• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.386-389
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• 2015

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

• 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.

• Journal of Veterinary Clinics
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• v.14 no.2
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• pp.319-337
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• 1997

The electrocardiographic (ECG) parameters in the normal Korean black goat have been measured with a 3-channel Electrocardiograph and computed, analyzed. ECG in 243 black goats were made with the limb leads (I, II, III, aVR, aVL, aVF), that were recorded conduction parameters of wave and interval, and were analyzed as to shape and amplitude of the P and T waves and the components of the QRS complex. Heart rate were recorded by the ECG which were a mean of 106.1$\pm $21.8 beats/min. Average conduction times in the PR, the QRS complex and the QTc interval were recorded 103.9$\pm $34.9 msec., 58.3$\pm $23.2 msec. and 302.6$\pm $67.8 msec., in the P and T wave duration recorded 24.8$\pm $6.4 msec. and 51.7$\pm $10.8 msec. respectively. The shape of wave in each leads were observed various types, and any spacial wave type appeared the highest frequency in each lead that ware shown less than 60%, and these frequent rate and average amplitudes as fallow: 1. In P waver the frequent rate and average amplitudes of the positive type showed in leads I, II and aVL that were 54.8% (93.0$\pm $ 33.2 $\mu $V), 50.5% (90.1$\pm $30.5 $\mu $V) and 41.7% (58.5$\pm $ 31.1 $\mu $V). Average amplitude of the negative type showed the frequent rate of 49.8% in lead aVE which was -77.6$\pm$ 25.2 $\mu $V. Biphasic type in leads III and aVF were 46.1% (108.4 $\mu $V, -90.2 $\mu $V.) and 45.7% (137.4 $\mu $V, -105.4 $\mu $V.), and amplitudes between positive and negative of it were significant difference. 2. The highest amplitudes of the QRS complex in all leads were 534.8$\pm $ 232.3 $\mu $V of lead II. The frequent rate and amplitudes of the R wave type in the I, II, III and aVF were 30.2% (277.8 $\pm $131.3 $\mu $V), 45.1% (393.1$\pm $114.2 $\mu $V), 48.5% (349.3$\pm $178.3 $\mu $V) and 54.9% (334.4$\pm $129.7 $\mu $V), and QS ways type in the lead aVL was 49.5% (359.2$\pm $195.5$\mu $V), and RS and QS wave types in the lead a VR were 43.3% (312.4 $\mu $V, -212.7 $\mu $V.) and 41.1% (399.2$\pm $92.2 $\mu $V), respectively. 3. In T wave, the frequent rata and amplitudes of the positive type in the leads I, II, III and aVF were 44.6% (207.9$\pm $ 97.1 $\mu $V), 41.6% (245.1$\pm $92.1 $\mu $V), 46.9% (189.8$\pm $ 82.7 $\mu $V) and 53.0% (195.4197.8 $\mu $V), and the negative in the lead aVR was 41.2% (-230.7$\pm$ 103.1 $\mu $V), respectively. The positive and negative types in the lead aVe appeared with same frequent rate of 43.2%.4. Frontal plane vectors for P, QRS, and T were found to lie at 38.1$\pm $ 21.5, 142.0$\pm $ 57.2, and 117.2$\pm $ 63.9 degrees, respectively. These results in ECG of goats may be served to the limited purposes as to conduction parameters, arrhythmias except abnormal ECG because of waveforms, amplitudes and electrical axis of it were variability.

• Korean Journal of Veterinary Research
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• v.33 no.4
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• pp.719-734
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• 1993

The electrocardiographic(ECG) parameters on the standard limb leads in the normal Korean native cattle have been measured with a 3 channel Electrocardiograph built in a computed analysis. The study was conducted on the animals 98 heads of mean age of 17.7 months. Conduction parameters, waves, intervals and segments have been recorded. The recordings were analyzed as to shape and amplitude of the P and T waves and the components of the QRS complex. Heart rate was recorded by the Electrocardiogram which were a mean of $80.4{\pm}11.6beats/min$. And the younger had a higher heart rate than the older one. Average conduction times in the RP, the QRS complex and the QTc interval recorded $166.7{\pm}23.1msec.$, $79.7{\pm}8.8msec.$ and $395.5{\pm}30.4msec.$, in the P and T wave duration recorded $70.1{\pm}13.5msec.$ and $97.6{\pm}16.9msec.$, and in the PR and ST segment duration recorded $97.9{\pm}23.5msec.$ and $173.9{\pm}40.3msec.$, respectively. The wave forms in each lead observed various types. The amplitudes of wave type showed the highest frequency in each lead that were analyzed as follow : 1. In P wave, amplitudes of the positive type showed the frequency of 65.3%, 82.7% and 52.0% in leads I, II and III that were $103.1{\pm}47.8{\mu}V$, $115.2{\pm}37.3{\mu}V$ and $67.4{\pm}26.9{\mu}V$, and it showed the frequency of 54.1% and 85.7% in the leads aVL and aVF that were $63.7{\pm}23.0{\mu}V$, $88.0{\pm}83.6{\mu}V$, respectively. Average amplitude of the negative type showed the frequency of 78.6% in lead aVR which was $99.3{\pm}38.0{\mu}V$. 2. Average amplitude of the QRS complex were from $362.8{\pm}177.7{\mu}V$ to $532.8{\pm}253.9{\mu}V$(mean of $449.1{\pm}57.2{\mu}V$) that in all leads except lead I were manifested the Low-Voltage QRS complex(below 0.5mV). Average amplitudes of each wave type in the QRS complex aere $-50.2.4{\pm}258.2{\mu}V$ and $-428.6{\pm}195.1{\mu}V$ in the QS groups type that showed a frequency of 66.3%, 70.4% in the leads I and aVL, were $451.1{\pm}20.4.0{\mu}V$, $387.6{\pm}175.8{\mu}V$ and $299.3{\pm}146.5{\mu}V$ in the R groups type that showed a frequency of 48.0%, 53.1% and 34.7% in the leads III, aVR and aVF, and were $-307.5{\pm}180.3{\mu}V$, $201.4{\pm}77.2{\mu}V$ in the QR wave type which showed a frequency of 39.8% in lead II, respectively. 3. In T wave, amplitude of the positive type showed the frequency of 50.0%, 82.7%, 51.0% and 57.1% in leads II, III aVR and aVF which were $214.9{\pm}115.6{\mu}V$, $188.5{\pm}119.3{\mu}V$, $191.0{\pm}93.7{\mu}V$ and $165.7{\pm}91.9{\mu}V$, and the negative type showed a frequecny of 66.3% and 72.5% in leads I and aVL. that were $221.3{\pm}112.5{\mu}V$, $-173.6{\pm}86.7{\mu}V$, respectively. 4. Amplitude of ST segment in leads I, II and III were a mean of $-12.2{\pm}37.2{\mu}V$, $17.5{\pm}42.6{\mu}V$ and $28.3{\pm}40.4{\mu}V$, in leads aVR, aVL and aVF were $-3.9{\pm}32.5{\mu}V$, $-15.9{\pm}35.6{\mu}V$ and $26.2{\pm}37.5{\mu}V$, respectively.