• The Korean Journal of Nuclear Medicine
• /
• v.38 no.5
• /
• pp.331-337
• /
• 2004

Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MIBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with I-123 MIBG imaging nay be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.

• Journal of Oral Medicine and Pain
• /
• v.43 no.3
• /
• pp.61-69
• /
• 2018

Obstructive sleep apnea (OSA) is a relatively common, but greatly underdiagnosed sleep-related breathing disorder, characterized by recurrent collapse of the upper airway during sleep. OSA has been associated with a variety of cardiometabolic disease, such as hypertension, coronary artery disease, cardiac arrhythmia, cerebrovascular disease and metabolic dysfunction. Neurocognitive impairment, including excessive daytime sleepiness, increased risk of motor vehicle accidents, is also related to OSA. Sleep fragmentation and related arousals during sleep lead to intermittent hypoxia, sympathetic activation, oxidative stress, systemic inflammation and metabolic dysregulation which provide biological plausibility to this pathologic mechanism. Extensive studies demonstrated that OSA is a modifiable risk factor for the above mentioned diseases and oral appliances (OAs), although continuous positive air pressure (CPAP) is a first-line therapy of OSA, are not inferior to CPAP at least in mild OSA, and may be an alternative to CPAP in CPAP-intolerant subjects with OSA. The goal of this article is to provide a current knowledge of pathologic link between OSA and cardiovascular disease, focusing on intermittent hypoxia, sympathetic activation, oxidative stress and metabolic dysregulation. Then, previous epidemiologic studies will be reviewed to understand the causal relationship between OSA and cardiovascular disease. Finally, the effects of OAs will be updated via recent metaanalyses compared to CPAP.

• Journal of Ginseng Research
• /
• v.44 no.5
• /
• pp.717-724
• /
• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

• Applied Microscopy
• /
• v.27 no.2
• /
• pp.121-130
• /
• 1997

It has been demonstrated that majority of cells in the mammalian body such as myocytes and epithelial cells of skin and intestine respond to mechanical force or environmental factors and exhibit partial disruption of cell membrane, i. e., cell wounding, even in a physiological condition. Myocardial cells are rather apt to be wounded than other cells since they are definitely exposed to mechanical stress by contraction-relaxation and blood flow. However, the mechanism how myocardial cells protect themselves against cell wounding is not yet clarified. On this background, the present study was performed to elucidate whether albumin leakage is related to cell wounding and to assess whether diltiazem, a potent calcium channel blocker, is beneficial in isoproterenol-induced cell wounding in the heart. Hearts isolated from New Zealand White rabbits ($1.5\sim2.0kg$ body weight, n=20) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to bolus administration of isoproterenol and diltiazem as following order: $1.6{\mu}M$ isoproterenol at zero min (the beginning point): $16{\mu}M$ diltiazem at 20min; $1.6{\mu}M$ isoproterenol at 25min; $16{\mu}M$ isoproterenol at 45 min; $160{\mu}M$ diltiazem at 65 min; $16{\mu}M$ isoproterenol at 70 min. During all experiments, the left ventricular function was recorded, albumin leakage in the coronary effluents was analyzed by electrophoresis and Western blot, and myocardial cell membranes were examined by conventional transmission electron microscopy. Data were analyzed by t-test and linear regression test. Isoproterenol significantly increased the inotropic and chronotropic contractions, coronary flow, and frequency of arrhythmia, however, diltiazem did not influence on hemodynamics except decrease in the frequency of arrhythmia and a slight decrease in contractility. Isoproterenol also resulted partial disruption of myocardial cell membrane and inclose in albumin leakage, while diltiazem pretreatment showed number of electron-dense plaques in the cell membrane and a tendency of decrease in albumin leakage. These results indicate that albumin leakage may be an indirect index of cell wounding in the heart and diltiazem nay be beneficial to protect myocardial cells against isoproterenol-induced cell wounding. It is likely that diltiazem promotes resealing process of the cell membrane.

• Biomolecules & Therapeutics
• /
• v.18 no.4
• /
• pp.448-453
• /
• 2010

Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG $K^+$ channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an $IC_{50}$ of 0.43 ${\mu}M$. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.

• Journal of Chest Surgery
• /
• v.41 no.5
• /
• pp.636-639
• /
• 2008

An abnormal origin of the right coronary artery can be responsible for sudden death, myocardial ischemia, arrhythmia and syncope, and it may be associated with the accelerated development of atherosclerotic disease. The mechanisms of ischemia in the case of an abnormal origin of the right coronary artery are currently unclear and several surgical methods have been proposed to treat this malady. Multidetector Computed Tomography shows the course of the abnormal coronary artery, it helps to clarify the mechanism of the ischemia and it aids in choosing the best surgical approach. We report here on a case of acute myocardial infarction with an abnormal origin of the right coronary artery. Coronary artery bypass grafting was subsequently carried out to treat this patient.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.1
• /
• pp.75-82
• /
• 2017

The effects of acepromazine on human ether-$\grave{a}$-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an $IC_{50}$ value of $1.5{\mu}M$ and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV. Before and after application of acepromazine, the half activation potentials of hERG currents changed to hyperpolarizing direction. Acepromazine blocked both the steady-state hERG currents by depolarizing pulse and the peak tail currents by repolarizing pulse; however, the extent of blocking by acepromazine in the repolarizing pulse was more profound than that in the depolarizing pulse, indicating that acepromazine has a high affinity for the open state of the channels, with a relatively lower affinity for the closed state of hERG channels. A fast application of acepromazine during the tail currents inhibited the open state of hERG channels in a concentration-dependent. The steady-state inactivation of hERG currents shifted to the hyperpolarized direction by acepromazine. These results suggest that acepromazine inhibits the hERG channels probably by an open- and inactivated-channel blocking mechanism. Regarding to the fact that the hERG channels are the potential target of drug-induced long QT syndrome, our results suggest that acepromazine can possibly induce a cardiac arrhythmia through the inhibition of hERG channels.

• Proceedings of the Acoustical Society of Korea Conference
• /
• spring
• /
• pp.269-273
• /
• 1999

Combination of mental stress task with noise background is a traditional tool employed in psychophysiology. However, intensity of background noise is a factor affecting both performance on test and psychophysiological responses associated with stress evoked by mental load in noisy environment. In the current study on 7 subjects we analyzed the influence of white noise (WN) intensity (55, 70, and 85 dB[A] ) on psychophysiological responses during word recognition test performed on noise background. There were recorded following physiological variables: electrodermal activity (EDA) , namely, skin conductance level (SCL), skin conductance response (SCR) amplitude (SCR-A), rise time and total number of SCRs (N-SCR); cardiovascular activity, e.g., heart rate (HR), respiratory sinus arrhythmia (RSA) index, pulse transit time (PTT), finger pulse volume (PV), skin temperature (SKT) and respiratory activity, such as respiration rate (RESP-R) and inspiration wane amplitude (RESP-A) during baseline resting state and 40 s long performance on 3 similar Korean word recognition tests with different WN intensity (55, 70, and 85 dB). Electrodermal responses (SCR-A, SCL, N-SCR) demonstrated gradual increment with increased intensity of noise, and this increase of response magnitude with higher intensity of noise was typical also for r skin temperature (phasic SKT decrease) and pulse volume (phasic and tonic PV decrease). However, some cardiovascular and respiratory responses did not exhibit same tendency of gradual increase of reactivity , namely HR, as well as RESP-R and RESP-A showed decrement of response magnitudes. Important finding in terms of cardiovascular reactivity was that 55 and 70dB evoked similar profiles, while 85dB WN resulted in significantly different profile of reactions, suggesting that there exists a threshold level after which intensive auditory stimulation elicits psychophyslological responses pattern of different quality. There are discussed potential autonomic mechanism involved in mediation of observed physiological responses.

• Journal of Chest Surgery
• /
• v.26 no.2
• /
• pp.75-79
• /
• 1993

Myocardial protection against ischemic and reperfusion injuries is still in troublesome eventhough couples of the way of myocardial protection have been applied since 1970's. One of the possibility in myocardial protection is adding Fructose-l,6-diphosphate(FDP) in cardioplegic solution. It is assumed that FDP can promote ATP production under anaerobic condition as well as inhibiting the supressing effect of lactate on phosphofructokinase. We compared the myocardial protecting effects of FDP in crystalloid cardioplegic solution (St. Thomas formula, 10$^{\circ}C$, pH = 7.4) and reperfusate using isolated rat hearts in modified Langendorf apparatus by the parameters of preischemic and post reperfusing heart rate, time to first beat, occurance of arrhythmia, time to stabilization, and the rate of left ventricular pressure developing. Group A (n = 10), containing no FDP in cardioplegic and reperfusing solutions was control. Group B (n = 5), containing FDP in cardioplegic solution, showed statistically significant superiority of postischemic left ventricular pressure development than the control group. Group C (n = 5), containing FDP in reperfusate, showed statistically significant myocardial depressing effect than the controls. Other parameters were unremarkable. The cause is uncertain, but it is assumed that the negative feedback inhibition of FDP in energy metabolism or unknown blocking effect of FDP on certain transmembrane ionic currents is present. In conclusion, 1) FDP in cardioplegic solution has beneficial effect on postischemic left ventricular preservation. 2) FDP is strong acid when is hydrolyzed, so precise acid titration is neccessary. 3) FDP in reperfusate has negative left ventricular preservation, otherwise the mechanism is still uncertain.

• Proceedings of the KOSOMBE Conference
• /
• v.1997 no.11
• /
• pp.222-227
• /
• 1997

To diagnose cardiac arrhythmia owing to reentry mechanism, cardiac conduction system was modeled by modified Hidden Markov modeled by evaluated. First, simulation of transient conduction states and output waves were made with initially assumed parametric values of cardiac muscle repolariztion time, conduction velocity and its automaticity. The output was a series of onset time and the name of the wave. Parameters determined the rate of beating, lengths of wave intervals, rate of abnormal beats, and the like. Several parameter sets were found to simulate normal sinus rhythm, supraventricular /ventricular tachycardia, atrial /vetricular extrasystole, etc. Then, utilizing the estimation theorems of Hidden Markov Model, the best conduction path was estimated given the previous output. With this modified estimation method, close matching between the simulated conduction path and the estimated one was confirmed.