Browsing by Author "Lin, Shien-Fong"

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A DNA Memory Translator for Multiple Languages
(2018-01-01)
Huang, Yi-Man
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Lin, Shien-Fong
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生醫工程研究所
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Institute of Biomedical Engineering
As the demand for data storage is growing exponentially, higher density and durable storage solutions are necessary. DNA has many potential advantages as a medium for information storage because it is extremely dense, high capacity, low-maintenance and durability. Previous research has focused on ASCII code files or pictures, which ignored expression with other languages encoded with Unicode. We provide a DNA translator for multiple languages and also discuss the influence of entropy in different dataset. The effect of Huffman code encoding and ternary code encoding for different dataset are also compared. Our results indicate that the DNA memory translator system is very efficient for the dataset with low entropy.
A Mixed Reality System to Improve Walking Experience
(2018-01-01)
Chao, Tz-Yang
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Lin, Shien-Fong
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交大名義發表
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National Chiao Tung University
The objective of the study is to improve walking experience with mixed reality technique. Walking is an excellent exercise, especially for the elderly. However, walking may become tedious due to limitation of the environment. Mixed reality, the hybrid of augmented reality and virtual reality, is able to turn real environment into fascinated world, and offers new opportunities to improve walking experience. In this research, a mixed reality walking system has been developed. With the function of guiding user to walk continuously in specified range and to interact with virtual characters, mixed reality provides new paradigm in improving walking experience. Concerns over user's safety and convenience in a mixed reality setting are discussed.
Accelerating sino-atrium computer simulations with graphic processing units
(2015-01-01)
Zhang, Hong
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Xiaoa, Zheng
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Lin, Shien-Fong
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分子醫學與生物工程研究所
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Institute of Molecular Medicine and Bioengineering
Sino-atrial node cells (SANCs) play a significant role in rhythmic firing. To investigate their role in arrhythmia and interactions with the atrium, computer simulations based on cellular dynamic mathematical models are generally used. However, the large-scale computation usually makes research difficult, given the limited computational power of Central Processing Units (CPUs). In this paper, an accelerating approach with Graphic Processing Units (GPUs) is proposed in a simulation consisting of the SAN tissue and the adjoining atrium. By using the operator splitting method, the computational task was made parallel. Three parallelization strategies were then put forward. The strategy with the shortest running time was further optimized by considering block size, data transfer and partition. The results showed that for a simulation with 500 SANCs and 30 atrial cells, the execution time taken by the non-optimized program decreased 62% with respect to a serial program running on CPU. The execution time decreased by 80% after the program was optimized. The larger the tissue was, the more significant the acceleration became. The results demonstrated the effectiveness of the proposed GPU-accelerating methods and their promising applications in more complicated biological simulations.
Acute reversal of phospholamban inhibition facilitates the rhythmic whole-cell propagating calcium waves in isolated ventricular myocytes
(2015-03-01)
Chan, Yi-Hsin
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Tsai, Wei-Chung
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Song, Zhen
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Ko, Christopher Y.
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Qu, Zhilin
Phospholamban (PLB) inhibits the activity of cardiac sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). Phosphorylation of PLB during sympathetic activation reverses SERCA2a inhibition, increasing SR Ca2+ uptake. However, sympathetic activation also modulates multiple other intracellular targets in ventricular myocytes (VMs), making it impossible to determine the specific effects of the reversal of PLB inhibition on the spontaneous SR Ca2+ release. Therefore, it remains unclear how PLB regulates rhythmic activity in VMs. Here, we used the Fab fragment of 2D12, a monoclonal anti-PLB antibody, to test how acute reversal of PLB inhibition affects the spontaneous SR Ca2+ release in normal VMs. Ca2+ sparks and spontaneous Ca2+ waves (SCWs) were recorded in the line-scan mode of confocal microscopy using the Ca2+ fluorescent dye Fluo-4 in isolated permeabilized mouse VMs. Fab, which reverses PLB inhibition, significantly increased the frequency, amplitude, and spatial/temporal spread of Ca2+ sparks in VMs exposed to 50 nM free [Ca2+]. At physiological diastolic free [Ca2+] (100-200 nM), Fab facilitated the formation of whole-cell propagating SCWs. At higher free [Ca2+], Fab increased the frequency and velocity, but decreased the decay time of the SCWs. cAMP had little additional effect on the frequency or morphology of Ca2+ sparks or SCWs after Fab addition. These findings were complemented by computer simulations. In conclusion, acute reversal of PLB inhibition alone significantly increased the spontaneous SR Ca2+ release, leading to the facilitation and organization of whole-cell propagating SCWs in normal VMs. PLB thus plays a key role in subcellular Ca2+ dynamics and rhythmic activity of VMs. (C) 2015 Elsevier Ltd. All rights reserved.
Antiarrhythmic effects of stimulating the left dorsal branch of the thoracic nerve in a canine model of paroxysmal atrial tachyarrhythmias
(2018-08-01)
Zhao, Ye
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Yuan, Yuan
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Tsai, Wei-Chung
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Jiang, Zhaolei
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Tian, Zhi-peng
BACKGROUND Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial tachyarrhythmia (PAT) episodes in dogs with intermittent rapid left atrial (LA) pacing. The left dorsal branch of the thoracic nerve (LDTN) contains sympathetic nerves originating from the stellate ganglia. OBJECTIVE The purpose of this study was to test the hypothesis that high-frequency electrical stimulation of the LDTN can cause stellate ganglia damage and suppress PATs. METHODS We performed long-term LDTN stimulation in 6 dogs with and 2 dogs without intermittent rapid LA pacing while monitoring SGNA. RESULTS LDTN stimulation reduced average SGNA from 4.36 mu V (95% confidence interval [CI] 4.10-4.62 mu V) at baseline to 3.22 mu V (95% CI 3.04-3.40 mu V) after 2 weeks (P5.028) and completely suppressed all PAT episodes in all dogs studied. Tyrosine hydroxylase staining showed large damaged regions in both stellate ganglia, with increased percentages of tyrosine hydroxylase-negative cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that 23.36% (95% CI 18.74%-27.98%) of ganglion cells in the left stellate ganglia and 11.15% (95% CI 9.34%-12.96%) ganglion cells in the right stellate ganglia were positive, indicating extensive cell death. A reduction of both SGNA and heart rate was also observed in dogs with LDTN stimulation but without rapid LA pacing. Histological studies in the 2 dogs without intermittent rapid LA pacing confirmed the presence of extensive stellate ganglia damage, along with a high percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. CONCLUSION LDTN stimulation damages both left and right stellate ganglia, reduces left SGNA, and is antiarrhythmic in this canine model of PAT.
Apamin induces early afterdepolarizations and torsades de pointes ventricular arrhythmia from failing rabbit ventricles exhibiting secondary rises in intracellular calcium
(2013-10-01)
Chang, Po-Cheng
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Hsieh, Yu-Cheng
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Hsueh, Chia-Hsiang
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Weiss, James N.
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Lin, Shien-Fong
BACKGROUND A secondary rise of intracellular Ca2+ (Ca) and an upregulation of apamin-sensitive K+ current (I-KAs) are characteristic findings of failing ventricular myocytes. We hypothesize that apamin, a specific IKAs Mocker, may induce torsades de pointes (TdP) ventricular arrhythmia from failing ventricles exhibiting secondary rises of Ca,. OBJECTIVE To test the hypothesis that small conductance Ca2+ activated Los maintains repolarization reserve and prevents ventricular arrhythmia in a rabbit model of heart failure (HF). METHODS We performed Langendorff perfusion and optical mapping studies in 7 hearts with pacing-induced HF and in 5 normal control rabbit hearts. Atrioventricular block was created by cryoablation to allow pacing at slow rates. RESULTS The left ventricular ejection fraction reduced from 69.1% [95% confidence interval 62.3%-76.0%] before pacing to 30.4% [26.8%-34.0%] (N = 7; P <.001) after pacing. The corrected QT interval in failing ventricles was 337 [313-360] ms at baseline and 410 [381-439] ms after applying 100 nmol/L of apamin (P = .01). Apamin induced early afterdepolarizations (EADs) in 6 ventricles, premature ventricular beats (PVBs) in 7 ventricles, and polymorphic ventricular tachycardia consistent with TdP in 4 ventricles. The earliest activation site of EADs and PVBs always occurred at the site with long action potential duration and large amplitude of the secondary rises of Ca,. Apamin induced secondary rises of Ca, in 1 nonfailing ventricle, but no EAD or TdP were observed. CONCLUSIONS In HF ventricles, apamin induces EADs, PVBs, and TdP from areas with secondary rises of Ca,. IKAs is important in maintaining repolarization reserve and preventing TdP in HF ventricles.
Concomitant SK current activation and sodium current inhibition cause J wave syndrome
(2018-11-15)
Chen, Mu
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Xu, Dong-Zhu
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Wu, Adonis Z.
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Guo, Shuai
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Wan, Juyi
The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (I-KAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. I-KAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (I-Na) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent I-KAS blockade by apamin reduced J wave elevation and eliminated SVF. beta-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0 degrees C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that I-KAS activation contributes to the development of JWS in rabbit ventricles.
Design and Construction of an Intelligent Stacking Cone Upper Limb Rehabilitation System
(2018-01-01)
Chiu, Ya-Hui
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Yen, San-Feng
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Lin, Shien-Fong
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分子醫學與生物工程研究所
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Institute of Molecular Medicine and Bioengineering
Stroke patients, due to lack of exercise, usually suffer from muscle atrophy or functional deterioration. Therefore the patients need to do long-term rehabilitation therapy activities. The current clinical practice uses static rehabilitation tools such as stacking cones without immediate functional feedback. During the procedure, an occupational therapist (OT) fills out a Brunnstrom stage form to evaluate the status of upper limb. This approach has not been effective because patients may feel tired and boring with these tools. According to Brunnstrom stage, the palm grip ability level between three to six, and the arm strength level between four to six can use stacking cones for rehabilitation purposes. The research methods in this project are based on the patients' need to do rehabilitation with stacking cones, such as those with stroke, spinal cord injury, brain injury, Parkinson's disease, hand and visual perception problems. This study aims to establish a smart stacking cones device for upper limb rehabilitation with evaluation function. The goal is to raise the efficacy and add fun level during diagnostic and therapeutic procedures, therefore to achieve improved upper limb action, palm grip action, strength, endurance, coordination and other capabilities.
Development of a Novel Heart Rate Synchronized Pulsatile Left Ventricular Assist Device
(2018-01-01)
Liu, Chun
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Fang, Jia-Ching
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Yeh, Chi-Hsiao
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Lin, Shien-Fong
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分子醫學與生物工程研究所
The left ventricular assist device (LVADs) have been used as either a bridge to transplant or destination therapy for end stage heart failure. The continuous-flow models have been used with multiple complications. This project applied electromagnetically driven pump to the development of a heart-rate synchronized pulsatile LVAD. A control system was developed based on LabVIEW programming platform. The LabVIEW program receives pulse signals by DAQ device and then output the signal to control the coil of the pump by DAQ device. Under the action of the magnetic effect of electric current, thus the magnetic piston inside the pump is pushed back and forth. The program not only receives pulse signals but also synchronizes the pump and pulsation. The researchers used heart mock to test the flow situation of water. According to the current situation, the pump can affect the water flow. Currently, the experiment enters the stage that cooperates with Keelung Chang Gung Memorial Hospital. In addition, the circuit is miniaturized and the connector is used for experimental convenience in the hospital in the future.
Differential effects of SKCa blockade on arrhythmogenesis in normal and remodeled hearts
(2015-01-01)
Hsueh, Chia-Hsiang
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Chen, Peng-Sheng
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Lin, Shien-Fong
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分子醫學與生物工程研究所
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Institute of Molecular Medicine and Bioengineering
Effects of high-frequency biphasic shocks on ventricular vulnerability and defibrillation outcomes through synchronized virtual electrode responses
(2020-05-01)
Chiou, Yu-An
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Cheng, Li-Kuan
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Lin, Shien-Fong
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交大名義發表
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National Chiao Tung University
Electrical defibrillation is a well-established treatment for cardiac dysrhythmias. Studies have suggested that shock-induced spatial sawtooth patterns and virtual electrodes are responsible for defibrillation efficacy. We hypothesize that high-frequency shocks enhance defibrillation efficacy by generating temporal sawtooth patterns and using rapid virtual electrodes synchronized with shock frequency. High-speed optical mapping was performed on isolated rat hearts at 2000 frames/s. Two defibrillation electrodes were placed on opposite sides of the ventricles. An S1-S2 pacing protocol was used to induce ventricular tachyarrhythmia (VTA). High-frequency shocks of equal energy but varying frequencies of 1251000 Hz were used to evaluate VTA vulnerability and defibrillation success rate. The 1000Hz shock had the highest VTA induction rate in the shorter S1-S2 intervals (50 and 100 ms) and the highest VTA defibrillation rate (70%) among all frequencies. Temporal sawtooth patterns and synchronous shock-induced virtual electrode responses could be observed with frequencies of up to 1000 Hz. The improved defibrillation outcome with high-frequency shocks suggests a lower energy requirement than that of low-frequency shocks for successful ventricular defibrillation.
Effects of long-term exercise on arrhythmogenesis in aged hypertensive rats
(2018-11-01)
Sung, Yen-Ling
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Wu, Chih-En
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Syu, Jhen-Yang
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Kuo, Terry B. J.
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Li, Jai-Yi
Chronic hypertension is a multifactorial disease that is highly associated with cardiovascular disorders. Physical activity, such as long-term exercise, is advocated as a treatment for hypertension, but the responses of different age groups to long-term exercise are unknown. We used aged spontaneous hypertensive rats (SHRs, 80 weeks old) to test the hypothesis that long-term exercise compensated for deficient autonomic control and reduced susceptibility to ventricular tachycardia (VT) and ventricular fibrillation (VF) in this animal model. The aged SHRs were divided into control and voluntary exercise groups. Ambulatory electrocardiography was recorded for the heart rate variability (HRV) analysis. Programmed stimulation was applied to exposed hearts to induce ventricular arrhythmia in situ. Then, the hearts were isolated for an optical mapping study. The results showed that increased HRV indices were broadly related to vagal dominance in the high-intensity exercise group. Exercise altered the electrical propagation dynamic properties, such as the action potential duration restitution (APDR). Furthermore, the VF inducibility decreased with increased exercise intensity. Taken together, our results suggest that long-term exercise reduces the risk of arrhythmogenesis in aged SHRs through enhanced vagal control and stabilized electrical dynamics.
Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts
(2020-02-01)
Yin, Dechun
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Yang, Na
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Tian, Zhipeng
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Wu, Adonis Z.
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Xu, Dongzhu
BACKGROUND Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (I-KAS). OBJECTIVE The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by I-KAS inhibition. METHODS Optical mapping was performed in rabbit hearts with pacing-induced heart failure (HF) and in normal hearts before and after ondansetron (100 nM) infusion. APD at 80% repolarization (APD(80)) and arrhythmia inducibility were determined. Additional studies with ondansetron were performed in normal hearts perfused with hypokalemic Tyrode's (2.4 mM) solution before or after apamin administration. RESULTS The corrected QT interval in HF was 326 ms (95% confidence interval [CI] 306-347 ms) at baseline and 364 ms (95% CI 351-378 ms) after ondansetron infusion (P < .001). Ondansetron significantly prolonged APD(80) in the HF group and promoted early afterdepolarizations, steepened the APD restitution curve, and increased ventricular vulnerability. Ventricular fibrillation was not inducible in HF ventricles at baseline, but after ondansetron infusion, ventricular fibrillation was induced in 5 of the 7 ventricles (P = .021). In hypokalemia, apamin prolonged APD(80) from 163 ms (95% CI 146-180 ms) to 180 ms (95% CI 156-204 ms) (P = .018). Subsequent administration of ondansetron failed to further prolong APD(80) (180 ms [95% CI 156-204 ms] vs 179 ms [95% CI 165-194 ms]; P = .789). The results were similar when ondansetron was administered first, followed by apamin. CONCLUSION Ondansetron is a specific I-KAS blocker at therapeutic concentrations. Ondansetron may prolong the QT interval in HF by inhibiting small conductance calcium-activated potassium channels, which increases the vulnerability to ventricular arrhythmias.
Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs
(2017-02-01)
Tsai, Wei-Chung
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Chan, Yi-Hsin
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Chinda, Kroekkiat
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Chen, Zhenhui
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Patel, Jheel
BACKGROUND Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. OBJECTIVE We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. METHODS We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 +/- 4.0, 9.3 +/- 2.8, and 9.6 +/- 2.0 mu V, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% +/- 10% and 40% +/- 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. CONCLUSION Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.
Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart
(2018-03-01)
Rubart, Michael
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Tao, Wen
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Lu, Xiao-Long
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Conway, Simon J.
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Reuter, Sean P.
Recent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts. We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction. Transgenic mice with cardiomyocyte-restricted expression of a green fluorescent reporter protein underwent permanent coronary artery ligation and their hearts were subjected to voltage imaging 7-10 days later. Reporter-negative cells, i.e. nonmyocytes, in the infarct border zone exhibited depolarizing transients at a 1:1 coupling ratio with action potentials recorded simultaneously from adjacent, reporter-positive ventricular myocytes. The electrotonic responses in the nonmyocytes exhibited slower rates of de- and repolarization compared to the action potential waveform of juxtaposed myocytes. Voltage imaging in infarcted hearts expressing a fluorescent reporter specifically in myofibroblasts revealed that the latter were electrically coupled to border zone myocytes. Their voltage transient properties were indistinguishable from those of nonmyocytes in hearts with cardiomyocyte-restricted reporter expression. The density of connexin43 expression at myofibroblast-cardiomyocyte junctions was similar to 5% of that in the intercalated disc regions of paired ventricular myocytes in the remote, uninjured myocardium, whereas the ratio of connexin45 to connexin43 expression levels at heterocellular contacts was similar to 1%. Myofibroblasts contribute to the population of electrically coupled nonmyocytes in the infarct border zone. The slower kinetics of myofibroblast voltage responses may reflect low electrical conductivity across heterocellular junctions, in accordance with the paucity of connexin expression at myofibroblast-cardiomyocyte contacts.
Estimating Sympathetic Tone by Recording Subcutaneous Nerve Activity in Ambulatory Dogs
(2015-01-01)
Robinson, Eric A.
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Rhee, Kyoung-Suk
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Doytchinova, Anisiia
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Kumar, Mohineesh
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Shelton, Richard
Subcutaneous Nerve Activity IntroductionWe tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to estimate the sympathetic tone. Methods and ResultsWe implanted radio transmitters in 11 ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA), and left thoracic SCNA, including 3 with simultaneous video monitoring and nerve recording. Two additional dogs were studied under general anesthesia with apamin injected into the right stellate ganglion while the right SGNA and the right SCNA were recorded. There was a significant positive correlation between integrated SGNA (iSGNA) and integrated SCNA (iSCNA) in the first 7 ambulatory dogs, with correlation coefficient of 0.70 (95% confidence interval [CI] 0.61-0.84, P < 0.05 for each dog). Tachycardia episodes (heart rate exceeding 150 bpm for 3 seconds) were invariably preceded by SGNA and SCNA. There was circadian variation of both SCNA and SGNA. Crosstalk was ruled out because SGNA, VNA, and SCNA bursts had different timing and activation patterns. In an eighth dog, closely spaced bipolar subcutaneous electrodes also recorded SCNA, but with reduced signal to noise ratio. Video monitoring in additional 3 dogs showed that movement was not a cause of high frequency SCNA. The right SGNA correlated strongly with right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the right stellate ganglion. ConclusionsSCNA recorded by bipolar subcutaneous electrodes correlates with the SGNA and can be used to estimate the sympathetic tone.
Ganglionated plexi and ligament of Marshall ablation reduces atrial vulnerability and causes stellate ganglion remodeling in ambulatory dogs
(2016-10)
Zhao, Ye
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Jiang, Zhaolei
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Tsai, Wei-Chung
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Yuan, Yuan
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Chinda, Kroekkiat
BACKGROUND Simultaneous activation of the stellate ganglion (SG), the ligament of Marshall (LOM), and the ganglionated plexi often precedes the onset of paroxysmal atrial tachyarrhythmia (PAT). OBJECTIVE The purpose of this study was to test the hypothesis that ablation of the LOM and the superior left ganglionated plexi (SLGP) reduces atrial vulnerability and results in remodeling of the SG. METHODS Nerve activity was correlated to PAT and ventricular rate (VR) at baseline, after ablation of the LOM and SLGP, and after atrial fibrillation. Neuronal cell death was assessed with tyrosine hydroxylase and terminal deoxynucleotidyl transferase dUTP nick end label (TUNEL) staining. RESULTS There were 4 2 PAT episodes per day in controls. None were observed in the ablation group, even though SG nerve activity and VR increased from 2.2 mu V (95% confidence interval [CI] 1.2-3.3 mu V) and 80 bpm (95% CI 68-92 bpm) at baseline, to 3.0 mu V (95% CI 2.6-3.4 mu V, P = .046) and 90 bpm (95% CI 75-108 bpm, P = .026) after ablation, and to 3.1 mu V (95% CI 1.7-4.5 mu V, P = .116) and 95 bpm (95% CI 79-110 bpm, P = .075) after atrial fibrillation. There was an increase in tyrosine hydroxylase negative cells in the ablation group and 19.7% (95% CI 8.6%-30.8%) TUN EL-positive staining in both the left and right SG. None were observed in the control group. CONCLUSION LOM and SLGP ablation caused left SG remodeling and cell death. There was reduced correlation of the VR response and PAT to SG nerve activity. These findings support the importance of SLGP and LOM in atrial arrhythmogenesis.
Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts
(2016-01-01)
Hsieh, Yu-Cheng
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Lin, Jiunn-Cherng
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Hung, Chen-Ying
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Li, Cheng-Hung
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Lin, Shien-Fong
BACKGROUND Therapeutic hypothermia (TH) may increase the susceptibility to ventricular arrhythmias by decreasing ventricular conduction velocity (CV) and facilitating arrhythmogenic spatially discordant alternans (SDA). OBJECTIVE The purpose of this study was to test the hypothesis that rotigaptide, a gap junction enhancer, can increase ventricular CV, delay the onset of SDA, and decrease the susceptibility to pacing-induced ventricular fibrillation (PIVF) during TH. METHODS Langendorff-perfused isolated rabbit hearts were subjected to 30-minute moderate hypothermia (33 degrees C) followed by 20-minute treatment with rotigaptide (300 nM, n = 8) or vehicle (n = 5). The same protocol was also performed at severe hypothermia (30 degrees C; n = 8 for rotigaptide, n = 5 for vehicle). Using an optical mapping system, epicardial CV and SDA threshold were evaluated by Si pacing. Ventricular fibrillation inducibility was evaluated by burst pacing for 30 seconds at the shortest pacing cycle length (PCL) that achieved 1:1 ventricular capture. RESULTS Rotigaptide increased ventricular CV during 33 degrees C (PCL 300 ms, from 76 +/- 6 cm/s to 84 +/- 7 cm/s, P =.039) and 30 degrees C (PCL 300 ms, from 62 +/- 6 cm/s to 68 +/- 4 cm/s, P =.008). Rotigaptide decreased action potential duration dispersion at 33 degrees C (P =.01) and 30 degrees C (P =.035). During 30 degrees C, SDA thresholds (P =.042) and incidence of premature ventricular complexes (P =.025) were decreased by rotigaptide. PIVF inducibility was decreased by rotigaptide at 33 degrees C (P =.039) and 30 degrees C (P =.042). Rotigaptide did not change connexin43 expressions and distributions during hypothermia. CONCLUSION Rotigaptide protects the hearts against ventricular arrhythmias by increasing ventricular CV, delaying the onset of SDA, and reducing repolarization heterogeneity during TH. Enhancing cell-to-cell coupling by rotigaptide might be a novel approach to prevent ventricular arrhythmias during TH.
Graphene Oxide-Based Biosensors for Liquid Biopsies in Cancer Diagnosis
(2019-12-01)
Chen, Shiue-Luen
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Chen, Chong-You
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Hsieh, Jason Chia-Hsun
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Yu, Zih-Yu
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Cheng, Sheng-Jen
Liquid biopsies use blood or urine as test samples, which are able to be continuously collected in a non-invasive manner. The analysis of cancer-related biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA, and exosomes provides important information in early cancer diagnosis, tumor metastasis detection, and postoperative recurrence monitoring assist with clinical diagnosis. However, low concentrations of some tumor markers, such as CTCs, ctDNA, and microRNA, in the blood limit its applications in clinical detection and analysis. Nanomaterials based on graphene oxide have good physicochemical properties and are now widely used in biomedical detection technologies. These materials have properties including good hydrophilicity, mechanical flexibility, electrical conductivity, biocompatibility, and optical performance. Moreover, utilizing graphene oxide as a biosensor interface has effectively improved the sensitivity and specificity of biosensors for cancer detection. In this review, we discuss various cancer detection technologies regarding graphene oxide and discuss the prospects and challenges of this technology.
Graphene Oxide-Based Nanomaterials: An Insight into Retinal Prosthesis
(2020-04-01)
Yang, Jia-Wei
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Yu, Zih-Yu
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Cheng, Sheng-Jen
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Chung, Johnson H. Y.
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Liu, Xiao
Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis.