aconitine and Myocardial-Infarction

Topics: Acetylcholine; Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Glycosides; Chloroform; Disease Models, Animal; Electric Stimulation; Electrophysiology; Heart; Heart Conduction System; Humans; Mice; Myocardial Contraction; Myocardial Infarction; Perfusion; Rats

In order to assess the value and therapeutic safety of an antiarrhythmic drug, it must be submitted to multiple tests, which reproduce as faithfully as possible the conditions observed in human pathology. The main experimental approaches are presented here: screening and control tests. For each test, the authors emphasize the various experimental factors limiting their interpretation and allowing the extrapolation to men.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Aprindine; Coronary Vessels; Dogs; Drug Evaluation, Preclinical; Guinea Pigs; Heart; Isoproterenol; Ligation; Myocardial Infarction; Ouabain; Rats; Ventricular Fibrillation

Allapinin after i.v. bolus infusion in a dose of 30 mg is relatively quickly eliminated from blood (in patients without congestive heart failure half-elimination period is 2.4 +/- 0.5 h and clearance is 79.0 +/- 8.9 l/h) which makes a good reason for its intravenous infusion according to the scheme "load dose + drop infusion". Marked heart failure in patients with acute myocardial infarction compared to patients without heart failure results in reduced elimination rate, decreased clearance, significantly increased plasma allapinin concentration which should be taken in account when choosing the regime of drug infusion. The elimination of allapinin is mainly metabolic and not renal (only about 17% of the drug is excreted with urine).

Topics: Aconitine; Aconitum; Adult; Aged; Clinical Trials as Topic; Female; Half-Life; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Ventricular Fibrillation

Pharmacological modulation of parasympathetic activity with donepezil, an acetylcholinesterase inhibitor, improves the long-term survival of rats with chronic heart failure (CHF) after myocardial infarction (MI). However, its mechanism is not well understood. The α7-nicotinic acetylcholine receptor (α7-nAChR) reportedly plays an important role in the cholinergic anti-inflammatory pathway. The purpose of this study was to examine whether blockade of α7-nAChR, either centrally or peripherally, affects cardioprotection by donepezil during CHF.. One-week post-MI, the surviving rats were implanted with an electrocardiogram or blood pressure transmitter to monitor hemodynamics continuously. Seven days after implantation, the MI rats (n = 74) were administered donepezil in drinking water or were untreated (UT). Donepezil-treated MI rats were randomly assigned to the following four groups: peripheral infusion of saline (SPDT) or an α7-nAChR antagonist methyllycaconitine (α7PDT), and brain infusion of saline (SBDT) or the α7-nAChR antagonist (α7BDT).. After the 4-week treatment, the role of α7-nAChR was evaluated using hemodynamic parameters, neurohumoral states, and histological and morphological assessment. Between the peripheral infusion groups, α7PDT (vs. SPDT) showed significantly increased heart weight and cardiac fibrosis, deteriorated hemodynamics, increased plasma neurohumoral and cytokine levels, and significantly decreased microvessel density (as assessed by anti-von Willebrand factor-positive cells). In contrast, between the brain infusion groups, α7BDT (vs. SBDT) showed no changes in either cardiac remodeling or hemodynamics.. Peripheral blockade of α7-nAChR significantly attenuated the cardioprotective effects of donepezil in CHF rats, whereas central blockade did not. This suggests that peripheral activation of α7-nAChR plays an important role in cholinergic pharmacotherapy for CHF.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Blood Pressure; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Electrocardiography; Heart Failure; Hemodynamics; Male; Myocardial Infarction; Nicotinic Antagonists; Random Allocation; Rats; Rats, Sprague-Dawley

Monoester-diterpenoid alkaloids are the main bioactive components of Sini decoction, which is a well-known traditional Chinese medicine formula for the treatment of myocardial infarction (MI) and heart failure in China. In this work, an ultra-high-performance liquid chromatography-mass spectrometry combined with microdialysis method was successfully established and applied for investigating for the first time comparative plasma pharmacokinetics of three monoester-diterpenoid alkaloids (benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine) in normal and MI rats after oral administration of Sini decoction. The statistical results of pharmacokinetic parameters demonstrated that benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine showed lower peak concentration, longer half-life, smaller area under the concentration-time curve, slower clearance, time to peak concentration and mean residence time in MI rats than in normal rats (p < 0.05), which indicated that monoester-diterpenoid alkaloids exhibited lower systemic exposure and slower elimination in the MI rats. The results provided the experimental basis for understanding the metabolic fate and therapeutic effects of Sini decoction.

Topics: Aconitine; Administration, Oral; Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Drugs, Chinese Herbal; Limit of Detection; Linear Models; Male; Microdialysis; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry

Vagal nerve stimulation (VNS) protects from myocardial and vascular injury following myocardial ischaemia and reperfusion (IR) via a mechanism involving activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR) and reduced inflammation. Arginase is involved in development of myocardial IR injury driven by inflammatory mediators. The aim of the study was to clarify whether VNS downregulates myocardial and vascular arginase via a mechanism involving activation of α7 nAChR following myocardial IR.. Anaesthetized rats were randomized to (i) sham-operated, (ii) control IR (30-min ischaemia and 2-h reperfusion, (iii) VNS throughout IR, (iv) the arginase inhibitor nor-NOHA+IR, (v) nor-NOHA+VNS+IR, (vi) selective α7 nAChR blockade by methyllycaconitine (MLA) followed by VNS throughout IR and (vii) MLA+IR.. Infarct size was reduced by VNS compared to control IR (41 ± 3% vs. 67 ± 2% of the myocardium at risk, P < 0.001). Myocardial IR increased myocardial and aortic arginase activity 1.7- and 3.1-fold respectively (P < 0.05). VNS attenuated the increase in arginase activity compared to control IR both in the myocardium and aorta (P < 0.05). MLA partially abolished the cardioprotective effect of VNS and completely abrogated the effect of VNS on arginase activity. Arginase inhibition combined with VNS did not further reduce infarct size.. Vagal nerve stimulation reduced infarct size and reversed the upregulation of arginase induced by IR both in the myocardium and aorta via a mechanism depending on α7 nAChR activation. The data suggest that the cardioprotective effect of VNS is mediated via reduction in arginase activity.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Arginase; Arginine; Down-Regulation; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Nicotinic Antagonists; Random Allocation; Rats; Rats, Sprague-Dawley; Vagus Nerve Stimulation

A comparative study of the acute toxicity and antiarrhythmic activity of new domestic derivatives of dimethylacetamide showed that the introduction of amino and carboxylic acid residues into the structure of compounds is accompanied by reduction of the toxic properties of new substances on the average 2.73 times (p = 0.002) upon intraperitoneal introduction to animals. It has been established that the derivatives are able to prevent the formation of aconitine induced arrhythmias and eliminate the arrhythmia that occurs on the second day of myocardial infarction in dogs. Original derivatives of dimethylacetamide exhibit antiarrhythmic properties and their activity increases in proportion to the acute toxicity (r = 0.83, p = 0.0043).

Topics: Acetamides; Aconitine; Adjuvants, Immunologic; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cryoprotective Agents; Dogs; Dose-Response Relationship, Drug; Female; Male; Mice; Myocardial Infarction; Rats

Cardiotoxicity in acute aconitine intoxication is well known; however, elevation of troponin I level and abnormal scintigraphy findings had not previously been reported.. A 60-year-old man developed chest tightness, syncope and convulsion after ingesting processed Aconitum carmichaeli (Chuanwu) extract for treatment of headache. Electrocardiogram showed first degree atrioventricular (AV) block. Troponin I level was elevated at 14.8 ng/mL 13 hours post-ingestion. Creatine kinase was also increased to 414 U/L. However, echocardiography did not show any abnormal cardiac wall motion. Tc-99m-PYP scintigraphy revealed diffusely increased uptake in the myocardium, suggesting the presence of myocardial necrosis or myocarditis.. Aconitine poisoning can mimic acute myocardial infarction with chest tightness and elevated cardiac enzymes. Increased cardiac markers and myocardial insult seen in this patient were likely to be related to the toxicity of aconitine. Care should be taken in making the diagnosis in such instances. Management is primarily supportive.

Topics: Aconitine; Creatine Kinase; Diagnosis, Differential; Drugs, Chinese Herbal; Echocardiography; Humans; Male; Middle Aged; Myocardial Infarction; Plant Extracts; Poisoning; Powders; Technetium Tc 99m Pyrophosphate; Troponin I

Intravenous glialin in a dose of 7 mg/kg suppressed the number of ectopic contractions caused by double ligature of the left coronary artery by the method of Harris and almost 2-fold prolonged animal life-span in comparison with the control. The maximum antiarrhythmic effect of glialin developed after 180 min and persisted for 5 h. Glialin injected intravenously (10 mg/kg) after myocardial infarction under conditions of programmed electrical stimulation inhibited conduction of evoked impulse in the atria, Purkinje fibers, and ventricular myocardium and did not modify the effective refractory periods of the atria and ventricles.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dogs; Electrophysiology; Glycyrrhizic Acid; Heart Conduction System; Myocardial Infarction

The present study was designed to test a hypothesis that nonfatal ventricular arrhythmia such as ventricular premature beats (VPB) is a contributing factor in the elevation of blood pressure variability (BPV).. Blood pressure (BP) and electrocardiogram were continuously recorded. The relation between VPB and BPV was observed under conscious state in chronic myocardial infarction (MI) rats one month after ligation of the left coronary artery, and further verified under anesthetized state in rat model of ventricular arrhythmia produced by acute intravenous infusion of aconitine.. MI rats exhibited a big difference in the count and pattern of VPB, and were divided into no VPB, occasional VPB, and frequent VPB groups. Among the three groups, there were no differences in BP, heart period (HP), and MI size. However, BPV was markedly higher in frequent not occasional VPB rats, and HP variability (HPV) was larger in both frequent and occasional VPB rats, when compared with no VPB rats. In the whole population of MI rats, BPV was positively correlated with VPB and HPV, not with BP, HP and MI size. Infusion of aconitine had no effect on BP, HP, BPV, and HPV during the period without VPB. Frequent VPB after several minutes of aconitine infusion induced significant increase in BPV and HPV with no change in BP and HP. BPV was also positively correlated with VPB and HPV, not with BP and HP. Hemodynamics in aconitine-evoked ventricular tachycardia was characterized as lower BP, higher BPV, and higher HPV.. High BPV can be caused by frequent not occasional VPB in rats.

Topics: Aconitine; Animals; Blood Pressure; Heart Rate; Hypertension; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Ventricular Premature Complexes

We have found that intravenous administration of cannabinoid receptor (CB) agonist HU-210 (0.05 mg/kg), increases cardiac resistance against arrhythmogenic effect of epinephrine, aconitine, coronary artery occlusion and reperfusion in rats. Pretreatment with CB2-receptor antagonist, SR144528 (1 mg/kg), completely abolished the antiarrhythmic effect of HU-210. However this effect of HU-210 was not attenuated by pretreatment with CB1-receptor antagonist, SR141716A (3 mg/kg). We also found that HU-210 (0.05 mg/kg) decreased the relationship between infarction size and area of ischemia. It is concluded that CB2 receptor stimulation promotes an increase in the cardiac resistance against arrhythmogenic influences and probably increases myocardial tolerance of both ischemic and reperfusion damages in rats.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Arterial Occlusive Diseases; Camphanes; Cannabinoids; Coronary Artery Disease; Dronabinol; Epinephrine; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

The effects of 6,7,8, 9-tetrahydro-2-methyl-5H-cyclohepta[b]pyridine-3-carbonylguanidine maleate (TY-12533) on myocardial ischemia/reperfusion injury were evaluated in rats. Inhibitory effects of TY-12533, TY-50893 (the 9-chloro derivative of TY-12533) and cariporide on the platelet Na(+)/H(+) exchanger in vitro were almost equal at pH 6.2 and decreased at pH 6.7; but TY-12533 was four times more potent than TY-50893 and cariporide at pH 6.7. TY-12533, TY-50893 and cariporide administered before ischemia (0.01-1 mg/kg, i.v.) suppressed the ischemia/reperfusion-induced arrhythmias to the same extent in vivo; but TY-12533 was more effective than cariporide and TY-50893 when they were administered during ischemia (0.1-1 mg/kg). Similar results were obtained for the inhibitory effects of these drugs administered before ischemia (0.03-0.1 mg/kg, i.v.) and during ischemia (0.1-1 mg/kg) on the ischemia/reperfusion-induced myocardial infarction. These differences between TY-12533 and the other drugs in vitro and in vivo may be ascribed to the pK(a) values of the guanidinium moiety of TY-12533 (6.93), TY-50893 (6.35) and cariporide (6.28).

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Disease Models, Animal; Guanidines; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Pyridines; Rats; Rats, Wistar; Sodium-Hydrogen Exchangers; Sulfones

Single intravenous allapinine, 30 mg, given to patients with acute myocardial infarction, including those with moderate circulatory insufficiency, fails to affect central hemodynamic parameters or has a favourable action: normalizes pulmonary diastolic pressure, cardiac index, diminishes total peripheral vascular resistance. The agent also produces a weak antihypertensive effect and increases heart rate.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction

Hibernators are resistant to ventricular fibrillation (VF) induced by hypothermia. This is in contrast to non-hibernating mammals which develop circulatory arrest, usually VF, in the temperature region 15-20 degrees C. The hedgehog which is a hibernator showed resistance to VF also when VF-evoking procedures other than hypothermia were used, such as local application of aconitine on the epicardium, administration of 0.55 M CaCl2 to isolated hearts perfused with a potassium-free modified Tyrode solution, injection of procaine HCl into isolated hearts perfused with a modified Tyrode solution after previous adrenaline administration, and ligation of the left descending coronary artery. Electrical stimulation in the vulnerable period produced VF in some but not in all the hedgehogs but a greater current was necessary than in guinea-pigs, all of which developed VF. Factors of possible importance to explain this difference in VF resistance are the QT duration which is short in hibernators, adrenergic innervation (ventricular muscle fibres in hibernators lack sympathetic innervation), metabolic factors (different temperature activity curves in hibernators compared to nonhibernating mammals) and ultrastructure (less skeletin filament in the conduction system of the hedgehog heart).

Topics: Aconitine; Adrenergic Fibers; Animals; Body Temperature Regulation; Bundle-Branch Block; Calcium Chloride; Cardiac Pacing, Artificial; Electrocardiography; Energy Metabolism; Female; Guinea Pigs; Heart Rate; Hedgehogs; Hibernation; Humans; Hypocalcemia; Long QT Syndrome; Middle Aged; Myocardial Infarction; Procaine; Ventricular Fibrillation