This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.
Alkaloids ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrestins ; metabolism ; Colitis, Ulcerative ; metabolism ; pathology ; prevention & control ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Quinolizines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, delta ; metabolism ; Signal Transduction ; drug effects ; beta-Arrestins

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; etiology ; physiopathology ; prevention & control ; Benzylamines ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; metabolism ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Endocardium ; drug effects ; physiopathology ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Long QT Syndrome ; complications ; Pericardium ; drug effects ; physiopathology ; Piperidines ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Pyridines ; pharmacology ; Rabbits ; Sulfonamides ; pharmacology ; Torsades de Pointes ; etiology ; physiopathology ; prevention & control

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Animals ; Anti-Arrhythmia Agents ; administration & dosage ; Antibiotics, Antineoplastic ; Carbazoles ; administration & dosage ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; Heart Rate ; drug effects ; Male ; Metoprolol ; administration & dosage ; Oxidative Stress ; drug effects ; Propanolamines ; administration & dosage ; Rabbits ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced ; physiopathology ; prevention & control

PURPOSE: Hybrid therapy with catheter ablation of the cavo-tricuspid isthmus (CTI) and continuation of anti-arrhythmic drugs (AAD), or electrical cardioversion with AADs might be alternative treatments for patients with persistent atrial fibrillation (AF). The goal of study was to assess the long term success rate of hybrid therapy for persistent AF compared to antiarrhythmic medication therapy after electrical cardioversion and identify the independent risk factors associated with recurrence after hybrid therapy. MATERIALS AND METHODS: A total of 32 patients with persistent AF who developed atrial flutter after the administration of a class Ic or III anti-arrhythmic drug were enrolled. This group was compared with a group (33 patients) who underwent cardioversion and received direct current cardioversion with AADs. Baseline data were collected, and electrocardiogram and symptom driven Holter monitoring were performed every 2-4 months. RESULTS: There was no significant difference in the baseline characteristics between the groups. The 12 month atrial arrhythmia free survival was better in the hybrid group, 49.0% vs. 33.1%, p=0.048. However, during a mean 55.7+/-43.0 months of follow up, the improved survival rate regressed (p=0.25). A larger left atrium size was an independent risk factor for the recurrence of AF after adjusting for confounding factors. CONCLUSION: Despite favorable outcome during 12 month, the CTI block with AADs showed outcomes similar to AAD therapy after electrical cardioversion over a 12 month follow up period. Minimal substrate modification with AADs might be an alternative treatment for persistent AF with minimal atrial remodeling.
Adult ; Aged ; Anti-Arrhythmia Agents/*therapeutic use ; Atrial Fibrillation/*drug therapy/mortality/*surgery ; Catheter Ablation/*methods/mortality ; Combined Modality Therapy ; *Electric Countershock/mortality ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications/mortality/prevention & control ; Retrospective Studies ; Risk Factors ; *Tricuspid Valve

BACKGROUNDAtrial fibrillation (AF) is one of the most common arrhythmia after coronary artery bypass grafting (CABG), which not only increases the suffering of the patients, but also prolongs hospital stay and enhances cost of care, especially for patients older than 70 years. This study was designed to evaluate the efficacy and safety of low-dose amiodarone in the prevention of AF after CABG, especially for the elderly.

METHODSTwo hundred and ten senile patients undergoing off-pump CABG were included in this prospective, randomized, double-blind and placebo controlled study. Patients were given 10 mg/kg of amiodarone (low-dose amiodarone group, n = 100) or placebo (control group, n = 110) daily for 7 days before surgery and followed by 200 mg of amiodarone or placebo daily for 10 days postoperatively.

RESULTSPostoperative AF occurred in 16 patients (16%) receiving amiodarone and in 36 (37.7%) patients receiving placebo (P = 0.006). AF occurred at (58.13 +/- 16.63) hours after CABG in the low-dose amiodarone group and at (45.03 +/- 17.40) hours in the control group (P = 0.018). The maximum ventricular rate during AF was significantly slower in the low-dose amiodarone group ((121.42 +/- 28.91) beats/min) than in the control group ((134.11 +/- 30.57) beats/min, P = 0.036). The duration of AF was (10.92 +/- 9.56) hours for the low-dose amiodarone group compared with (14.81 +/- 10.37) hours for the control group (P = 0.002). The postoperative left ventricular ejection fraction (LVEF) was significantly improved in the low-dose amiodarone group (from (59.9 +/- 10.3)% to (63.4 +/- 11.4)%, P = 0.001), and significantly higher compared with the control group ((58.5 +/- 10.7)%, P = 0.002). Both groups had a similar incidence of complication other than rhythm disturbances (12.0% vs 16.4%, P = 0.368). The low-dose amiodarone group patients had shorter hospital stays ((11.8 +/- 3.2) days vs (13.8 +/- 4.7) days, P = 0.001) and lower cost of care (RMB (79 115 +/- 16 673) Yuan vs RMB (84 997 +/- 21 587) Yuan, P = 0.031) than that of control group patients. The in-hospital mortality was not significantly different between the two groups (1.0% vs 0.9%, P = 0.946).

CONCLUSIONSPerioperative low-dose oral amiodarone appeared to be cost-effective in the prevention and delay of new-onset postoperative AF in aged patients. It significantly reduced ventricular rate and duration of AF after CABG, decreased hospital cost and stay, as well as promoted the amelioration of left ventricular systolic function. Furthermore, low-dose amiodarone was safe to use and well tolerated with low toxic and side effects, and did not increase the risk of complications and mortality. It is proved to be a first-line therapy and as routine prophylaxis for AF after CABG, especially for elderly patients complicated with left ventricular dysfunction.

Aged ; Amiodarone ; administration & dosage ; Anti-Arrhythmia Agents ; administration & dosage ; Atrial Fibrillation ; etiology ; prevention & control ; Coronary Artery Bypass ; adverse effects ; Double-Blind Method ; Drug Administration Schedule ; Female ; Humans ; Male ; Treatment Outcome

OBJECTIVE: To investigate the effect of fructose-1,6-diphosphete(FDP) on myocardial preservation in pulmonary operations. METHODS: One hundred and six patients undergoing selective pulmonary lobectomy or segmentectomy were randomly divided into 2 groups with 53 patients each. FDP 200 mg/kg was infused intravenously before anesthesia in the FDP group, while 5% glucose with the same volume was given instead of FDP in the control group. ECGs were monitored from before the anesthesia to 72 h after the operation;the time and type of arrhythmia were recorded. Blood samples were taken before the operation (T0), immediately after the operation(T1), at 24 h(T2),48 h(T3)and 72 h(T(4)) after the operation to determine plasma creatine kinase isoenzyme MB(CK-MB) and cardiac troponin I(cTnI) concentrations. RESULTS: The incidence of arrhythmia in FDP group (35 times) was significantly lower than that in the control group(67 times). The incidence of all types of arrhythmia in the FDP group was also significantly lower than that in the control group. The concentrations of CK-MB and cTnI in the FDP group were significantly lower than those in the control group at T1, T2, T3, and T4. CONCLUSION FDP is effective for myocardial preservation in pulmonary operations.
Aged ; Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; etiology ; prevention & control ; Creatine Kinase, MB Form ; blood ; Female ; Fructosediphosphates ; therapeutic use ; Humans ; Male ; Middle Aged ; Pneumonectomy ; adverse effects ; Troponin I ; blood

OBJECTIVEThis study was designed to compare clinical efficacy of segmental pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF).

METHODSPatients with lone PAF were treated with amiodarone alone (A, n = 52), segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12 months follow-up period.

RESULTSDuring follow-up, AF was documented in 24 patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated a significant equally reduction in AF recurrence in SPVI and AL groups (P = 0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A group. The hazard ratio for AF recurrence in patients treated with SPVI and amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46 (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in AL group, P > 0.05).

CONCLUSIONThe results of this study suggest that the segmental pulmonary vein isolation and amiodarone plus losartan are superior to amiodarone alone for preventing AF recurrence in patients with lone PAF.

Aged ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Atrial Fibrillation ; prevention & control ; therapy ; Catheter Ablation ; methods ; Combined Modality Therapy ; Follow-Up Studies ; Humans ; Losartan ; therapeutic use ; Middle Aged ; Prospective Studies ; Treatment Outcome

OBJECTIVETo compare the actions of the three flavone ingredients in choerospondias axillaris on arrhythmias Induced by aconitine.

METHODLangendorff 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.

RESULTCompared 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.

CONCLUSIONSample 1 and sample 2 both resisted the occurrence of arrhythmias induced by aconitine, sample 3 markedly promoted the occurrence of arrhythmias induced by aconitine.

Aconitine ; Anacardiaceae ; chemistry ; Animals ; Anti-Arrhythmia Agents ; isolation & purification ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; prevention & control ; Dose-Response Relationship, Drug ; Female ; Flavones ; isolation & purification ; therapeutic use ; In Vitro Techniques ; Male ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

AIMTo clarify mechanisms that the antiarrhythmic effects of matrine and berbamine are weaker than those of amiodarone and RP58866.

METHODSExperimental arrhythmic models were induced by aconitine, coronary artery ligation and electric stimulation in rats and rabbits. Whole-cell patch-clamp techniques were used to record IK1, IKr, IKs and Ito.

RESULTSMatrine and berbamine significantly increased the dose of aconitine for induction of ventricular premature and ventricular tachycardia in rats, decreased the number of arrhythmias induced by coronary artery ligation in rats and increased ventricular fibrillation threshold (VFT) induced by electric stimulation in rabbits, but the anti-arrhythmic potency of matrine and berbamine was lower than that of amiodarone and RP58866. The inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866. The IC50 of matrine for IK1, IKr, IKs, Ito were (46 +/- 3), (32.9 +/- 1.2), (37 +/- 8) and (7.6 +/- 0.5) mol x L(-1), respectively. The IC50 of amiodarone for IK1, IKr, IKs, Ito were (21 +/- 5) , (3.7 +/- 0.7), (5.9 +/- 0.9) and (5.9 +/- 0.6) mol x L(-1), respectively.

CONCLUSIONThe inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866, which might be the reason that the antiarrhythmic effects of matrine and berbamine were weaker than those of amiodarone and RP58866.

Aconitine ; Alkaloids ; pharmacology ; Amiodarone ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; prevention & control ; Benzylisoquinolines ; pharmacology ; Chromans ; pharmacology ; Dogs ; Female ; Guinea Pigs ; Male ; Piperidines ; pharmacology ; Potassium Channels ; drug effects ; Quinolizines ; Rabbits ; Rats

AIMTo study the effect of modified starfish sterol [C03, succinic acid (5-epiandroene-17-one-3beta-ol) diester] on experimental arrhythmias.

METHODSArrhythmias were induced by drugs (Aco, Oua, BaCl2 and adrenalin) i.v., ligating the left anterior descending coronary artery and electricity.

RESULTSC03 71.4 mg x kg(-1) (ig) was shown to increase the dose of Oua inducing VP, VT, VF and CA in guinea pigs (P < 0.01); C03 (26.8, 80.4 mg x kg(-1)) was found to increase the dose of Aco inducing VF and CA in rats (P < 0.01); C03 (8.9, 26.8, 80.4 mg x kg(-1)) increase the dose of barium chloride and delay the onset time of ventricular arrhythmias (P < 0.01); C03 (14.1, 42.3 mg x kg(-10) shorten time of recovering induced by adrenalin in rabbits (P < 0.01); C03 (80.4 mg x kg(-1)) was shown to reduce the number of ventricular arrhythmias induced by coronary artery ligation in rats (P < 0.05), C03 increase VFT induced by electricity in rabbits, VFT of C03 14.1 mg x kg(-1) increased from (5.1 +/- 2.5) V to (11.0 +/- 2.7) V (P < 0.01), 42.3 mg x kg(-1) increased from (6.1 +/- 1.7) V to (15 +/- 5) V (P < 0.01).

CONCLUSIONStarfish sterol has anti-arrhythmic effect.

Aconitine ; Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; prevention & control ; Barium Compounds ; Cats ; Chlorides ; Epinephrine ; Guinea Pigs ; Materia Medica ; isolation & purification ; therapeutic use ; Mice ; Ouabain ; Rabbits ; Rats ; Starfish ; chemistry ; Sterols ; isolation & purification ; therapeutic use ; Ventricular Fibrillation ; physiopathology