• Journal of The Korean Society of Clinical Toxicology
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• v.10 no.2
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• pp.103-110
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• 2012

Purpose: The aim of this study was to evaluate the cardiovascular manifestations and clinical course in patients with acute carbon monoxide poisoning. Methods: A retrospective study was conducted over a 36 month period on consecutive patients who visited an emergency medical center and were diagnosed with acute carbon monoxide poisoning. A standardized data extraction protocol was performed on the selected patients. Results: A total of 293 patients were selected during the study period. Cardiac manifestations were observed in 35.2% (n=103) of the patients: hypotension in 11 patients (3.8%), ECG abnormalities in 44 patients (15.0%) and cardiac enzyme abnormalities in 103 patients (35.2%). Echo cardiography was performed on 56 patients with cardiac toxicity: 12 patients had abnormal results (5 patients with global hypokinesia and 7 patients with regional wall akinesia). Five patients died within 3 hours after ED admission, and the remaining patients were discharged alive. At 3 months after discharge, none of these patients had died.The SOFA scores in the severe cardiac toxicity group and non-severe cardiac toxicity group at the time of arrival were $2.53{\pm}2.29$ and $2.19{\pm}2.12$, respectively (p=0.860). Conclusion: Cardiovascular manifestations occur after acute CO poisoning at arateof 35.2%. Even those with severe cardiovascular toxicity recovered well within 10 days after admission. Therefore, the importance of cardiac toxicity after acute CO poisoning is not significant in itself in the clinical course, and the short-term prognosis of cardiac toxicity is unlikely to be unfavorable in acute CO poisoning.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.1
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• pp.20-25
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• 2011

Purpose: This study was designed to analyze the contributing factors, as well as the incidence and nature of the cardiac toxicity, in patients presenting with diphenhydramine overdose. Methods: We retrospectively reviewed the medical records of the intoxicated patients who presented to the ED of Korea University Anam Hospital from January 2008 to December 2010. Those patients who visited due to a diphenhydramine overdose were selected and the following features were recorded for analysis: the general characteristics, vital signs, the amount of ingested diphenhydramine, the time interval from ingestion to presentation, the coingested drugs (if any), the toxicities and the ECG findings. Cardiac toxicity, while defined mainly in terms of the temporary ECG changes such as QTc prolongation, right axis deviation, QRS widening, high degree AV block and ischemic changes, also encompassed cardiogenic shock, which is a clinical finding. Results: A total of eighteen patients were enrolled. Of the eighteen patients, eight had ingested diphenhydramine only, while ten had ingested other drugs in addition to diphenhydramine. The most commonly observed toxicity following diphenhydramine overdose included cardiac toxicity (78%). Cardiac toxicity was observed in all the patients who presented to the emergency department 2 hours after ingestion. The patients with QTc prolongation turned out to have ingested significantly larger amounts of diphenhydramine. Conclusion: QTc prolongation and right axis deviation were common findings for the patients with a diphenhydramine overdose. QTc prolongation was more likely to occur with ingesting larger amounts of diphenhydramine. Close monitoring is mandatory for patients who have ingested large amounts of diphenhydramine to prevent such potentially lethal cardiac toxicity.

• Journal of The Korean Society of Clinical Toxicology
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• v.8 no.2
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• pp.97-105
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• 2010

Purpose: Although cardiac toxicity is a key parameter of significant toxicity, in antidepressant intoxication, there are few studies on the cardiac toxicity of serotonin reuptake inhibitor and the intoxication with the new generation of antidepressants. The aim of this study is to investigate the relative cardiac toxicity of serotonin reuptake inhibitor and intoxication with the new generation of antidepressants as compared with that of tricyclic antidepressant intoxication. Methods: We retrospectively reviewed the medical records of 109 antidepressant intoxicated patients who visited the Emergency Department from January, 2005 to December, 2009 to collect and analyze the demographic and clinical data. Sixteen patients were excluded. The enrolled seventy eight patients were classified into three groups: the tricyclic antidepressant group (TCA) (n=32), the selective serotonin reuptake inhibitor subgroup (SSRI) (n=28) and the new generation antidepressant subgroup (NGA) (n=18). Results: The demographic and clinical data of the SSRI and NGA groups were not significantly different from that of the TCA group. The QRS duration of the SSRI subgroup ($86.4{\pm}12.0$ msec) and the NGA subgroup ($91.8{\pm}11.9$ msec) was not significantly different from that of the TCA group ($90.0{\pm}13.5msec$) (p=0.598). The QTc interval of the SSRI group ($444.5{\pm}33.5msec$) and the NGA group ($434.9{\pm}35.9msec$) (p=0.260) were not significantly different from that of the TCA group ($431.2{\pm}44.1msec$) (p=0.287). Conclusion: Intoxication with SSRI and the new generation antidepressants seemed to show significant cardiac toxicity, like what is seen in tricyclic antidepressant intoxication. Clinicians must pay attention to SSRI and new generation antidepressant intoxication.

• The Journal of Korean Medicine
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• v.32 no.5
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• pp.126-133
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• 2011

Objective: We report a case of non-specific Aconiti Tuber poison complaining only of severe peripheral neurotoxicity without cardiac dysfunction. Methods: The authors evaluated the symptom changes of a patient who was hospitalized in an Oriental hospital for fourteen days. The patient received acupuncture, herbal medicine, moxibustion and analgesics. Result: No abnormality in examination for cardiac function or biochemical parameters was present. The severity of pain and dysesthesia in lower extremities gradually receded during the period of treatment with herbal and western medicines. Conclusion: This study provides helpful information for treatment of Aconiti Tuber toxicity.

• Herbal Formula Science
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• v.10 no.1
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• pp.131-142
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• 2002

The effect of Banhasasim-tang extracts on the cardiac toxicity and general symptom induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. The changes of body weight, clinical signs, necropsy findings and organ weights of heart were observed. The results were as followed. 1. Decrease of body weight after Doxorubicin treatment were dose-dependently inhibited by Banhasasim-tang extracts. 2. The degrees of anorexia, ataxia and dehydration that were observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. 3. Increase of absolute and relative heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition. the degrees of heart congestion and enlargement were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. In conclusion, the toxicity of Doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of heart) was inhibited and/or prevented by Banhasasim-tang extracts. According to these results. it is considered that Banhasasim-tang has some preventive effect against to toxicity induced by Doxorubicin.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• Journal of Sensor Science and Technology
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• v.31 no.1
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• pp.6-11
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• 2022

To date, various techniques have been utilized to assess the contractility of cardiomyocytes and their response to drug-induced toxicity. However, these techniques are either invasive or involve complex fabrication methods and expertise. Here, we introduce the use of video-based analysis software to track the motion of cardiomyocytes and assess their contractility. The software, called "Tracker", is freely available and this is the first attempt at using it for cardiac contractility measurement. We used the software to measure the contractile properties of cells cultured on a rigid substrate and two flexible polydimethylsiloxane (PDMS) substrates having different elastic moduli day-wise up to eight days. Contractility was found to be highest in the most flexible substrate. Subsequently, the cardiotoxicity response of the cells on three different substrates was analyzed with verapamil. It was observed that the cells on rigid substrate were primarily affected by drug-induced toxicity, while the drug had a lesser impact on cells on the more flexible PDMS substrate. Evidently, the flexible substrate aided the maturation of cells and had lower drug toxicity, while the cells on PS could not fully mature. The assessment of cardiomyocytes using "Tracker" proved to be simple and reliable.

• Journal of The Korean Society of Clinical Toxicology
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• v.5 no.1
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• pp.74-78
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• 2007

The carbamates are a group of insecticides derived from carbamic acid, with a broad spectrum of uses as agricultural and household garden insecticides. Carbamate insecticides are reversible cholinesterase inhibitors. Their inhibitory action is mediated by reversible carbamylation of acetylcholine, as with the organophosphate insecticides. Carbamates are absorbed by the body through multiple routes, including inhalation, ingestion, and dermal absorption. Although poisoning can result from occupational exposure or accidental ingestion, in most cases there is suicidal intent. This is particularly true in developing countries, where the highest incidence of morbidity and mortality from this cause occurs. Cardiac complications often accompany poisoning by carbamate compounds, which may be serious and often fatal. The extent, frequency, and pathogenesis of cardiac toxicity from carbamate compounds has not been clearly defined. Possible mechanismsinclude sympathetic and parasymphatetic overactivity, hypoxemia, acidosis, electrolyte derangements, and a direct toxic effect of the compounds on the myocardium. Patients with carbamate poisoning should immediately be transferred to an intensive or coronary care unit where appropriate monitoring and resuscitative facilities are available. We here report a case of acute coronary syndrome resulting from acute carbamate ingestionthat resulted in a healthy discharge.

• Toxicological Research
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• v.35 no.3
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• pp.233-239
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• 2019

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.