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Biomedical subjects

Peng-Sheng Chen

Publications and source records attributed to Peng-Sheng Chen.

At least 55 records · Page 3Linked to original sources
PubMed2004

Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs.

Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial infarction (MI) both contribute to arrhythmogenesis and sudden death. However, the mechanisms responsible for nerve sprouting after MI are unclear. The expression of nerve growth factor (NGF), growth associated protein 43 (GAP43), and other nerve markers were studied at the infarcted site, the noninfarcted left ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time points (30 minutes to 1 month) after MI. Transcardiac (difference between coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the immediate elevation of the transcardiac NGF concentration within 3.5 hours after MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was earlier and more pronounced at the infarcted site than the noninfarcted LVFW. However, cardiac nerve sprouting and sympathetic hyperinnervation were more pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week after MI. The NGF and GAP43 protein levels significantly increased in the LSG from 3 days (P<0.01 for all) after MI, without a concomitant increase in mRNA. There was persistent elevation of NGF levels in aorta and coronary sinus within 1 month after MI. We conclude MI results in immediate local NGF release, followed by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43 are transported retrogradely to LSG, which triggers nerve sprouting at the noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43 expression at the infarcted site underlies the mechanisms of cardiac nerve sprouting after MI.

Animals↗
PubMed2004

Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death.

OBJECTIVES: We sought to develop a high-yield canine model of sudden cardiac death (SCD). BACKGROUND: Because electrical stimulation is a powerful means to elicit nerve sprouting, we hypothesize that subthreshold electrical stimulation is more effective than nerve growth factor (NGF) infusion in inducing nerve sprouting and SCD in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). METHODS: We gave subthreshold electrical stimulation to the left stellate ganglion (LSG) in six normal dogs for 41 +/- 9 days (protocol 1) and to six dogs with MI and CAVB for 41 +/- 29 days, while continuously monitoring their cardiac rhythm (protocol 2). We also monitored the rhythm of two dogs with MI, CAVB, and NGF infusion to the LSG and determined the ventricular nerve density in six healthy control dogs. RESULTS: In protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p < 0.01). In protocol 2, there was a high magnitude of cardiac nerve sprouting in all dogs studied. Ventricular tachycardia > or =8 beats and > or =20 beats was more frequent in dogs with electrical stimulation than in dogs with NGF infusion to the LSG (36 +/- 60 and 11 +/- 17 vs. 4.7 +/- 6.1 and 0.1 +/- 0.33 episodes per day, p < 0.05 and p < 0.03, respectively). Four of six dogs in protocol 2 had SCD. CONCLUSIONS: Subthreshold electrical stimulation of the LSG induces cardiac nerve sprouting and sympathetic hyperinnervation and facilitates the development of a high-yield canine model of ventricular arrhythmia and SCD.

Animals↗
PubMed2004

Thoracic vein ablation terminates chronic atrial fibrillation in dogs.

The thoracic vein hypothesis of chronic atrial fibrillation (AF) posits that rapid, repetitive activations from muscle sleeves within thoracic veins underlie the mechanism of sustained AF. If this is so, thoracic vein ablation should terminate sustained AF and prevent its reinduction. Six female mongrel dogs underwent chronic pulmonary vein (PV) pacing at 20 Hz to induce sustained (>48 h) AF. Bipolar electrodes were used to record from the atria and thoracic veins, including the vein of Marshall, four PVs, and the superior vena cava. Radio frequency (RF) application was applied around the PVs and superior vena cava and along the vein of Marshall until electrical activity was eliminated. Computerized mapping (1,792 electrodes, 1 mm resolution) was also performed. Sustained AF was induced in 30.6 +/- 6.5 days, and ablation was done 17.3 +/- 8.5 days afterward. Before ablation, the PVs had shorter activation cycle lengths than the atria, and rapid, repetitive activations were observed in the PVs. All dogs converted to sinus rhythm during (n = 4 dogs) or within 90 min of completion of RF ablation. Rapid atrial pacing afterward induced only nonsustained (<60 s) AF in all dogs. Average AF cycle lengths after reinduction were significantly (P = 0.01) longer (183 +/- 31.5 ms) than baseline (106 +/- 16.2 ms). There were no activation cycle length gradients after RF application. We conclude that thoracic vein ablation converts canine sustained AF into sinus rhythm and prevents the reinduction of sustained AF. These findings suggest that thoracic veins are important in the maintenance of AF in dogs.

Animals↗
PubMed2004

Intracellular Ca dynamics in ventricular fibrillation.

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Cai transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/- 0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001). Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13) compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001). Spatially, Cai waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Cai is closely associated with Vm closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Cai release events occur and may influence wavebreak by altering Vm and APD locally.

Animals↗
PubMed2004

Sympathetic nerve sprouting after orthotopic heart transplantation.

BACKGROUND: Although many studies have documented sympathetic re-innervation in transplanted hearts (allografts) using chemical, imaging, and electrophysiologic methods, little histopathologic proof of this process exists. METHODS AND RESULTS: We used immunohistochemical techniques with antibodies to S-100 protein, to growth-associated protein 43 (GAP43), and to tyrosine hydroxylase (TH) to detect nerves in the left ventricles in allografts from 29 consecutive recipients. Reasons for transplantation included ischemic heart disease (IHD, n=16), non-ischemic dilated cardiomyopathy (DCM, n=12), and both (n=1). We assessed nerve densities (nerves/mm2) with respect to time after transplantation in the endocardium; in the mid-myocardium; and around intramyocardial blood vessels, scars, foci of rejection, and Quilty lesions. Six normal hearts were used for comparison. As in normal hearts, all 29 allografts had epicardial nerve trunks that extended into the mid-myocardium around blood vessels. Although the total number of nerves (S100-positive) progressively decreased over time, GAP43-positive nerves around the blood vessels increased with time (p <0.005). We also observed abundant TH-positive nerves. The density of S100-positive nerves around blood vessels was greater in those undergoing transplantation for IHD (113 +/- 88) than in those with prior DCM (54 +/- 49, p <0.05). Nerve density in each area varied greatly. CONCLUSIONS: Heterogeneous sympathetic nerve sprouting and re-innervation occurred around blood vessels in the allografts. The magnitude of nerve sprouting increased with time and varied greatly from patient to patient. Patients with IHD had greater nerve sprouting and re-innervation than did those with DCM.

Adult↗
PubMed2004

Nerve sprouting induced by radiofrequency catheter ablation in dogs.

OBJECTIVES: The purpose of this study was to test the hypothesis that radiofrequency (RF) catheter ablation results in cardiac nerve sprouting. BACKGROUND: Nerve sprouting plays a role in cardiac arrhythmogenesis. Whether or not nerve sprouting occurs after RF catheter ablation is unclear. METHODS: We performed RF catheter ablation in the right atrium (RA) and right ventricle (RV) in 10 dogs, which then were sacrificed in 2 hours (acute group, n = 5) or 1 month (chronic group, n = 5). Seven normal dogs were used as control. Immunohistochemical staining for growth-associated protein 43 (GAP-43) was performed to measure growing (sprouting) nerves. RESULTS: A significant increase of GAP-43 immunoreactive nerve fiber density was observed at the RA ablation sites in 2 hours (4,410 +/- 1,379 microm(2)/mm(2)) and in 1 month (2,948 +/- 666 microm(2)/mm(2)) after ablation compared to controls (1,377 +/- 471 microm(2)/mm(2), P = .0001). At remote sites (>2 cm away from ablation sites) of RA, RF ablation also resulted in robust nerve sprouting in both the acute group (5,846 +/- 3241 microm(2)/mm(2)) and the chronic group (6,030 +/- 2226 microm(2)/mm(2)). RF ablation in the RV did not increase nerve density at the ablation sites, but nerve density was increased at remote sites in 2 hours (1,345 +/- 451 microm(2)/mm(2), P = .0136) that was reduced down to the normal control level (722 +/- 337 microm(2)/mm(2)) in 1 month. CONCLUSIONS: Nerve sprouting occurred within 2 hours after RF ablation in both the RA and RV and persisted for at least 1 month in the RA but not the RV. The increased GAP-43(+) nerve densities developed at both the ablation and the remote sites.

Animals↗
PubMed2004

Electrophysiological characterization of cardiac veins in humans.

BACKGROUND: The coronary sinus is a complex structure with a surrounding myocardial coat and muscle bundles that course within it. The purpose of this study was to evaluate the electrical activity of the coronary sinus (CS), great cardiac vein (GCV) and related structures, such as the Vein of Marshall (VOM). METHODS AND RESULTS: Data obtained from adult ( n = 114) and pediatric patients ( n = 16) were analyzed. The width of atrial electrograms (EGMs) within the CS at a basic pacing cycle length of 600 ms was 46 +/- 7.4 ms (mean +/- SD) vs. 29.7 +/- 6.3 ms in the GCV ( p < 0.01). With decremental pacing the width of the EGM within the CS at 300 ms increased to 66.6 +/- 8.5 ms ( p < 0.1 compared to CS EGM at pacing cycle length of 600 ms). The width of the EGM within the GCV increased from 29.7 +/- 6.3 ms at a pacing cycle length of 600 ms to 34.6 +/- 6.0 at 300 ms ( p = NS). There were no significant differences in the atrial EGM width between CS and GCV in the pediatric patients. CONCLUSIONS: We conclude that atrial electrograms are wider in the CS but not in the GCV. This finding can be explained by the presence of a myocardial coat around the CS. The rate response characteristics of the atrial electrograms within the CS are consistent with a lack of tight coupling between muscle bundles and the CS musculature. Further, the absence of such differences in pediatric patients could partly explain relative differences in types of supraventricular arrhythmias seen in different age groups.

Adolescent↗
PubMed2004

Low-affinity nerve growth factor receptor p75NTR immunoreactivity in the myocardium with sympathetic hyperinnervation.

INTRODUCTION: We previously demonstrated the relationship between sympathetic nerve density in myocardium and the occurrences of ventricular arrhythmia. Nerve growth factor (NGF) regulates myocardial sympathetic innervation. However, it is unclear whether the NGF high-affinity receptor tyrosine kinase A (TrkA) and the NGF low-affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart. The aim of this study was to determine the density and location of TrkA and p75NTR in canine ventricles with sympathetic hyperinnervation. METHODS AND RESULTS: Myocardial sympathetic hyperinnervation was induced by local infusion of NGF into myocardium or left stellate ganglia, or chronic subthreshold electric stimulation to the left stellate ganglia. The results showed that TrkA immunoreactivity was absent in the myocardium. Low-affinity receptor p75NTR immunoreactivity was present in axons, Schwann cells, and interstitial cells of sympathetic nerves, as well as in interstitial cells of the myocardium. The density of p75NTR immunolabeled myocardial interstitial cells at the NGF infusion site was lower than that at the site remote from NGF infusion, yet the sympathetic nerve density was higher at the infusion site than the remote area. The density of p75NTR also was lower in the myocardium with high sympathetic nerve density, induced by NGF infusion or chronic electric stimulation of the left stellate ganglia, compared to control groups. CONCLUSION: The data indicate that p75NTR may be the main NGF receptor in the myocardium, and p75NTR immunopositive interstitial cells may have a role in regulating sympathetic nerve growth in canine heart.

Animals↗
PubMed2004

Improvement of defibrillation efficacy with preshock synchronized pacing.

INTRODUCTION: We previously demonstrated that wavefront synchronization by spatiotemporal excitable gap pacing (Sync P) is effective at facilitating spontaneous termination of ventricular fibrillation (VF). Therefore, we hypothesized that a spatiotemporally controlled defibrillation (STCD) strategy using defibrillation shocks preceded by Sync P can improve defibrillation efficacy. METHOD AND RESULTS: We explored the STCD effects in 13 isolated rabbit hearts. During VF, a low-voltage gradient (LVG) area was synchronized by Sync P for 0.92 second. For Sync P, optical action potentials (OAPs) adjacent to four pacing electrodes (10 mm apart) were monitored. When one of the electrodes was in the excitable gap, a 5-mA current was administered from all electrodes. A shock was delivered 23 ms after the excitable gap when the LVG area was unexcitable. The effects of STCD was compared to random shocks (C) by evaluating the defibrillation threshold 50% (DFT(50); n = 35 for each) and preshock coupling intervals (n = 208 for STCD, n = 172 for C). Results were as follows. (1) Sync P caused wavefront synchronization as indicated by a decreased number of phase singularity points (P < 0.0001) and reduced spatial dispersion of VF cycle length (P < 0.01). (2) STCD decreased DFT(50) by 10.3% (P < 0.05). (3) The successful shocks showed shorter preshock coupling intervals (CI; P < 0.05) and a higher proportion of unexcitable shock at the LVG area (P < 0.001) than failed shocks. STCD showed shorter CIs (P < 0.05) and a higher unexcitable shock rate at LVG area (P < 0.05) than C. CONCLUSION: STCD improves defibrillation efficacy by synchronizing VF activations and increasing probability of shock delivery to the unexcitable LVG area.

Animals↗
PubMed2004

Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle.

INTRODUCTION: We previously reported that a normal ventricle can demonstrate two types of ventricular fibrillation (VF), depending on the underlying electrophysiologic characteristics at the time of VF induction. We hypothesize that the two types of VF can coexist in acutely ischemic ventricles. METHODS AND RESULTS: Optical mapping studies were performed with di-4ANEPPS in 15 Langendorff-perfused rabbit hearts. Coronary artery branches were ligated to create regional ischemia in 10 hearts. Action potential duration measured to 50% repolarization (APD50) during ischemia showed an area with uniformly shortened APD50 (zone 1), an area with normal or lengthened APD50 (zone 3), and an area in between with an APD50 gradient (zone 2). Ischemia flattened APD restitution (APDR) slope and reduced conduction velocity in zone 1, creating a condition for type II VF. APDR steepened and the conduction velocity changed little in the nonischemic zone (zone 3), creating a condition for type I VF. During induced VF, the dominant frequency in zones 2 and 3 progressively increased after ischemia onset. The dominant frequency in zone 1 (ischemic zone) first decreased and then slightly increased but typically remained less than the dominant frequency in zone 3. The number of wavebreaks increased with time in all three zones (baseline: 4.3 +/- 1.5; 30 min: 11.7 +/- 5.6; 60 min: 15.6 +/- 11 per frame; P < 0.01). CONCLUSION: Two types of VF can coexist during acute regional ischemia. Both ischemic and nonischemic regions develop proarrhythmic changes during regional ischemia, thus contributing to increased ventricular vulnerability to VF and sudden death during acute coronary occlusion.

Analysis of Variance↗
PubMed2004

Effects of procainamide on electrical activity in thoracic veins and atria in canine model of sustained atrial fibrillation.

Focal discharges (FDs) are present in thoracic veins during atrial fibrillation (AF). We hypothesize that procainamide exerts its anti-AF action by suppressing FDs in the thoracic veins. We studied six mongrel dogs (22-27 kg) with sustained (>6 h) AF induced by 47 +/- 20 days of chronic rapid LA appendage (LAA) or pulmonary vein (PV) pacing. Procainamide was infused intravenously until AF was terminated or a cumulative dose of 20 mg/kg was reached. High-resolution mapping during AF showed FDs in the vein of Marshall, PVs, and the LAA. Procainamide significantly (P < 0.05) reduced the frequency of these FDs and suppressed the interactions of wave fronts between PVs and LA. The cumulative dose of PA needed to terminate AF correlated negatively (r =-0.9, P < 0.05) with the baseline effective refractory period (ERP) of PV and positively (r = 0.8, P < 0.05) with the baseline maximum dominant frequency (DF) of AF. In four of five dogs, AF converted to atrial tachycardia originating from the PVs before termination. Attempts to reinduce sustained AF were unsuccessful in these five dogs. AF was resistant to procainamide in the sixth dog. In conclusion, procainamide reduced the rate of FDs in the thoracic veins and the LA and suppressed the interaction between PVs and LA. Second, FDs in the PV are more resistant to procainamide's action than FDs in the atria. Third, inherent PV ERP is important in determining the antifibrillatory efficacy of procainamide.

Animals↗
PubMed2004

Ventricular fibrillation: new insights into mechanisms.

Device therapy with implantable cardioverter-defibrillators is currently the only proven effective therapy against sudden cardiac death due to ventricular fibrillation. However, the expanded clinical indications for device therapy come at a staggering cost to an already overburdened health care system. Given these statistics, it is both highly desirable and economically imperative to develop alternative therapies. New insights into the mechanisms of ventricular fibrillation, particularly the role of dynamic factors causing wave instability, are providing a promising avenue for developing novel therapies to prevent sudden cardiac death.

Action Potentials↗
PubMed2003

Catheter ablation of ventricular fibrillation in rabbit ventricles treated with beta-blockers.

BACKGROUND: A therapeutic implication of the focal-source hypothesis of ventricular fibrillation (VF) is that VF can be terminated by focal ablation. We hypothesize that beta-adrenergic receptor blockade converts multiple-wavelet VF to focal-source VF and that this focal source is located near the papillary muscle (PM). METHODS AND RESULTS: We used optical mapping techniques to study the effects of propranolol (0.3 mg/L) on VF dynamics in Langendorff-perfused rabbit hearts. The left ventricular (LV) anterior wall was mapped and optical action potential duration restitution (APDR) was determined at 25 epicardial sites. We performed ablation during VF of the left anterior PM in hearts with (N=6) or without (N=6) cytochalasin infusion, the LV lateral epicardium (Epi group, N=3), and the LV endocardium (Endo group, N=3). The PM was also ablated in 3 hearts without propranolol (control group). Propranolol converted multiple-wavelet VF to slow VF with reentry localized to the PM. Propranolol decreased the maximal slope of the APDR curve (P<0.001) as well as its spatial heterogeneity (P<0.01) and conduction velocity (P=0.01) while increasing the VF cycle length (P<0.001). PM ablation terminated VF during propropranolol infusion with (6 of 6, 100%) or without (4 of 6, 67%) cytochalasin D and significantly reduced inducibility. VF did not terminate in the Epi, Endo, and control groups (P<0.001). CONCLUSIONS: Propranolol flattens the APDR curve and reduces conduction velocity, converting multiple-wavelet VF into VF with a focal source anchored to the PM. Ablation of this focal source may terminate VF.

Action Potentials↗