lignans and Arrhythmias--Cardiac

Arctigenin (ATG) has been shown to possess anti-inflammatory, immunemodulatory, anti-viral, anti-microbial, anti-carcinogenic, vasodilatory and anti-platelet aggregation properties. However, the protective role of ATG in prevention of arrhythmias induced by myocardial ischemia/reperfusion is unknown. The aim of this study was to investigate the anti-arrhythmia effect of ATG in an ischemia/reperfusion injured rat heart model and explore the related mechanisms.. Rats were randomly exposed to sham operation, myocardial ischemia/ reperfusion (MI/R) alone, ATG+ MI/R, pretreated with ATG in low (12.5 mg/kg/day), medium (50 mg/kg/day) and high dose (200 mg/kg/day), respectively. Ventricular arrhythmias were assessed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in myocardial tissue were determined by chemical analysis.. Compared to MI/R, rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/day showed significantly reduced incidence and duration of ventricular fibrillation, ventricular tachycardia and ventricular ectopic beat (VEB), and decreased the arrhythmia score during the 30-min ischemia. Incidence and duration of ventricular tachycardia, infarction size and arrhythmia scores in these groups were significantly decreased during the 120-min reperfusion. No ventricular fibrillation occurred during the period of reperfusion. Rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/ day markedly enhanced the activities of antioxidant enzymes SOD and GSH-Px, reduced the level of MDA. No differences were observed between the group pretreated with a low dose of ATG and the sham group. Administration of ATG significantly increased the expression of antioxidant stress protein Nrf2, Trx1 and Nox1.. Our data suggested that ATG plays anti-arrhythmia role in ischemia/reperfusion injury, which is probably associated with attenuating oxidative stress by Nrf2 signaling pathway.

Topics: Animals; Arrhythmias, Cardiac; Disease Models, Animal; Furans; Glutathione Peroxidase; Lignans; Male; Malondialdehyde; Myocardial Infarction; Myocardium; NADPH Oxidase 1; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Thioredoxins

Our previous studies suggested that deoxyschizandrin (DSD) and schisantherin A (STA) may have cardioprotective effects, but information in this regard is lacking. Therefore, we explored the protective role of DSD and STA in myocardial ischemia-reperfusion (I/R) injury.. Anesthetized male rats were treated once with DSD and STA (each 40 µmol/kg) through the tail vein after 45 min of ischemia, followed by 2-h reperfusion. Cardiac function, infarct size, biochemical markers, histopathology and apoptosis were measured and mRNA expression of gp91 (phox) in myocardial tissue assessed by RT-PCR. Neonatal rat cardiomyocytes were pretreated with DSD and STA and then damaged by H2O2. Cell apoptosis was tested by a flow cytometric assay. Compared with the I/R group: (i) DSD and STA could significantly reduce the abnormalities of LVSP, LVEDP, ±dp/dtmax and arrhythmias, thereby showing their protective roles in cardiac function; (ii) DSD and STA could significantly attenuate the infarct size and MDA release while increasing SOD activity, suggesting a role in reducing myocardial injury; (iii) tissue morphology and myocardial textual analysis revealed that DSD and STA mitigated changes in myocardial histopathology; (iv) DSD and STA decreased apoptosis (33.56±2.58% to 10.28±2.80% and 10.98±1.99%, respectively) and caspase-3 activity in the myocardium (0.62±0.02 OD/mg to 0.38±0.02 OD/mg and 0.32±0.02 OD/mg, respectively), showing their protective effects upon cardiomyocytes; and (v) DSD and STA had similar protective effects on I/R injury as those seen with the positive control metoprolol. In vitro, DSD and STA could significantly decrease the apoptosis of neonatal cardiomyocytes.. These data suggest that DSD and STA can protect against myocardial I/R injury. The underlining mechanism may be related to their role in inhibiting cardiomyocyte apoptosis.

Topics: Animals; Apoptosis; Arrhythmias, Cardiac; Cardiotonic Agents; Caspase 3; Cyclooctanes; Cytoprotection; Dioxoles; Disease Models, Animal; Gene Expression Regulation; Hemodynamics; Hydrogen Peroxide; Lignans; Male; Malondialdehyde; Membrane Glycoproteins; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; NADPH Oxidase 2; NADPH Oxidases; Polycyclic Compounds; Rats; Rats, Wistar; RNA, Messenger; Superoxide Dismutase

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms.. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by.. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine.. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect.

Topics: Aconitine; Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channels, L-Type; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Furans; Ion Channels; Lignans; Male; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium Channels; Rats; Rats, Wistar; Sodium Channels

The accumulation of oxygen-free radicals and activation of neutrophils are strongly implicated as important pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. It has been proven that various antioxidants have cardioprotective effects. Magnolol, an active component extracted from the Chinese medicinal herb Magnolia officinalis, possesses potent antioxidant and free radical scavenging activities. In this study, the cardioprotective activity of magnolol was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. The results demonstrated that pretreatment with magnolol (0.2 and 0.5 microg/kg, i.v. bolus) at 10 min before 45 min of left coronary artery occlusion, significantly suppressed the incidence of ventricular fibrillation and mortality when compared with the control group. Magnolol (0.2 and 0.5 microg/kg) also significantly reduced the total duration of ventricular tachycardia and ventricular fibrillation. After 1 h of reperfusion, pretreatment with magnolol (0.2 and 0.5 microg/kg) caused a significant reduction in infarct size. In addition, magnolol (0.2 microg/kg) significantly reduced superoxide anion production and myeloperoxidase activity, an index of neutrophil infiltration in the ischemic myocardium. In addition, pretreatment with magnolol (0.2 and 0.5 microg/kg) suppressed ventricular arrhythmias elicited by reperfusion following 5 min of ischemia. In vitro studies of magnolol (5, 20 and 50 microM) significantly suppressed N-formylmethionyl-leucyl-phenylalanine (fMLP; 25 nM)-activated human neutrophil migration in a concentration-dependent manner. It is concluded that magnolol suppresses ischemia- and reperfusion-induced ventricular arrhythmias and reduces the size of the infarct resulting from ischemia/reperfusion injury. This pronounced cardioprotective activity of magnolol may be mediated by its antioxidant activity and by its capacity for neutrophil inhibition in myocardial ischemia/reperfusion.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biphenyl Compounds; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Female; Hemodynamics; Lignans; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Neutrophils; Peroxidase; Rats; Rats, Sprague-Dawley; Superoxides

Magnolol, an antioxidant, has been reported to possess various protective effects on the cardiovascular system. However, its effect on myocardial stunning has not been elucidated. The purpose of this study was to investigate the antistunning effect of magnolol by evaluating the recovery of regional myocardial function after 10-minute coronary artery occlusion in anesthetized, open-chest rabbits. There was no significant hemodynamic change after intravenous infusion of magnolol. Systolic wall thickening fraction (WThF) measured with an epicardial Doppler sensor in animals pretreated with normal saline and vehicle solution remained significantly depressed (60 +/- 7% and 77 +/- 4% of baseline WThF, respectively) 3 hours after coronary artery reperfusion (CAR). Pretreatment with magnolol (10(-7) and 10(-6) g/kg, intravenous infusion) significantly enhanced the recovery of systolic wall thickening fraction (98 +/- 1 and 99 +/- 1% of baseline WThF, respectively) 60 minutes after CAR. This study demonstrated that intravenous pretreatment with magnolol protected myocardium against stunning.

Topics: Animals; Anti-Arrhythmia Agents; Antioxidants; Arrhythmias, Cardiac; Biphenyl Compounds; Heart; Infusions, Intravenous; Lignans; Male; Myocardial Stunning; Rabbits

This study was designed to evaluate the in vivo effect of magnolol and honokiol on the acute phase of coronary ligation in the presence of nitric oxide inhibitor (L-NAME) or cyclooxygenase inhibitor (aspirin). After Sprague-Dawley rats were anesthetized with urethane, the changes of ventricular arrhythmia induced by coronary ligation for 30 min were determined with or without pretreatment with study medications. The incidence and duration of ventricular arrhythmia were significantly reduced after intravenous pretreatment (15 min before coronary ligation) with 10(-7) g/kg magnolol or 10(-7) g/kg honokiol. However, the antiarrhythmic effect of magnolol or honokiol could be abolished with the pretreatment of 1 mg/kg L-NAME, but not with pretreatment of 100 mg/kg aspirin. The abolishment of the myocardial beneficial effect of magnolol and honokiol by L-NAME, instead of aspirin, suggests an involvement of an increased nitric oxide synthesis in the protection offered by magnolol and honokiol against arrhythmia during myocardial ischemia.

Topics: Anesthesia; Animals; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Arrhythmias, Cardiac; Aspirin; Biphenyl Compounds; Blood Pressure; Coronary Disease; Enzyme Inhibitors; Lignans; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley

1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more potent than alpha-tocopherol in inhibiting lipid peroxidation in rat heart mitochondria. In the present study, the in vivo antiarrhythmic and anti-ischaemic effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague-Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10(-7), 10(-8) and 10(-9) g/kg, was administered intravenously 15 min before ligation of the coronary artery. 3. The incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the relief of coronary ligation were also reduced. 4. In rats subjected to 4 h coronary ligation, 10(-7) and 10(-8) g/kg magnolol significantly reduced infarct size. 5. We conclude that magnolol may protect the myocardium against ischaemic injury and suppress ventricular arrhythmia during ischaemia and reperfusion.

Topics: Analysis of Variance; Animals; Arrhythmias, Cardiac; Biphenyl Compounds; Ligation; Lignans; Male; Myocardial Ischemia; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley