My expertise and research interests lie in mathematics, artificial intelligence (AI), data science, cardiac electrophysiology, and smart healthcare. I am currently a faculty member at a university."
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MOESM1 of Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study
Additional file 1: Table S1. Hazard ratios of MACE in patients receiving different 2nd-line anti-... more Additional file 1: Table S1. Hazard ratios of MACE in patients receiving different 2nd-line anti-diabetic agents with or without ACEI/ARBs and statins. Table S2. Hazard ratios of MACE in patients receiving pioglitazone and rosiglitazone as the 2nd-line anti-diabetic agents compared to SU.
Computational modeling of human diseases is an emerging field of research interests. The methodol... more Computational modeling of human diseases is an emerging field of research interests. The methodology applied is absolutely non-invasive, producing no harm to the patient or animals, and information so obtained is useful for identifying and/or confirming the underlying pathogenetic mechanism. In this communication, we describe how modeling can recapitulate clinical features of inherited arrhythmogenic disorders of the heart. Taking Timothy syndrome (TS), a malignant form of long QT syndrome referred to as LQT8, in which patients seldom survive beyond three years of age, as an example, modeling was intended to define the mechanism by which recurrent ventricular tachyarrhythmias could be provoked by enhanced sympathetic tone (e.g., exertion and/or emotional distress) and to search for potential targeted sites for pharmacotherapy beyond beta-adrenergic blockers which clinically often fail to provide complete protection. The study used the latest state-of-the-art Luo-Rudy guinea pig vent...
Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological ... more Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm con...
Proceedings of the American Mathematical Society, 2003
We study a two-point free boundary problem for the curvature flow equation. By studying the corre... more We study a two-point free boundary problem for the curvature flow equation. By studying the corresponding nonlinear initial value problem, we obtain the existence and uniqueness of the forward self-similar solution of this problem. The corresponding curve is called the self-similar expanding curve. We also derive the asymptotic stability of this curve.
This work studies nonnegative solutions for the Cauchy, Neumann, and Dirichlet problems of a logi... more This work studies nonnegative solutions for the Cauchy, Neumann, and Dirichlet problems of a logistic type reaction-diffusion equation. The finite time blowup results for nonnegative solutions under various restrictions on the coefficients of this equation are presented. Applying the results allows one to construct some reaction diffusion systems with the so-called diffusion-induced blowup phenomenon, particularly in the case of equal diffusion rates.
Hypoglycemic Episodes Increase the Risk of Ventricular Arrhythmia and Sudden Cardiac Arrest in Patients with Type 2 Diabetes‐ A Nationwide Cohort Study
Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the ... more Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox...
Moderate Hypothermia (33 °C) Decreases the Susceptibility to Pacing-Induced Ventricular Fibrillation Compared with Severe Hypothermia (30 °C) by Attenuating Spatially Discordant Alternans in Isolated Rabbit Hearts
Severe hypothermia (SH, 30 °C) increases the risk of pacing-induced ventricular fibrillation (PIV... more Severe hypothermia (SH, 30 °C) increases the risk of pacing-induced ventricular fibrillation (PIVF) by enhancing spatially discordant alternans (SDA). Whether moderate hypothermia (MH, 33 °C), which is clinically used for therapeutic hypothermia, also facilitates SDA remains unclear. We hypothesized that MH attenuates SDA occurrence compared with that achieved by SH, and decreases the susceptibility of PIVF. Using an optical mapping system, action potential duration (APD)/conduction velocity restitutions and thresholds of APD alternans were determined by S1 pacing in Langendorff-perfused isolated rabbit hearts. In the MH group (n = 7), S1 pacing was performed at baseline (37 °C), after 5-min MH, and after 5-min rewarming (37 °C). In the SH group (n = 9), pacing was also performed at baseline (37 °C), after 5-min SH, and after 5-min rewarming (37 °C). The thresholds of APD alternans were defined as the longest S1 pacing cycle length at which APD alternans were detected. Although the ...
This work studies nonnegative solutions for the Cauchy, Neumann, and Dirichlet problems of a logi... more This work studies nonnegative solutions for the Cauchy, Neumann, and Dirichlet problems of a logistic type reaction-diffusion equation. The finite time blowup results for nonnegative solutions under various restrictions on the coefficients of this equation are presented. Applying the results allows one to construct some reaction diffusion systems with the so-called diffusion-induced blowup phenomenon, particularly in the case of equal diffusion rates.
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
Heart Rhythm, 2015
Therapeutic hypothermia (TH) may increase the susceptibility to ventricular arrhythmias by decrea... more Therapeutic hypothermia (TH) may increase the susceptibility to ventricular arrhythmias by decreasing ventricular conduction velocity (CV) and facilitating arrhythmogenic spatially discordant alternans (SDA). 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. Langendorff-perfused isolated rabbit hearts were subjected to 30-minute moderate hypothermia (33°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°C; n = 8 for rotigaptide, n = 5 for vehicle). Using an optical mapping system, epicardial CV and SDA threshold were evaluated by S1 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. Rotigaptide increased ventricular CV during 33°C (PCL 300 ms, from 76 ± 6 cm/s to 84 ± 7 cm/s, P = .039) and 30°C (PCL 300 ms, from 62 ± 6 cm/s to 68 ± 4 cm/s, P = .008). Rotigaptide decreased action potential duration dispersion at 33°C (P = .01) and 30°C (P = .035). During 30°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°C (P = .039) and 30°C (P = .042). Rotigaptide did not change connexin43 expressions and distributions during hypothermia. 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.
Sevoflurane as a Pharmacological Probe to Explore the Genesis of the U Wave in the Electrocardiogram
ABSTRACT As one of the hypotheses, the presence of after-potentials might contribute to the genes... more ABSTRACT As one of the hypotheses, the presence of after-potentials might contribute to the genesis of U wave in ECG. Volatile anesthetics inhibit cardiac transmembrane ionic currents and intracellular calcium activity. Such pharmacological effects might explain their inhibitory actions on delayed afterdepolarizations and triggered activity. The aim of the present study was to evaluate the possible effect of sevoflurane on U wave in human beings. Perioperative ECG (lead II) were recorded and analyzed from 35 gynecologic patients (20 to 70 years old, ASA class I). All these 35 patients with sizable U waves were consecutively included in this observational study. Anesthesia was routinely induced with thiamylal, fentanyl and succinylcholine and maintained with sevoflurane and pure O 2 . U wave amplitude (U Amp) was manually measured from amplified ECG records. Discernible U wave in variable size could be identified in 35 patients (58 ± 29 µV). A negative correlation between RR interval and U Amp (r = 0.471) supported the tachycardia-augmented nature of U wave in the presence of sympathetic stimulation. U Amp was larger in extrasystolic beats (350 ± 217 % of the control, n = 11, p &lt; 0.05). Sevoflurane (1 to 1.5 MAC) significantly and reversibly suppressed U Amp (a decrease by 53 ± 27 µV, n = 35, p &lt; 0.05). The suppressive effect of sevoflurane on U Amp might suggest the role of intracellular calcium load and delayed afterdepolarizations as a possible origin of U wave in normal human beings.
Steadily Rotating Spiral Waves via the Kinematic Model
In this paper, we use the so-called kinematic model for the motions of plane curves to prove the ... more In this paper, we use the so-called kinematic model for the motions of plane curves to prove the existences of steadily rotating spiral waves and to classify them according to their angular velocities. In particular, we get two type of asymptotically Archimedian spiral waves, which are observed in many experi- ments.
Background: Volatile anesthetics inhibit cardiac transmembrane ionic currents and intracellular i... more Background: Volatile anesthetics inhibit cardiac transmembrane ionic currents and intracellular ionic activity and exert antiarrhythmic actions. Among electrocardiogram (ECG) waveforms, the effect of volatile anesthetics on U wave has never been studied. The aim of the present observational study was to evaluate the possible effect of desflurane on U wave in anesthetized patients. Methods: Peri-operative ECG tracings (lead II) were
Classification of steady solutions of the full kinematic model
Physica D: Nonlinear Phenomena, 2004
The geometric type of kinematic model governs any moving plane curve which propagates in the norm... more The geometric type of kinematic model governs any moving plane curve which propagates in the normal direction in the medium. There have appeared some results in the literature via this model. However, these results are all based upon some simplification on the model or prior phenomenological assumptions on the solutions. In this paper, we use really full kinematic model to
Over the past 15 years, molecular genetic studies have linked gene mutations to many inherited ar... more Over the past 15 years, molecular genetic studies have linked gene mutations to many inherited arrhythmogenic disorders, in particular, "ion channelopathies", in which mutations in genes encode functional units of ion channels and/or their transporter-associated proteins in patients without primary cardiac structural abnormalities. These disorders are exemplified by congenital long QT syndrome (LQTS), short QT syndrome, Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Functional and pathophysiological studies have led to better understanding of the clinical spectrum, ion channel structures and cellular electrophysiology involving dynamics of intracellular calcium cycling in many subtypes of these disorders and more importantly, development of potentially more effective pharmacological agents and even curative gene therapy. In this review, we have summarized (1) the significance of unveiling mutations in genes encoding transporter-associated proteins as the cause of congenital LQTS, (2) the technique of catheter ablation applied at the right ventricular outflow tract may be curative for severely symptomatic BrS, (3) mutations with channel function modulated by protein Kinase A-dependent phosphorylation can be the culprit of CPVT mimicry in Andersen-Tawil syndrome (LQT7), (4) ablation of the ion channel anchoring protein may prevent arrhythmogenesis in Timothy syndrome (LQT8), (5) altered intracellular Ca2+ cycling can be the basis of effective targeted pharmacotherapy in CPVT, and (6) the technology of induced pluripotent stem cells is a promising diagnostic and research tool as it has become a new paradigm for pathophysiological study of patient-and disease-specific cells aimed at screening new drugs and eventual clinical application of gene therapy. Lastly, we have discussed (7) genotype-phenotype correlation in relation to risk stratification of patients with congenital LQTS in clinical practice.
Background: Pulmonary vein (PV) sleeves, composed of cardiomyocytes, play certain roles in arrhyt... more Background: Pulmonary vein (PV) sleeves, composed of cardiomyocytes, play certain roles in arrhythmogenesis. In the literature, it has been frequently reported that PV sleeves possess intrinsic spontaneous pacemaking activity and triggered activity in normal dogs and rabbits. In contrast, other research groups presented totally opposite findings which showed absence of such pacemakers in dogs, rabbits and rats. The present study was designed to clarify this puzzle and contradiction. Methods: A novel methodology using in vitro experimentation was used to examine the electromechanical activity of whole segments of PV sleeves. The ring preparation was composed of a small piece of left atrial (LA) free wall, PV ostium and sleeve from rabbits. A circumferential contraction of the PV sleeve was measured when the preparation was electrically driven from the LA free wall. Mechanical force of the ring preparation was measured using a force transducer. The action potentials were recorded using conventional intracellular recording technique in strip preparation. Results: In 15 rabbits, no spontaneous pacemaking activity or triggered activity was found in the in vitro ring preparation of PV sleeve. The circumferential contraction of PV sleeves was external calcium-dependent. Frequency-force relation displayed a negative staircase at 0.1-0.5 Hz and a positive staircase at 1-5 Hz. Post-rest potentiation was prominent between 15 s and 120 s. Intracellular action potential recording did not display any automaticity or triggered activity in PV sleeves. Conclusion: In an intact ring preparation of rabbit PV sleeves, intrinsic spontaneous pacemaking activity or triggered activity was not found. [
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Papers by Chu-Pin Lo