Aconitine Poisoning Research Articles

Extracorporeal membrane oxygenation combined with hemoperfusion to assist in the rescue of aconitine poisoning: A case report.

Extracorporeal membrane oxygenation (ECMO) has been widely used as a clinical bridge for cardiopulmonary failure. We recently used combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and haemoperfusion to successfully treat a patient with acute aconitine poisoning. The patient was admitted to the Emergency Intensive Care Unit (EICU) in a state of coma and shock. Her received comprehensive treatment, including haemoperfusion and anti-shock therapy. 40 minutes after admission, the patient experienced sudden respiratory and cardiac arrest. After conventional defibrillation and cardiopulmonary resuscitation proved ineffective, veno-arterial ECMO was immediately initiated. One hour after initiation of VA-ECMO, the patient's heart rhythm stabilised to sinus rhythm. After 33 h of supportive care, the patient was awake, haemodynamically stable and the VA-ECMO was successfully removed. The patient made full recovery 7days after admission.

Ventricular arrhythmias and cardiac arrest in aconitine poisoning: a case report

In traditional Chinese medicine, aconitum plants and roots are frequently used after extensive processing to treat various ailments in humans. However, use of a larger than recommended dose and inadequate processing increase the risk of aconitine poisoning. As a result of its particular mechanism of toxicity, aconitine poisoning can present with a variety of arrhythmias, including ventricular ectopy, ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Meticulous arrythmia treatment is needed to restore sinus rhythm. We report a case of ventricular arrhythmias (VAs) induced by accidental aconitine poisoning. Our case highlights the efficacy of amiodarone in treating aconitine-induced VAs. To the best of our knowledge, this is one of the first described cases of aconitine-induced VAs in Europe. Clinicians should be aware of potential rare toxicological causes of malignant arrhythmias and consider toxicological screening in otherwise etiologically unexplained sudden cardiac arrest.

Intentional intoxication with monkshood plant leading to atrioventricular dissociation and ventricular ectopy in a 17-year-old female: a case report

BackgroundMonkshood, a toxic plant containing a potent cardio- and neurotoxin called aconitine, can lead to a range of symptoms, including nausea, vomiting, dizziness, seizures, and cardiac arrhythmias. Mortality associated with this intoxication are due to ventricular tachyarrhythmias which are difficult to treat and often refractory in nature.Case presentationWe present a case of a 17-year-old female patient who presented to the emergency department after intentionally ingesting a monkshood plant and developed atrioventricular dissociation and frequent ventricular ectopy. The patient was successfully treated with activated charcoal, supportive care, and cardiac monitoring.ConclusionThis case highlights the importance of early recognition of aconitine poisoning and the need for prompt supportive care, cardiac rhythm monitoring, and preemptive antiarrhythmic treatment planning.

Recurrent malignant ventricular arrhythmias and paresthesia—a mystery revealed as aconitine poisoning: a case report

BackgroundWe report a case of a clinical challenge lasting for 12 months, with severe and unresolved clinical features involving several medical disciplines.Case presentationA 53-year-old Caucasian male, who had been previously healthy apart from a moderate renal impairment, was hospitalized 12 times during a 1-year period for a recurrent complex of neurological, cardiovascular, and gastrointestinal symptoms and signs, without any apparent etiology. On two occasions, he suffered a cardiac arrest and was successfully resuscitated. Following the first cardiac arrest, a cardiac defibrillator was inserted. During the 12th admission to our hospital, aconitine poisoning was suspected after a comprehensive multidisciplinary evaluation and confirmed by serum and urine analyses. Later, aconitine was also detected in a hair segment, indicating exposure within the symptomatic period. After the diagnosis was made, no further episodes occurred. His cardiac defibrillator was later removed, and he returned to work. A former diagnosis of epilepsy was also abandoned. Criminal intent was suspected, and his wife was sentenced to 11 years in prison for attempted murder. To make standardized assessments of the probability for aconitine poisoning as the cause of the eleven prior admissions, an “aconitine score” was established. The score is based on neurological, cardiovascular, gastrointestinal, and other clinical features reported in the literature. We also make a case for the use of hair analysis to confirm suspected poisoning cases evaluated after the resolution of clinical features.ConclusionThis report illustrates the medical challenge raised by cases of covert poisoning. In patients presenting with symptoms and signs from several organ systems without apparent cause, poisoning should always be suspected. To solve such cases, insight into the effects of specific toxic agents is needed. We present an “aconitine score” that may be useful in cases of suspected aconitine poisoning.

Fatal poisoning due to aconite: Autopsy findings and postmortem quantitative analysis.

Aconitum species are commonly used in traditional Chinese medicine, and they have a narrow therapy window due to the possibility of aconitine poisoning. Aconitine poisoning deaths appear infrequently in forensic practice. It is important to collect valuable body samples in time due to the rapid absorption and excretion of aconitine. However, it is unknown whether postmortem samples have value for toxicological analysis if the deceased has experienced long-term treatment before death. Herein, we present a case of a woman who died after 12 days of failed active treatment for aconitine poisoning. Aconitine was detected in the liver tissue. To our knowledge, this is the first case report describing the detection of aconitine in a decedent after long-term active treatment. The findings indicated that the aconitine concentration in liver tissue can be maintained after long-term treatment; this information may therefore serve as a reference in forensic practice.

Left Stellate Ganglion Blockade for Refractory Ventricular Arrhythmias With Aconitine Poisoning: A Case Report.

Aconitine poisoning causes refractory ventricular arrhythmias (VAs). In a 20-year-old man, VAs of unknown etiology did not respond to drugs and electrical defibrillation. However, left stellate ganglion blockade (SGB) dramatically decreased arrhythmias without complications. At a later date, we found that refractory VAs were caused by aconitine poisoning. Left SGB is effective for treating refractory VAs with aconitine poisoning and can be easily performed with few complications for VAs of unknown etiology even if patients are receiving anticoagulant therapy. Also, left SGB can be performed to diagnose refractory VAs.

Acute Poisoning of Aconitum

Aconitine, a plant alkaloid is a usual constituent of various over-the-counter herbal remedies and is an uncommon cause of deliberate poisoning. Herein, we describe an unusual case of poisoning in a young male due to accidental ingestion of aconitine tincture. On presentation, his electrocardiogram documented ventricular arrhythmias for which amiodarone was administered promptly. This led to considerable improvement in heart rhythm. The patient recovered gradually with this management and achieved normal sinus rhythm. He was completely asymptomatic within 5 days of treatment and subsequently discharged. Our management with amiodarone narrates the importance of this drug in aconitine poisoning, which can prove to be fatal in the absence of any intervention or delay in diagnosis. Nonexistence of specific antidote also establishes amiodarone as a standard remedy.

Clinical effect of a temporary pacemaker on an electrical storm induced by severe acute aconitine poisoning

In China, medicinal liquor made from the aconitine root soaked in wine is poisoned. At present, reliable detoxification drugs are not available. The present study used a temporary pacemaker to treat 12 patients who required treatment due to an electrical storm caused by aconitine poisoning between June, 2017 and April, 2021. The results revealed that temporary pacing was successful in all 12 patients. The electrode placement rate was 100%, and the effective cardiac pacing rate was 100%. The blood pressure of the patients gradually returned to normal levels. Ventricular tachycardia and high‑grade atrioventricular block were terminated. As regards atrial premature beats and ventricular premature beats, the sinus rhythm was restored after continuous amiodarone pumping. Simultaneously, fluid supplementation and control supportive treatment were administered. The patients were hospitalized for 4‑6 days. The patients' symptoms disappeared, their vital signs were stable and their electrocardiogram (ECG) exhibited normal findings. The 12 patients were followed‑up for 1 week following discharge and did not have any discomfort; the ECG revealed no abnormalities. On the whole, the findings of the present study suggest that temporary cardiac pacing may be an effective treatment for malignant arrhythmias caused by severe acute aconitine poisoning. However, the present study only involved a very small number of cases. In the future, further studies are required with larger sample, and further randomized, controlled multi‑center studies are also warranted to these findings.

Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis.

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

Reflections on the aconitine poisoning

Aconitine is a natural toxic substance belonging to the family of aconitum alkaloids, which is used in small doses by Traditional Chinese practitioners. We present a case of accidental death due to acute aconitine poisoning. A 65-year-old Chinese man presented to a medical clinic with fever and shoulder pain. Soon after administration of intravenous ceftriaxone, a bottle of Chinese medicinal wine was administered. The man rapidly experienced headache, hearing loss and tinnitus, nausea, diarrhea, numbness of the lips, tongue, face, and the upper and lower extremities, cold sweat,fall of blood pressure, and discomfort of the entire body, and he died on the same day. Postmortem examination showed cyanosis of the nail beds, severe congestion in lungs and other organs, bilateral pleural effusions, and infiltration of basophils in the intestinal submucosa. No significant increase of IgE was found in the blood. Toxicological analysis detected aconitine in the medicinal wine, blood, and stomach contents by liquid chromatography-tandem mass spectrometry (LC-MS⁄MS). Aconitine was quantified in cardiac blood as 16.4ng/ml, and in stomach contents (63.8ng/ml) and wine sample (10.1 ug/ml). The cause of death was aconitine poisoning. This case report highlights the danger of aconitine. LC-MS⁄MS has the advantages of high analytic speed, sensitivity, and accuracy. It would be desirable for the government to control the use of aconitine-containing herbal extracts.

Potential Molecular Mechanisms and Drugs for Aconitine-Induced Cardiotoxicity in Zebrafish through RNA Sequencing and Bioinformatics Analysis.

BackgroundAccumulating evidence suggests that cardiotoxicity is one of the main manifestations of aconitine (AC) poisoning. However, the molecular mechanism of AC-induced cardiotoxicity remains unclear, there is little direct evidence for therapeutic targets and drugs of AC-induced cardiotoxicity.Material/MethodsZebrafish were exposed to AC to evaluate cardiotoxicity by calculating the heart rates and observing the changes of cardiac and vascular structure. RNA-seq (RNA sequencing) and bioinformatics analysis were used to obtain differentially expressed genes (DEGs). The anti-AC cardiotoxicity compound was identified via connectivity map (CMAP) analysis and molecular docking.ResultsAC-induced cardiotoxicity in zebrafish predominantly included arrhythmias, extended sinus venous and bulbus arteriosus (SV-BA) distance, and larger pericardial edema aera. A total of 1380 DEGs were identified by RNA-seq and bioinformatics analysis. cyclin-dependent kinase-1 (CDK1) was screened as the hub gene and the most potential therapeutic target due to its significant downregulation in cardiotoxicity based on protein-protein interaction (PPI) and drug-gene interaction (DGIdb) network analysis. Cell cycle signal pathway was the most significant pathways identified in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, the expression of CDK1 was validated in the Gene Expression Omnibus (GEO) database GSE71906, GSE65705, and GSE95140. Finally, heptaminol was identified as a novel anti-AC cardiotoxicity compound via CMAP analysis and molecular docking.ConclusionsTotally, hub genes and key pathways identified in this study can aid in the understanding of the molecular changes in AC-induced cardiotoxicity. Meanwhile, we provide a systematic method to explore drug toxicity prevention and treatment.

Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Establishment and verification of risk assessment scale for clinical safety medication of aconitine

Chinese patent medicine containing aconitine is the key in clinical rational drug use. These drugs contain Chuanwu, Caowu or Fuzi, and Aconitum brachypodum with functions of expelling wind-dampness or tonifying Yang, all of which shall be used by strictly following the indications and dosage. However, there are many kinds of such drugs. Not only the unfamiliar knowledge of some Chinese and Western physicians about the characteristics of them, but also the combination of multiple drugs from different clinical departments, would increase the risk of aconitine poisoning. Based on the previous research, this paper proposed three core elements "syndrome differentiation-dosage differentiation-toxicity differentiation" from the prescription review and pharmacy consulting work, and objective and standardized evaluation was used to build a risk assessment scale containing 3 categories, 9 items and 36 indicators with Hulisan Jiaonang and Qufeng Zhitong Jiaonang as the example. This scale was used to evaluate the risk of a therapeutic regimen before and after the implementation. According to the verification of the existing adverse reaction cases, the risk assessment scale can be used to indicate the risk of drug treatment program and identify the risk level of drug treatment status. This paper tried to provide a methodological paradigm for scientific and objective evaluation on the safety of Chinese patent medicines, and help to identify the key links and risk prevention in the rational use by Chinese medicine physicians and pharmacists.

Effects of aconitine poisoning and Shuang-huang-lian treatment on the expression of myocardial ryanodine receptor

To study the impact of aconitine and Shuang-huang-lian injection on the expression of myocardial ryanodine receptor (RyR2) and to discuss the anti-arrhythmic mechanisms of Shuanghuanglian against aconitine poisoning. A total of 52 SD rats were randomly divided into 3 groups: aconitine group (group A, n=20), Shuang-huang-lian group (group B, n=20) and control group (group C, n=12). Aconitine at a dose of 0.3 mg/kg was firstly administrated to the rats of group A and group B through gavage. 30 minutes later, normal saline was delivered to rats in group A through intraperitoneal injection, while rats in group B received Shuang-huang-lian at a dose of 100 mg/kg through intraperitoneal injection. Group C accepted twice administration of normal saline by gavage and intraperitoneal injection. The disposals for each group were implemented for 10 consecutive days. The rats' electrocardiograms (ECG) were recorded on day 1, 3, 6 and 10. Immunofluorescent staining technique and real-time quantitative PCR technique was used to detect the protein and mRNA expression of myocardial RyR2. The arrhythmia scores of group B at different time were lower than group A and the difference was statistically significant (P<0.05 or P<0.01). The protein and mRNA expression of RyR2 in group A was slightly increased on the first day compared to group B and group C, with no statistical significance (P>0.05). On day 3, 6 and 10, the expression of RyR2 protein and mRNA in group A was dramatically increased compared to group B and group C (P<0.01). Shuang-huang-lian injection can effectively prevent the arrhythmia caused by aconitine, which is related to suppressing the aconitine-induced RyR2 expression.

Serum concentrations of diterpenoid alkaloids after oral administration of powdered processed aconite root

The aconite tuber, which is processed from the roots of a flowering plant commonly known as monkshood, is used clinically for its analgesic, thermal, metabolic, cardiac, and diuretic effects [1]. The aconite tuber contains diterpenoid alkaloids, including aconitine, mesaconitine, hypaconitine, and jesaconitine, and mesaconitine plays a central role in the analgesic effects of this tuber [2]. Powdered aconite root is subjected to toxicity-reducing procedures that are collectively termed “processing.” It is believed that Aconitum alkaloids cannot be detected in the serum of patients who receive Chinese herbal medicines containing processed aconite root [3e6]. Previously, we developed a method to detect four types of Aconitum alkaloids in cases of aconitine poisoning, by using liquid chromatography-mass spectrometry (LC-MS) techniques, and we applied this method in a clinical setting [7e9]. Benzoylaconine, benzoylmesaconine, benzoylhypaconine, and 14-anisoylaconine are formed at the C-8 site during the toxicityreducing process following acetylic hydrolysis of Aconitum alkaloids. We previously detected four types of Aconitum alkaloids, aconitine, mesaconitine, hypaconitine, and jesaconitine, in healthy adult volunteers who were administered powdered processed aconite root containing Aconitum carmichaeli Debeaux and Aconitum japonicum Thunberg mixed at a fixed ratio [10]. Several pharmaceutical companies produce their own powdered processed aconite root products that may contain different varieties of aconite

Aconitine-induced Ca2 + overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na+ channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca2+ overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca2+ handling proteins demonstrated that aconitine promoted Ca2+ overload through the expression regulation of Ca2+ handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase.

GW24-e1714 Management of 16 cases of patients with ventricular electrical storm

ObjectivesIn the last few years awareness of ventricular electrical storm has increased. The clinical onest of ventricular electrical storm is dangerous. Electrical storm typically has a poor outcome. The mechanisms...

GW24-e1715 Clinical analysis of 19 patients with arrhythmias caused by acute aconitine poisoning

ObjectivesTo explore clinical characteristics and emergency treatment of patients with arrhythmias caused by acute aconitine poisoning.MethodsWe conducted a retrospective analysis during the period of 2010 to 2012, Clinical data of...

Fatal aconitine intoxication or thyroid storm? A case report

The case of a female in the latter half of her teens found dead in her father’s apartment is reported. A glass containing liquid and plant remnants was found at the death scene. There were no indications of any intervention or the application of force by a third party.Autopsy showed unremarkable findings. Toxicological investigations revealed lethal doses of aconitine, a highly poisonous alkaloid and the major active compound of Aconitum napellus, in all specimens. Plant remnants were identified as A. napellus leaves by a botanist and toxicological examination of the liquid in the glass on site showed extremely high concentrations of aconitine.Additionally, laboratory results revealed that the young female was suffering from thyrotoxicosis factitia, an uncommon form of hyperthyroidism caused by misuse or overdosing of thyroid hormones in order to loose weight. A rare but serious and often fatal complication of hyperthyroidism is thyroid storm.Eventually the condition of thyroid storm due to thyrotoxicosis factitia could have contributed to the woman’s death from aconitine poisoning.

Aconitine intoxication mimicking acute myocardial infarction

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.