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Peng-Sheng Chen

Publications and source records attributed to Peng-Sheng Chen.

At least 19 recordsLinked to original sources
PubMed2006

Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles.

BACKGROUND: The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear. METHODS AND RESULTS: We simultaneously mapped epicardial membrane potential and Ca(i) during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. Unsuccessful and type B successful defibrillation shocks were followed by heterogeneous distribution of Ca(i), including regions of low Ca(i) surrounded by elevated Ca(i) ("Ca(i) sinkholes") 31+/-12 ms after shock. The first postshock activation then originated from the Ca(i) sinkhole 53+/-14 ms after the shock. No sinkholes were present in type A successful defibrillation. A Ca(i) sinkhole also was present 39+/-32 ms after a shock on T that induced ventricular fibrillation, followed 22+/-15 ms later by propagated wave fronts that arose from the same site. This wave propagated to form a spiral wave and initiated ventricular fibrillation. Thapsigargin and ryanodine significantly decreased the upper limit of vulnerability and defibrillation threshold. We studied an additional 7 rabbits after left ventricular endocardial cryoablation, resulting in a thin layer of surviving epicardium. Ca(i) sinkholes occurred 31+/-12 ms after the shock, followed in 19+/-7 ms by first postshock activation in 63 episodes of unsuccessful defibrillation. At the Ca(i) sinkhole, the rise of Ca(i) preceded the rise of epicardial membrane potential in 5 episodes. CONCLUSIONS: There is a heterogeneous postshock distribution of Ca(i). The first postshock activation always occurs from a Ca(i) sinkhole. The Ca(i) prefluorescence at the first postshock early site suggests that reverse excitation-contraction coupling might be responsible for the initiation of postshock activations that lead to ventricular fibrillation.

Action Potentials↗
PubMed2006

Dynamic origin of spatially discordant alternans in cardiac tissue.

Alternans, a condition in which there is a beat-to-beat alternation in the electromechanical response of a periodically stimulated cardiac cell, has been linked to the genesis of life-threatening ventricular arrhythmias. Optical mapping of membrane voltage (V(m)) and intracellular calcium (Ca(i)) on the surface of animal hearts reveals complex spatial patterns of alternans. In particular, spatially discordant alternans has been observed in which regions with a large-small-large action potential duration (APD) alternate out-of-phase adjacent to regions of small-large-small APD. However, the underlying mechanisms that lead to the initiation of discordant alternans and govern its spatiotemporal properties are not well understood. Using mathematical modeling, we show that dynamic changes in the spatial distribution of discordant alternans can be used to pinpoint the underlying mechanisms. Optical mapping of V(m) and Ca(i) in paced rabbit hearts revealed that spatially discordant alternans induced by rapid pacing exhibits properties consistent with a purely dynamical mechanism as shown in theoretical studies. Our results support the viewpoint that spatially discordant alternans in the heart can be formed via a dynamical pattern formation process which does not require tissue heterogeneity.

Action Potentials↗
PubMed2006

Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition.

Aging and glycolytic inhibition (GI) are known to alter intracellular calcium ion (Ca(i)(2+)) handling in cardiac myocytes, causing early afterpotentials (EADs) and delayed afterpotentials. We hypothesized that aging and GI interact synergistically in intact hearts to generate EADs and triggered activity leading to atrial fibrillation (AF). We studied isolated and Langendorff-perfused hearts of young (age 3-5 mo, N = 8) and old (age 27-29 mo, N = 14) rats subjected to GI (0 glucose + 10 mmol/l pyruvate). Epicardial atrial activation maps were constructed using optical action potentials, while simultaneously monitoring Ca(i)(2+) by means of dual-voltage and calcium-sensitive fluorescent dyes. During GI, spontaneous AF occurred in 13 of 14 old but in no young rats. AF was initiated by EAD-induced triggered activity at the left atrial pulmonary vein junction (LA-PVJ). The triggered activity initially propagated as single wave front, but within 1 s degenerated into multiple wavelets. The EADs and triggered activity in the old atria were associated with significantly elevated diastolic Ca(i)(2+) levels at the LA-PVJ, where the time constant tau of the Ca(i)(2+) transient decline and action potential duration were significantly (P < 0.01) prolonged compared with atrial sites 5 mm away from LA-PVJ. During GI and rapid atrial pacing, spatially discordant APD and Ca(i)(2+) transient alternans developed in the old but not young atria, leading to AF. Atria in old rats had significantly more fibrotic tissue than atria in young rats. We conclude that GI interacts with the aged and fibrotic atria to amplify Ca(i)(2+) handling abnormalities that facilitate EAD-mediated triggered activity and AF.

Action Potentials↗
PubMed2006

New perspectives on the role of autonomic nervous system in the genesis of arrhythmias.

Sudden cardiac death (SCD) is a major cause of morbidity and mortality in patients with coronary artery diseases and myocardial infarction (MI). There is a circadian variation of the frequency of SCD. Beta-blocker therapy significantly reduces the incidence of SCD after MI. These clinical observations suggest a close association between ventricular arrhythmia and sympathetic activity in patients with MI. Following injury, peripheral nerves undergo Wallerian degeneration, which may be followed by neurilemma cell proliferation and axonal regeneration (nerve sprouting), resulting in sympathetic hyperinnervation. It is possible that the increased innervation after myocardial injury may result in increased sympathetic nerve density, which in turn increases the propensity for cardiac arrhythmia. While this Nerve Sprouting Hypothesis seemed to be intuitive, there was no experimental proof of a causal link between sympathetic nerve sprouting and arrhythmogenesis. We therefore performed several studies to determine the relationship between nerve sprouting and cardiac arrhythmia. We also performed direct sympathetic nerve recording in an animal model of SCD. We found that cardiac sympathetic nerves are highly plastic. In addition to MI and rapid pacing, nerve sprouting and heterogeneous sympathetic hyperinnervation may also be induced by radiofrequency ablation, hypercholesterolemia, and stem cells transplantation. The coexistence of denervated and hyperinnervated area in the diseased myocardium could result in increased electrophysiological heterogeneity during sympathetic activation, leading to ventricular arrhythmia and SCD.

Animals↗
PubMed2006

Ventricular fibrillation during no-flow global ischemia in isolated rabbit hearts.

INTRODUCTION: The dominant frequency (DF) during ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts is higher in left ventricle (LV) than in right ventricle (RV). However, the onset of VF invariably leads to global ischemia. Whether or not a high DF source exists in LV during global ischemia is unknown. METHODS AND RESULTS: By using a two-camera optical mapping system, epicardial activation patterns of VF were studied in 12 isolated rabbit hearts during baseline, no-flow global ischemia, and reperfusion. Simultaneous endocardial electrode recording was performed in 4 of the 12 hearts. Optical mapping showed type 1 VF at baseline, with multiple wandering and short-lived wavelets. After the onset of global ischemia, VF showed progressively increased spatiotemporal periodicity. The majority (65%) of VF recorded after 7 minutes of global ischemia showed type 2 VF, containing a single epicardial site with stable (> or = 3.85 seconds in duration) repetitive activities. Among the 33 sites with these activities, 24 were located near the interventricular septum, and 27 showed an epicardial breakthrough pattern with centrifugal propagation and wavebreaks distant from the focal site. After 10 minutes of global ischemia, the DF was lower on LV epicardium (5.0 +/- 1.4 Hz) than on RV epicardium (8.6 +/- 2.5 Hz, P < 0.001). However, there was no DF gradient between RV and LV endocardium (9.7 +/- 1.0 vs 9.6 +/- 0.9 Hz). CONCLUSIONS: VF during prolonged global ischemia is consistent with type 2 VF with a single subepicardial source of rapid activation, mostly near the interventricular septum. The DF in LV is not higher than in RV.

Action Potentials↗
PubMed2006

Radiofrequency catheter ablation and nerve growth factor concentration in humans.

BACKGROUND: In animal models, expression of nerve growth factor (NGF) is increased after necrotic myocardial injury. Whether radiofrequency (RF) catheter ablation increases NGF expression in humans is unclear. OBJECTIVES: The purpose of this study was to determine NGF concentrations in the aorta, coronary sinus, and peripheral veins before and after RF ablation in patients. METHODS: We sampled blood from aorta and either great cardiac vein (group 1, N = 18) or proximal (group 2, N = 20) coronary sinus before and after RF ablation. In group 3 (N = 21), peripheral venous blood was sampled before and after RF ablation and then up to postoperative day 7. In group 4 (N = 10), we sampled peripheral venous blood during diagnostic electrophysiologic study. The NGF concentration was determined by enzyme-linked immunosorbent assay. Transcardiac NGF concentration was the difference in NGF concentrations between coronary sinus and aorta. RESULTS: There was no change in transcardiac NGF concentrations in groups 1 and 2. In group 3, the NGF level did not change significantly from before the procedure (17.10 +/- 15.80 ng/mL) to immediately after the procedure (14.46 +/- 10.36 ng/mL). However, NGF levels increased significantly to 31.24 +/- 19.82 ng/mL (N = 21, P <.0001) on postoperative day 1, 26.23 +/- 16.89 ng/mL (N = 20, P <.001) on postoperative day 2, and 22.01 +/- 11.35 ng/mL (N = 16, P = .003) on postoperative day 3. NGF concentrations did not change significantly in group 4. CONCLUSION: RF ablation did not result in a detectable increase of transcardiac NGF concentration immediately after the procedure. However, the systemic NGF concentration increased significantly on postoperative days 1 to 3, suggesting that RF ablation resulted in increased NGF expression.

Atrial Fibrillation↗
PubMed2006

Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction.

OBJECTIVES: This study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction. BACKGROUND: One approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates. METHODS: We performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). RESULTS: Muscular discontinuities of widths 0.1 to 5.5 mm (1.1 +/- 1.0 mm) and abrupt 90 degrees changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes. CONCLUSIONS: Muscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures.

Adult↗
PubMed2006

From pulsus to pulseless: the saga of cardiac alternans.

Computer simulations and nonlinear dynamics have provided invaluable tools for illuminating the underlying mechanisms of cardiac arrhythmias. Here, we review how this approach has led to major insights into the mechanisms of spatially discordant alternans, a key arrhythmogenic factor predisposing the heart to re-entry and lethal arrhythmias. During spatially discordant alternans, the action potential duration (APD) alternates out of phase in different regions of the heart, markedly enhancing dispersion of refractoriness so that ectopic beats have a high probability of inducing reentry. We show how, at the cellular level, instabilities in membrane voltage (ie, steep APD restitution slope) and intracellular Ca (Cai) cycling dynamics cause APD and the Cai transient to alternate and how the characteristics of alternans are affected by different "modes" of the bidirectional coupling between voltage and Cai. We illustrate how, at the tissue level, additional factors, such as conduction velocity restitution and ectopic beats, promote spatially discordant alternans. These insights have illuminated the mechanistic basis underlying the clinical association of cardiac alternans (eg, T wave alternans) with arrhythmia risk, which may lead to novel therapeutic approaches to avert sudden cardiac death.

Animals↗
PubMed2006

Spatial distribution of nerve sprouting after myocardial infarction in mice.

BACKGROUND: Myocardial infarction (MI) elicits nerve sprouting. OBJECTIVES: The purpose of this study was to determine the spatial distribution of nerve sprouting and neurotrophic gene expression after MI. METHODS: We created MI in mice by coronary artery ligation. The hearts were removed 3 hours to 2 months after MI and examined for nerve fiber density and neurotrophic factor gene expression using Affymetrix microarray and mRNA analyses. RESULTS: The density of nerve fibers immunopositive for growth-associated protein (GAP)-43 was the highest 3 hours after MI both in the peri-infarct area and in the area remote to infarct, resulting in sympathetic (but not parasympathetic) hyperinnervation in the ventricles. The GAP-43-positive nerve fiber density of myocardium was greater in the outer transverse loop than in the inner vertical loop. The differences between these two myocardial loops peaked within 3 hours after MI and persisted for 2 months afterward. Gene expression of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-beta(3), and interleukin-1alpha was increased up to 2 months after MI compared with normal control. Expression of these growth factors was more pronounced and persistent in the peri-infarct area than in the remote area. CONCLUSION: MI induces sympathetic nerve sprouting in both peri-infarct and remote areas, more in the outer transverse loop. Selective up-regulation of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-beta(3), and interleukin-1alpha occurred in the peri-infarct area and, to a lesser extent, in the remote area.

Animals↗
PubMed2006

Circadian variations of stellate ganglion nerve activity in ambulatory dogs.

BACKGROUND: The presence of circadian variations in sympathetic outflow from the stellate ganglia is unclear. OBJECTIVES: The purpose of this study was to continuously record stellate ganglion nerve activity (SGNA) in ambulatory dogs. METHODS: We performed continuous 24-hour left (N = 3) or bilateral (N = 3) SGNA recordings in normal ambulatory dogs using implanted Data Sciences International transmitters. We also performed simultaneous ECG recording (n = 5) or simultaneous ECG and blood pressure recordings (n = 1). RESULTS: The total duration of continuous ambulatory recording averaged 41.5 +/- 16.6 days. Five dogs had persistent stable recording, and one dog developed hardware malfunction in week 3. SGNA was followed immediately (<1 second) by heart rate and blood pressure elevation and a reduced standard deviation of consecutive activation cycle length (SDNN) from 236 +/- 93 ms to 121 +/- 51 ms (P = 0.007). Heart rate correlated significantly with SGNA. When there was a sudden increase of SGNA, the sudden increase occurred bilaterally in 90% of the episodes. Both heart rate and SGNA showed statistically significant (P <.01) circadian variation. Nadolol (20 mg/day for 5 days) reduced average heart rate from 99 +/- 8 bpm at baseline to 88 +/- 9 bpm (N = 6, P = .001) but did not significantly alter SGNA. Immunohistochemical staining of the stellate ganglia showed tyrosine hydroxylase-positive ganglion cells and nerves at the recording site. CONCLUSION: There is a circadian variation in sympathetic outflow from canine stellate ganglia. Circadian variation of SGNA is an important cause of circadian variations of cardiac sympathetic tone.

Adrenergic beta-Antagonists↗
PubMed2006

Dyslipidemia is associated with ventricular tachyarrhythmia in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Ventricular tachyarrhythmia developing in the acute stage of myocardial infarction (MI) is an important cause of sudden cardiac death. The aim of this study was to determine whether dyslipidemia is associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) during the acute stage of ST-segment elevation MI (STEMI). METHODS: A total of 58 patients experiencing VT/VF within 24 hours after the onset of MI were selected as the study group. A group of 58 patients with MI but without VT/VF was selected as the control group matched for sex (overall, 104 males), age (overall, 58 +/- 10 years), and the use of thrombolytic therapy (n = 82). The lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride were measured during the first week and at the third month after the index MI. Other coronary risk factors, and clinical, hemodynamic and angiographic characteristics were also included in the assessment. RESULTS: During the acute stage, patients with VT/VF had higher levels of LDL-C and lower blood pressure on initial arrival at our hospital. At the 3-month follow-up, those patients with VT/VF showed higher levels of TC, LDL-C and triglyceride. Multivariate analysis revealed that LDL-C (p < 0.001) at the 3-month follow-up, mean blood pressure on arrival (p < 0.01), and the difference in triglyceride levels between the first week and the third month (p < 0.05) were independent predictors for the occurrence of VT/VF in the acute stage of MI. CONCLUSION: This study suggests that dyslipidemia imposes a higher risk of developing tachyarrhythmia in the acute phase of STEMI.

Aged↗
PubMed2006

Role of the posterior papillary muscle and purkinje potentials in the mechanism of ventricular fibrillation in open chest dogs and Swine: effects of catheter ablation.

BACKGROUND: Papillary muscle (PM) ablation may terminate ventricular fibrillation (VF) in rabbit hearts. Whether or not PM ablation prevents ventricular fibrillation (VF) induction in large animals is unknown. METHODS: We performed noncontact endocardial mapping and/or high-density epicardial mapping during VF in 12 dogs and 16 swine and tested the effects of posterior PM (PPM) ablation on VF inducibility. RESULTS: During VF in progressive global ischemia (3 swine and 2 dogs), the highest dominant frequency (DF) was near PPM. The majority of the reentrant wavefronts during a propranolol infusion (swine) were anchored to the PPM. Purkinje potentials onset were recorded on the PPM both during sinus rhythm and during VF. Radiofrequency (RF) ablation of the endocardium on the PPM with a linear extension of the ablation line from the PPM to the mitral valve annulus and then the left ventricular apex in 7 dogs reduced the VF inducibility from 100% at baseline to 22% after ablation (P < 0.0001). RF applications to the anterolateral wall of dogs (n = 3) did not prevent VF induction. The application of RF energy near the PPM frequently initiated VF in swine (n = 7), preventing subsequent testing of VF inducibility. CONCLUSION: In dogs and swine, the highest DF and majority of reentrant wavefronts during VF with acute global ischemia or during a propranolol infusion were located on the PPM. RF ablation targeted at the PPM reduced the inducibility of VF in normal dogs. However, the same ablation provoked incessant VF in swine, preventing subsequent testing of VF inducibility.

Animals↗
PubMed2006

Vein of Marshall activity during sustained atrial fibrillation.

BACKGROUND: The human vein of Marshall (VOM) activation patterns during sustained (persistent or permanent) atrial fibrillation (AF) have not been studied in detail. METHODS: VOM was cannulated via coronary sinus in six patients (67.3 +/- 7.5 years old) having either persistent (N = 4) or permanent (N = 2) AF presenting for radiofrequency catheter ablation. RESULTS: At sinus rhythm in patients with persistent AF, there were frequent ectopic beats from the VOM as well as from left and right pulmonary veins (PVs). The ectopic activity originating from the VOM was highly fragmented. The P wave morphology associated with VOM ectopy was isoelectric in leads I and aVL, positive in leads II, III, aVF, and V2-V5, which is similar to the P wave morphology associated with left PV ectopic beats. During AF the activation cycle length at VOM was 140 +/- 31 msec, which was significantly shorter than that in other atrial sites (P < 0.05). Similarly, the dominant frequency at VOM (9.71 Hz +/- 1.52 Hz) was significantly higher than that at other atrial sites (P < 0.0001). In one patient, VOM ablation was associated with AF termination during radiofrequency energy application. CONCLUSIONS: Ectopic activity with complex local electrogram originating from VOM is commonly seen in patients with sustained AF. The P wave morphology associated with the ectopic beats from VOM and from the left PVs was similar. The rate of activation at VOM is significantly faster than other atrial and PV sites during AF. These findings show that rapid activation is present in the VOM during sustained AF in human patients.

Aged↗
PubMed2006

The mechanisms of atrial fibrillation.

In this article we have reviewed the mechanisms of atrial fibrillation (AF) with special emphasis on the thoracic veins. Based on a number of features, the thoracic veins are highly arrhythmogenic. The pulmonary vein (PV)-left atrial (LA) junction has discontinuous myocardial fibers separated by fibrotic tissues. The PV muscle sleeve is highly anisotropic. The vein of Marshall (VOM) in humans has multiple small muscle bundles separated by fibrosis and fat. Insulated muscle fibers can promote reentrant excitation, automaticity, and triggered activity. The PV muscle sleeves contain periodic acid-Schiff (PAS)-positive large pale cells that are morphologically reminiscent of Purkinje cells. These special cells could be the sources of focal discharge. Antiarrhythmic drugs have significant effects on PV muscle sleeves both at baseline and during AF. Both class I and III drugs have effects on wavefront traveling from PV to LA and from LA to PV. Separating the thoracic veins and the LA with ablation techniques also prevents PV-LA interaction. By reducing PV-LA interaction, pharmacological therapy and PV isolation reduce the activation rate in PV, intracellular calcium accumulation, and triggered activity. Therefore, thoracic vein isolation is an important technique in AF control. We conclude that thoracic veins are important in the generation and maintenance of AF.

Aging↗
PubMed2005

Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties.

UNLABELLED: Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n=7] had significantly higher LVEF than controls [n=8] (49+/-2% vs. 44+/-3%, P=0.015) and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P<or=0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. CONCLUSION: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

Animals↗