PE in the left atrium (6.2 ± 0.2 to 6.0 ± 0.2 Hz, P = 0.004). Correspondingly, atrial ERPs significantly increased from 218 ± 13 to 232 ± 11 ms (P = 0.04). Atropine resulted in a decreasing trend in DF in the left atrium (5.9 ± 0.1 to 5.8 ± 0.1 Hz, P = 0.07). CONCLUSIONS: Despite baroreflex-mediated parasympathetic effect, PE produced a slowing of AF along with lengthening of ERP, while parasympathetic blockade also slowed DF. It is therefore likely that the direct and indirect adrenergic effects of PE on atrial electrophysiology are more prominent than its parasympathetic effects.

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human pulmonary vein and left atrial electrophysiology in paroxysmal atrial fibrillation.

Omega-3 polyunsaturated fatty acids in fish oils may have antifibrillatory effects; however, their electrophysiologic effects in paroxysmal atrial fibrillation (PAF) remain unknown. The aim of this study was to investigate the effects of chronic fish oil supplementation on human pulmonary vein (PV) and left atrial electrophysiology in PAF. Patients with PAF undergoing PV isolation were randomized ≥1 month before their procedure into a control group (n = 18) or a fish oil group (n = 18) in an unblinded fashion. The latter were supplemented with fish oil 6 g/day for a mean of 40 ± 12 days. Pulmonary venous and left atrial effective refractory periods (ERPs), PV conduction, and susceptibility to AF initiated within PVs were assessed. Compared to the control group, the fish oil group had (1) longer left-sided (p = 0.002) and right-sided (p = 0.001) pulmonary venous ERPs; (2) less dispersion of pulmonary venous ERPs (left PVs p = 0.001, right PVs p = 0.07); (3) longer left atrial ERPs (p = 0.02); (4) no difference in pulmonary venous conduction; (5) lower incidence of AF initiated from PVs during ERP testing (77% vs 31%, p = 0.02); and (6) prolongation of mean AF cycle length (p = 0.009) and shortest AF cycle length in PVs (p = 0.04). In conclusion, patients with PAF chronically supplemented with fish oils exhibit distinctive electrophysiologic properties including prolonged pulmonary venous and left atrial ERPs and decreased susceptibility to initiation AF from within PVs. These changes may in part explain the antifibrillatory effect of chronic omega-3 polyunsaturated fatty acid supplementation in patients with PAF.

Anticholinergic effects of artemisinin, an antimalarial drug, in isolated guinea pig heart preparations.

Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin (1 to 300 microM) inhibited I(K.ACh) induced by extracellular application of both carbachol (1 microM) and adenosine (10 microM) and that induced by intracellular loading of GTPgammaS (100 microM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosine-induced, and GTPgammaS-activated IK.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 microM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 microM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of IK.ACh via inhibition of the muscarinic potassium channel and/or associated GTP-binding proteins.

Epinephrine increases mortality after brief asphyxial cardiac arrest in an in vivo rat model.

Epinephrine may be detrimental in cardiac arrest. In this laboratory study we sought to characterize the effect of epinephrine and concomitant calcium channel blockade on postresuscitation myocardial performance after brief asphyxial cardiac arrest. Anesthesized rats were disconnected from mechanical ventilation, resulting in cardiac arrest. Resuscitation was attempted after 1 min with mechanical ventilation, oxygen, chest compressions, and IV medication. In experimental series 1 and 2, animals were allocated to 10 or 30 microg/kg epinephrine or 0.9% saline. In series 3, animals received 30 microg/kg of epinephrine and were randomized to 0.1 mg/kg of verapamil or to 0.9% saline. In series 1 and 3, left ventricular function was assessed using transthoracic echocardiography. In series 2, left atrial pressure was measured. Epinephrine was associated with increased mortality (0/8 [0%] in controls, 4/12 [33.3%] in 10 microg/kg animals, and 16/22 [72.8%] in 30 microg/kg animals; P < 0.05), hypertension (P < 0.001), tachycardia (P = 0.004), early transient left atrial hypertension, and dose-related reduction in left ventricular end diastolic diameter (P < 0.05). Verapamil prevented mortality associated with large-dose epinephrine (0% versus 100%) and attenuated early diastolic dysfunction and postresuscitation hypertension (P = 0.001) without systolic dysfunction. Epinephrine appears to be harmful in the setting of brief cardiac arrest after asphyxia.

Reversal of atrial mechanical stunning after cardioversion of atrial arrhythmias: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy.

BACKGROUND: Atrial mechanical stunning develops on termination of chronic atrial arrhythmias and is implicated in the genesis of thromboembolic complications after cardioversion. The mechanisms responsible for atrial mechanical stunning are unknown. The effects of atrial rate, isoproterenol, and calcium on atrial mechanical function in patients with atrial stunning have not been evaluated, and it is not known if atrial stunning can be reversed. METHODS AND RESULTS: Thirty-five patients with chronic atrial flutter (AFL) undergoing radiofrequency ablation were studied. Fifteen patients in sinus rhythm undergoing ablation for paroxysmal AFL were studied as control for effects of the procedure. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AFL, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol or calcium. With termination of AFL, LAAEV decreased from 59.0+/-3.7 cm/s to 18.8+/-1.4 cm/s (P<0.0001) and LASEC grade increased from 0.9+/-0.1 to 2.2+/-0.2 (P<0.0001). Pacing increased LAAEV to a maximum of 38.4+/-3.2 cm/s (P<0.0001) and reduced LASEC grade to 1.9+/-0.2 (P=0.005). Isoproterenol and calcium reversed atrial mechanical stunning with LAAEV increasing to 89.3+/-12.6 cm/s (P=0.0007) and 50.2+/-10.5 cm/s (P=0.005), respectively, and LASEC grade decreasing to 0.2+/-0.1 (P=0.001) and 1.4+/-0.2 (P=0.01), respectively. The postpacing pause increased LAAEV to 69.3+/-3.7 cm/s (P<0.0001). No change in LAAEV was observed in the paroxysmal AFL group. CONCLUSION: Atrial mechanical stunning can be reversed by pacing at increased rates and through the administration of isoproterenol or calcium. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium as a result of chronic atrial flutter.

Efficacy of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The efficacies of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin, each as monotherapy, were evaluated in a rabbit model of induced left-sided Pseudomonas aeruginosa endocarditis. Therapy started 48 h after infection and lasted 5 days. All agents were given intramuscularly; amikacin at 7 mg/kg/12 h, and each quinolone at 35 mg/kg/12 h. All animals survived except for 1 of the group that received amikacin, and 2 of the untreated control group. No sterile vegetations were found in the untreated group and the group of fleroxacin, while 3 animals from the amikacin, ofloxacin, and enoxacin groups, and 2 from the ciprofloxacin and pefloxacin groups had sterile vegetations. All agents used significantly reduced the number of CFU per gram of vegetation versus untreated controls. Enoxacin and ciprofloxacin were equipotent and more effective than pefloxacin, ofloxacin and amikacin. Fleroxacin had a weaker activity.

In vitro screening of antitumour agents for cardiotoxicity by means of isolated mouse left atria.

Cardiotoxicity, a side-effect that can occur after treatment with an anticancer drug, has severe clinical implications. Therefore, a model is desired to screen new anticancer drugs or drug combinations for possible cardiotoxic side-effects. In the present study we tested the applicability of the electrically stimulated isolated mouse left atrium model using a wide range of anticancer drugs with known cardiotoxicity. It appeared that the cardiotoxicity observed in our model, i.e. the negative or positive inotropic effects of the drugs on the isolated atrium, corresponded with the observed cardiotoxicity in animals and/or humans. It is therefore concluded that our model can be used to wam for possible cardiotoxic side-effects of anticancer drugs in vivo.

[Effects of isorhynchophylline on physiological characteristics of isolated guinea pig atrium].

Isorhynchophylline (Iso) inhibits the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner, 30 mumol/L markedly depresses adrenaline-induced automaticity, 10 mumol/L prolongs functional refractory period and decreases excitability. Furthermore, 10 mumol/L of Iso reduces the effect of ouabain on contractile force in left atrium and 0.3 mmol/L markedly inhibits the response to paired stimulation.