Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals ; Humans ; Medicine, Chinese Traditional/adverse effects* ; Cardiotoxicity ; Induced Pluripotent Stem Cells ; Arrhythmias, Cardiac/chemically induced* ; Myocytes, Cardiac ; Organoids ; Drugs, Chinese Herbal/adverse effects*

OBJECTIVETo investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.

METHODSTwenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.

RESULTSCompared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.

CONCLUSIONSLPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; physiopathology ; Connexin 43 ; metabolism ; Lysophospholipids ; adverse effects ; Oligopeptides ; pharmacology ; Rabbits

Amiodarone ; adverse effects ; Anti-Arrhythmia Agents ; adverse effects ; Arrhythmias, Cardiac ; drug therapy ; Corneal Diseases ; chemically induced ; Humans ; Male ; Middle Aged

BACKGROUNDLidocaine and ropivacaine are often combined in clinical practice to obtain a rapid onset and a prolonged duration of action. However, the systemic toxicity of their mixture at different concentrations is unclear. This study aimed to compare the systemic toxicity of the mixture of ropivacaine and lidocaine at different concentrations when administered intravenously in rats.

METHODSForty-eight male Wistar rats were randomly divided into 4 groups (n = 12 each): 0.5% ropivacaine (group I); 1.0% ropivacaine and 1.0% lidocaine mixture (group II); 1.0% ropivacaine and 2.0% lidocaine mixture (group III); and 1.0% lidocaine (group IV). Local anesthetics were infused at a constant rate until cardiac arrest. Electrocardiogram, electroencephalogram and arterial blood pressure were continuously monitored. The onset of toxic manifestations (seizure, dysrhythmia, and cardiac arrest) was recorded, and then the doses of local anesthetics were calculated. Arterial blood samples were drawn for the determination of local anesthetics concentrations by high-performance liquid chromatography.

RESULTSThe onset of dysrhythmia was later significantly in group IV than in group I, group II, and group III (P < 0.01), but there was no significant difference in these groups (P > 0.05). The onset of seizure, cardiac arrest in group I ((9.2 + or - 1.0) min, (37.0 + or - 3.0) min) was similar to that in group II ((9.1 + or - 0.9) min, (35.0 + or - 4.0) min) (P > 0.05), but both were later in group III ((7.5 + or - 0.7) min, (28.0 + or - 3.0) min) (P < 0.05). The onset of each toxic manifestation was significantly later in group IV than in group I (P < 0.01). The plasma concentrations of the lidocaine-alone group at the onset of dysrhythmia (DYS), cardiac arrest (CA) ((41.2 + or - 6.8) min, (59.0 + or - 9.0) min) were higher than those of the ropivacaine alone group ((20.5 + or - 3.8) min, (38.0 + or - 8.0) min) (P < 0.05). The plasma concentrations of ropivacaine inducing toxic manifestation were not significantly different among groups I, II, and III (P > 0.05).

CONCLUSIONSThe systemic toxicity of the mixture of 1.0% ropivacaine and 2.0% lidocaine is the greatest while that of 1.0% lidocaine is the least. However, the systemic toxicity of the mixture of 1.0% ropivacaine and 1.0% lidocaine is similar to that of 0.5% ropivacaine alone.

Amides ; toxicity ; Anesthetics, Local ; toxicity ; Animals ; Arrhythmias, Cardiac ; chemically induced ; Cardiovascular System ; drug effects ; Central Nervous System ; drug effects ; Heart Arrest ; chemically induced ; Lidocaine ; toxicity ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Seizures ; chemically induced

Abstract: Suxamethonium chloride is a depolarizing muscle relaxant used in general anesthesia. In overdose, it causes adverse reactions such as bradycardia, arrhythmia, cardiac arrest, and death. The article reviews the progress on testing methods of suxamethonium chloride such as infrared spectroscopy, chemical color reaction, chemical titration, enzyme electrode, chromatography and mass spectrometry.
Anesthesia, General ; Arrhythmias, Cardiac/chemically induced* ; Biosensing Techniques ; Bradycardia/chemically induced* ; Chromatography ; Drug Overdose ; Heart Arrest/chemically induced* ; Humans ; Mass Spectrometry ; Neuromuscular Depolarizing Agents/analysis* ; Spectrophotometry, Infrared ; Succinylcholine/analysis*

Acute Disease ; Adult ; Antimalarials ; blood ; poisoning ; Arrhythmias, Cardiac ; chemically induced ; Chloroquine ; blood ; poisoning ; Death, Sudden, Cardiac ; etiology ; Drug Overdose ; complications ; Fatal Outcome ; Female ; Humans

Animals ; Arrhythmias, Cardiac ; chemically induced ; prevention & control ; Cats ; Endothelin-1 ; adverse effects ; Medulla Oblongata ; drug effects ; Metoprolol ; pharmacology ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo study the anti-arrhythmic efficacy of ginsenoside Re (GSRe) and its protective effects against myocardial injuries in rabbits with isoproterenol-induced triggered ventricular arrhythmia (TVA).

METHODSTVA model was prepared by intravenous injections of isoproterenol at a constant speed of 5 mg/kg/min. When TVA appeared, rabbits were randomly injected with GSRe (5, 10 or 20 mg/kg), verapamil (0.4 mg/kg) or placebo. The duration of maintaining sinus rhythm was observed. Meanwhile, isoproterenol was continued to be injected at a constant speed of 5 mg/kg/min. After 1 hr of isoproterenol injection, the rabbits were sacrificed. Cardiac muscles in the cuspidate position of the left ventricle were sampled for optical microscopy and electron microscopy.

RESULTSGSRe and verapamil treatment restored sinus rhythm. The duration of sinus rhythm was 177.00+/- 5.66 s within 3 minutes in the verapamil treatment group and was 177.83+/- 5.31, 21.00+/- 2.83 and 4.50+/- 1.64 s, respectively, in the 20, 10 and 5 mg/kg GSRe treatment groups. Histopathologic examination demonstrated that GSRe treatment (20 and 10 mg/kg) alleviated myocardial injuries induced by TVA.

CONCLUSIONSGSRe has anti-arrhythmic efficacies and protective effects against myocardial injuries in rabbits with TVA. It may therefore be a possible therapy for TVA.

Animals ; Arrhythmias, Cardiac ; chemically induced ; pathology ; prevention & control ; Ginsenosides ; therapeutic use ; Heart Ventricles ; drug effects ; Isoproterenol ; pharmacology ; Male ; Myocardium ; pathology ; ultrastructure ; Rabbits ; Verapamil ; therapeutic use

Animals ; Arrhythmias, Cardiac ; chemically induced ; etiology ; Female ; Heart ; drug effects ; In Vitro Techniques ; Lysophospholipids ; pharmacology ; physiology ; Male ; Random Allocation ; Rats ; Rats, Wistar

AIMTo investigate the antiarrhythmic effect of jumi (JM) extraction.

METHODSThe conventional antiarrhythmic methods were used.

RESULTSAdministration of JM extraction reduced the occurrence of ventricular fibrillation induced by chloroform in a dose-dependent manner in mice. Quinidine significantly decreased the number of ventricular premature beats and ventricular tachycardia, shortened the duration of arrhythmia in aconitine-treated rats. But JM extraction had no effect on aconitine-induced arrhythmia. Compared with control, arrhythmia score was lower in ischemia/reperfusion rats which pretreated with 2.0 g/kg of JM extraction.

CONCLUSIONJM extraction has obvious protection effects in chloroform- and ischemia-induced arrhythmia, but has no effect in aconitine-induced arrhythmia.

Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; drug therapy ; Female ; Male ; Mice ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley