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Peng-sheng Chen - One of the best experts on this subject based on the ideXlab platform.
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Nerve Sprouting and Cardiac Arrhythmias
Cardiac Electrophysiology, 2013Co-Authors: Lan S. Chen, Peng-sheng ChenAbstract:After division, crushing, interference of blood supply, or other means of injury, the peripheral Nerves undergo Wallerian degeneration and axonal regeneration. This regenerative process, termed Nerve Sprouting , is well described, both in the central nervous system and in the peripheral nervous system. If the Nerve sprouts form synapses, they may result in permanent changes of local innervation, leading to functional consequences. Myocardial infarction (MI) causes Nerve injury and regional sympathetic denervation. Afterward, Nerve Sprouting occurs and results in a regional increase of sympathetic hyperinnervation. 1 Although the magnitude of Nerve Sprouting varies from subject to subject, there is a correlation between the density of sympathetic Nerve and occurrence of ventricular arrhythmia. 2 3 In this chapter, we will review the relationship between sympathetic Nerve Sprouting and cardiac arrhythmia.
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Nerve Sprouting defibrillation and calcium waves
2013Co-Authors: Mitsunori Maruyama, Lan S. Chen, Shengmei Zhou, Gyoseung Hwang, Su Kiat Chua, Po Cheng Chang, Tomohiko Ai, Peng-sheng ChenAbstract:Zoll et al. first reported the successful termination of ventricular fibrillation (VF) by externally applied electrical countershocks. In the same seminal report, the authors also discovered that recurrent VF may occur shortly after successful ventricular defibrillation. Due to the general availability of the implantable cardioverter-defibrillator (ICD), patients may survive the initial VF episodes but suffer from multiple recurrent VF and defibrillation shocks within a short period of time. The clustering of recurrent VF episodes (electrical storm) after initial successful defibrillation suggests that the first episode of VF begets subsequent episodes of VF. The mechanisms by which VF begets VF remains poorly understood. In this chapter we will discuss the mechanisms of neural remodeling after myocardial infarction (MI). We propose that Nerve Sprouting and sympathetic hyperinnervation occur after MI. The increased sympathetic Nerve densities in the heart is highly heterogeneous, with portions of the heart showing increased Nerve densities while the remaining portions of the heart showing denervation. During sympathetic Nerve activation, there is increased heart rate and augmented intracellular calcium (Cai) concentration. In addition, we found that the action potential duration (APD) is abbreviated after a fibrillation-defibrillation episode in failing ventricles. The shortened APD and the elevated Cai promotes late phase 3 early afterdepolarization (EAD) and Ca2+-transient triggered firing (CTTF), leading to recurrent cardiac fibrillation. We also propose that the mechanisms of APD shortening after fibrillation-defibrillation episodes in the failing (but not in the normal) ventricles are due to the upregulation of small conductance Ca2+ activated potassium (SK) currents. We hope that these discussions will help the readers better understand the relevance of cardiac neural remodeling and electrical remodeling in the mechanisms of arrhythmogenesis.
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Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.
Cardiovascular Pathology, 2011Co-Authors: Bich Lien Nguyen, Michael C Fishbein, Peng-sheng Chen, Hongmei Li, Carlo Gaudio, Lan S. ChenAbstract:Abstract Introduction Myocardial infarction (MI) results in cardiac Nerve Sprouting in the myocardium. Whether or not similar neural remodeling occurs in the stellate ganglia (SGs) is unknown. We aimed to test the hypothesis that MI induces bilateral SG Nerve Sprouting. Methods Acute MI was created by coronary artery ligation in rabbits (n=12). Serum Nerve growth factor (NGF) level was measured by enzyme-linked immunosorbent assay. The hearts and bilateral SGs were harvested for immunohistochemistry after 1 week in six rabbits and after 1 month in six rabbits. Immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), choline acetyltransferase (ChAT), and synaptophysin (SYN) was performed to determine the magnitude of Nerve Sprouting. Tissues from six normal rabbits were used as controls. Nerve density was determined by computerized morphometry. Results Myocardial infarction results in increased serum NGF levels at 1 week (1519.8±632.2 ng/ml) that persist up to 1 month (1361.2±176.3 ng/ml) as compared to controls (89.6±34.9 ng/ml) (P=.0002 and P=.0001, respectively). Immunostaining demonstrated Nerve Sprouting and hyperinnervation in both SGs after MI. The Nerve densities (μm2/ganglion cell) in SG 1 week after MI and 1 month after MI and those in control groups, respectively, were as follows: GAP43: 278±96, 225±39, and 149±57 (P=.01); SYN: 244±152, 268±115, and 102±60 (P=.02); TH: 233±71, 180±50, and 135±68 (P=.047); ChAT: 244±100, 208±46, and 130±41 μm2/cell (P=.01). Conclusions Myocardial infarction increases serum NGF levels and induces Nerve Sprouting and hyperinnervation in bilateral SGs for at least 1 month after MI. The hyperinnervation includes both adrenergic axons and cholinergic axons in the SG.
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ifats collection human adipose tissue derived stem cells induce angiogenesis and Nerve Sprouting following myocardial infarction in conjunction with potent preservation of cardiac function
Stem Cells, 2009Co-Authors: Brian H Johnstone, Michael C Fishbein, Peng-sheng Chen, Todd G Cook, Keith L MarchAbstract:The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and Nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac Nerve Sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors.
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atrial sympathetic and parasympathetic Nerve Sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs
Cardiovascular Pathology, 2008Co-Authors: Moshe Swissa, Michael C Fishbein, Shengmei Zhou, Peng-sheng Chen, Lan S. ChenAbstract:Abstract Background Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce Nerve Sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria. Methods and Results We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41±9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic Nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of Nerve structures immunopositive to the SYN, GAP43, TH, and ChAT ( P P Conclusions Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.
Michael C Fishbein - One of the best experts on this subject based on the ideXlab platform.
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Subcutaneous Nerve Stimulation Reduces Sympathetic Nerve Activity in Ambulatory Dogs with Myocardial Infarction
Heart Rhythm, 2020Co-Authors: Yuan Yuan, Michael C Fishbein, Ye Zhao, Johnson Wong, Wei-chung Tsai, Zhaolei Jiang, Ryan A. Kabir, Changyu Shen, Lan S. ChenAbstract:Background Subcutaneous Nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion Nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through Nerve Sprouting. Objective The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. Methods In the experimental group, a radio transmitter was implanted during the first sterile surgery to record Nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. Results In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 μV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 μV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 μV (P Conclusion ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac Nerve Sprouting after acute MI.
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Antiarrhythmic and proarrhythmic effects of subcutaneous Nerve stimulation in ambulatory dogs.
Heart Rhythm, 2019Co-Authors: Mu Chen, Michael C Fishbein, Yuan Yuan, Johnson Wong, Changyu Shen, Zhuo Wang, Zhenhui Chen, Maria B. Grant, Thomas H. EverettAbstract:Background High output subcutaneous Nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac Nerve Sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.25 mA (n = 4), 1.5 mA (n = 4), 2.5 mA (n = 4), and 3.5 mA (n = 4). Results As compared with baseline, the changes in the durations of PAT episodes per 48 hours were significantly different among different groups (sham, −5.0 ± 9.5 seconds; 0.25 mA, 95.5 ± 71.0 seconds; 1.5 mA, −99.3 ± 39.6 seconds; 2.5 mA, −155.3 ± 87.8 seconds; and 3.5 mA, −76.3 ± 44.8 seconds; P Conclusion In ambulatory dogs, low output ScNS causes cardiac Nerve Sprouting and increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.
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Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias
Autonomic Neuroscience: Basic and Clinical, 2013Co-Authors: Olujimi A. Ajijola, Michael C Fishbein, Jonathan J. Wisco, H. Wayne Lambert, Aman Mahajan, Elena Stark, Kalyanam ShivkumarAbstract:5.1 Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias O.A. Ajijola, J.J. Wisco, H.W. Lambert, E.M. Stark, A. Mahajan, M.C. FIshbein, K. Shivkumar (University of California, Los Angeles, CA, USA), (West Virginia University, Morgantown, WV, USA) Background: Intra-myocardial Nerve Sprouting after myocardial infarction is associated with ventricular arrhythmias (VAs). Whether human stellate ganglia remodel in association with cardiac pathology was unknown. The purpose of our study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. Methods and Results: Left stellate ganglia (LSG) were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias, and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed extensively. We classified ganglia from normal; scarred; and non-ischemic cardiomyopathic hearts without scar as NL (n = 3); SCAR (n = 24); and NICM (n = 7), respectively. Within LSG, we measured neuronal size, density, fibrosis, synaptic density and Nerve Sprouting. Nerve density and Sprouting were also quantified in obtained cadaveric hearts. Mean neuronal size in NL, SCAR, and NICM groups were; 320 ± 4 μm, 372 ± 10 μm, and 435± 10 μm (p= 0.002). No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in SCAR and NICM ganglia were 57.8 ± 11.2um/mm (p= 0.039) and 44.5 ± 7.9um/mm (p= 0.084) respectively, compared to the NL, 17.8 ± 7um/mm (overall p = 0.162). There were no significant differences in LSG Nerve Sprouting ormyocardial Nerve density between the groups. In a porcinemodel of chronic infarcts, neurochemical changes were also observed in addition to increased neuronal size. Conclusions: Neuronal hypertrophy within LSG is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial Nerve Sprouting and Nerve density were not significantly different. A porcine model recapitulates these findings, and demonstrates neurochemical rmodeling. These changes may be related to increased cardiac sympathetic signaling and VAs. Further studies are needed to determine the electrophysiologic consequences of extra-cardiac neuronal remodeling in humans. doi:10.1016/j.autneu.2013.05.030
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Extracardiac Neural Remodeling in Humans With Cardiomyopathy
Circulation-arrhythmia and Electrophysiology, 2012Co-Authors: Olujimi A. Ajijola, Michael C Fishbein, Jonathan J. Wisco, H. Wayne Lambert, Aman Mahajan, Elena Stark, Kalyanam ShivkumarAbstract:Background— Intramyocardial Nerve Sprouting after myocardial infarction is associated with ventricular arrhythmias. Whether human stellate ganglia remodel in association with cardiac pathology is unknown. The purpose of this study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. Methods and Results— Left stellate ganglia were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed. We classified ganglia from normal, scarred, and nonischemic cardiomyopathic hearts without scar as NL (n=3), SCAR (n=24), and NICM (n=7), respectively. Within left stellate ganglia, neuronal size, density, fibrosis, synaptic density, and Nerve Sprouting were determined. Nerve density and Sprouting were also quantified in cadaveric hearts. Mean neuronal size in normal, scarred, and nonischemic cardiomyopathic hearts without scar groups were 320±4 μm2, 372±10 μm2, and 435±10 μm2 ( P =0.002), respectively. No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in ganglia from SCAR and NICM groups were 57.8±11.2 μm2/mm2 ( P =0.084) and 44.5±7.9 μm2/mm2 ( P =0.039), respectively, compared with the normal group, 17.8±7 μm2/mm2 (overall P =0.162). There were no significant differences in left stellate ganglia Nerve Sprouting or myocardial Nerve density between the groups. Conclusions— Neuronal hypertrophy within left stellate ganglia is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial Nerve Sprouting and Nerve density were not significantly different. These changes may be related to increased cardiac sympathetic signaling and ventricular arrhythmias. Further studies are needed to determine the electrophysiological consequences of extracardiac neuronal remodeling in humans.
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Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.
Cardiovascular Pathology, 2011Co-Authors: Bich Lien Nguyen, Michael C Fishbein, Peng-sheng Chen, Hongmei Li, Carlo Gaudio, Lan S. ChenAbstract:Abstract Introduction Myocardial infarction (MI) results in cardiac Nerve Sprouting in the myocardium. Whether or not similar neural remodeling occurs in the stellate ganglia (SGs) is unknown. We aimed to test the hypothesis that MI induces bilateral SG Nerve Sprouting. Methods Acute MI was created by coronary artery ligation in rabbits (n=12). Serum Nerve growth factor (NGF) level was measured by enzyme-linked immunosorbent assay. The hearts and bilateral SGs were harvested for immunohistochemistry after 1 week in six rabbits and after 1 month in six rabbits. Immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), choline acetyltransferase (ChAT), and synaptophysin (SYN) was performed to determine the magnitude of Nerve Sprouting. Tissues from six normal rabbits were used as controls. Nerve density was determined by computerized morphometry. Results Myocardial infarction results in increased serum NGF levels at 1 week (1519.8±632.2 ng/ml) that persist up to 1 month (1361.2±176.3 ng/ml) as compared to controls (89.6±34.9 ng/ml) (P=.0002 and P=.0001, respectively). Immunostaining demonstrated Nerve Sprouting and hyperinnervation in both SGs after MI. The Nerve densities (μm2/ganglion cell) in SG 1 week after MI and 1 month after MI and those in control groups, respectively, were as follows: GAP43: 278±96, 225±39, and 149±57 (P=.01); SYN: 244±152, 268±115, and 102±60 (P=.02); TH: 233±71, 180±50, and 135±68 (P=.047); ChAT: 244±100, 208±46, and 130±41 μm2/cell (P=.01). Conclusions Myocardial infarction increases serum NGF levels and induces Nerve Sprouting and hyperinnervation in bilateral SGs for at least 1 month after MI. The hyperinnervation includes both adrenergic axons and cholinergic axons in the SG.
Lan S. Chen - One of the best experts on this subject based on the ideXlab platform.
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Subcutaneous Nerve Stimulation Reduces Sympathetic Nerve Activity in Ambulatory Dogs with Myocardial Infarction
Heart Rhythm, 2020Co-Authors: Yuan Yuan, Michael C Fishbein, Ye Zhao, Johnson Wong, Wei-chung Tsai, Zhaolei Jiang, Ryan A. Kabir, Changyu Shen, Lan S. ChenAbstract:Background Subcutaneous Nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion Nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through Nerve Sprouting. Objective The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI. Methods In the experimental group, a radio transmitter was implanted during the first sterile surgery to record Nerve activity and an electrocardiogram, followed by a second sterile surgery to create MI. Dogs then underwent ScNS for 2 months. The average SGNA (aSGNA) was compared with that in a historical control group (n = 9), with acute MI monitored for 2 months without ScNS. Results In the experimental group, the baseline aSGNA and heart rate were 4.08±0.35 μV and 98±12 beats/min, respectively. They increased within 1 week after MI to 6.91±1.91 μV (P=.007) and 107±10 beats/min (P=.028), respectively. ScNS reduced aSGNA to 3.46±0.44 μV (P Conclusion ScNS remodels the stellate ganglion, reduces SGNA, and suppresses cardiac Nerve Sprouting after acute MI.
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Nerve Sprouting and Cardiac Arrhythmias
Cardiac Electrophysiology, 2013Co-Authors: Lan S. Chen, Peng-sheng ChenAbstract:After division, crushing, interference of blood supply, or other means of injury, the peripheral Nerves undergo Wallerian degeneration and axonal regeneration. This regenerative process, termed Nerve Sprouting , is well described, both in the central nervous system and in the peripheral nervous system. If the Nerve sprouts form synapses, they may result in permanent changes of local innervation, leading to functional consequences. Myocardial infarction (MI) causes Nerve injury and regional sympathetic denervation. Afterward, Nerve Sprouting occurs and results in a regional increase of sympathetic hyperinnervation. 1 Although the magnitude of Nerve Sprouting varies from subject to subject, there is a correlation between the density of sympathetic Nerve and occurrence of ventricular arrhythmia. 2 3 In this chapter, we will review the relationship between sympathetic Nerve Sprouting and cardiac arrhythmia.
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Nerve Sprouting defibrillation and calcium waves
2013Co-Authors: Mitsunori Maruyama, Lan S. Chen, Shengmei Zhou, Gyoseung Hwang, Su Kiat Chua, Po Cheng Chang, Tomohiko Ai, Peng-sheng ChenAbstract:Zoll et al. first reported the successful termination of ventricular fibrillation (VF) by externally applied electrical countershocks. In the same seminal report, the authors also discovered that recurrent VF may occur shortly after successful ventricular defibrillation. Due to the general availability of the implantable cardioverter-defibrillator (ICD), patients may survive the initial VF episodes but suffer from multiple recurrent VF and defibrillation shocks within a short period of time. The clustering of recurrent VF episodes (electrical storm) after initial successful defibrillation suggests that the first episode of VF begets subsequent episodes of VF. The mechanisms by which VF begets VF remains poorly understood. In this chapter we will discuss the mechanisms of neural remodeling after myocardial infarction (MI). We propose that Nerve Sprouting and sympathetic hyperinnervation occur after MI. The increased sympathetic Nerve densities in the heart is highly heterogeneous, with portions of the heart showing increased Nerve densities while the remaining portions of the heart showing denervation. During sympathetic Nerve activation, there is increased heart rate and augmented intracellular calcium (Cai) concentration. In addition, we found that the action potential duration (APD) is abbreviated after a fibrillation-defibrillation episode in failing ventricles. The shortened APD and the elevated Cai promotes late phase 3 early afterdepolarization (EAD) and Ca2+-transient triggered firing (CTTF), leading to recurrent cardiac fibrillation. We also propose that the mechanisms of APD shortening after fibrillation-defibrillation episodes in the failing (but not in the normal) ventricles are due to the upregulation of small conductance Ca2+ activated potassium (SK) currents. We hope that these discussions will help the readers better understand the relevance of cardiac neural remodeling and electrical remodeling in the mechanisms of arrhythmogenesis.
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Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.
Cardiovascular Pathology, 2011Co-Authors: Bich Lien Nguyen, Michael C Fishbein, Peng-sheng Chen, Hongmei Li, Carlo Gaudio, Lan S. ChenAbstract:Abstract Introduction Myocardial infarction (MI) results in cardiac Nerve Sprouting in the myocardium. Whether or not similar neural remodeling occurs in the stellate ganglia (SGs) is unknown. We aimed to test the hypothesis that MI induces bilateral SG Nerve Sprouting. Methods Acute MI was created by coronary artery ligation in rabbits (n=12). Serum Nerve growth factor (NGF) level was measured by enzyme-linked immunosorbent assay. The hearts and bilateral SGs were harvested for immunohistochemistry after 1 week in six rabbits and after 1 month in six rabbits. Immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), choline acetyltransferase (ChAT), and synaptophysin (SYN) was performed to determine the magnitude of Nerve Sprouting. Tissues from six normal rabbits were used as controls. Nerve density was determined by computerized morphometry. Results Myocardial infarction results in increased serum NGF levels at 1 week (1519.8±632.2 ng/ml) that persist up to 1 month (1361.2±176.3 ng/ml) as compared to controls (89.6±34.9 ng/ml) (P=.0002 and P=.0001, respectively). Immunostaining demonstrated Nerve Sprouting and hyperinnervation in both SGs after MI. The Nerve densities (μm2/ganglion cell) in SG 1 week after MI and 1 month after MI and those in control groups, respectively, were as follows: GAP43: 278±96, 225±39, and 149±57 (P=.01); SYN: 244±152, 268±115, and 102±60 (P=.02); TH: 233±71, 180±50, and 135±68 (P=.047); ChAT: 244±100, 208±46, and 130±41 μm2/cell (P=.01). Conclusions Myocardial infarction increases serum NGF levels and induces Nerve Sprouting and hyperinnervation in bilateral SGs for at least 1 month after MI. The hyperinnervation includes both adrenergic axons and cholinergic axons in the SG.
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atrial sympathetic and parasympathetic Nerve Sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs
Cardiovascular Pathology, 2008Co-Authors: Moshe Swissa, Michael C Fishbein, Shengmei Zhou, Peng-sheng Chen, Lan S. ChenAbstract:Abstract Background Subthreshold electrical stimulation of the left stellate ganglion (LSG) can induce Nerve Sprouting and sympathetic hyperinnervation in canine ventricles. It is unclear whether a similar neural plasticity involving both sympathetic and parasympathetic innervation also exists in the atria. Methods and Results We applied subthreshold electrical stimulation at 20 Hz (0.45 ms pulse width) or 5 Hz (1.9 ms pulse width) to the LSG in 6 normal mongrel dogs. After 41±9 days, the hearts were harvested and the right and left atrium stained for synaptophysin (SYN), growth-associated protein 43 (GAP43), sympathetic Nerve markers tyrosine hydroxylase (TH), and parasympathetic marker choline acetyltransferase (ChAT). Tissues from 6 additional healthy dogs were used as controls. The hearts from dogs with LSG electrical stimulation had a higher density of Nerve structures immunopositive to the SYN, GAP43, TH, and ChAT ( P P Conclusions Continuous subthreshold electrical stimulation to the LSG induces both sympathetic and parasympathetic hyperinnervation in both right and left atria in normal dogs.
Hrayr S Karagueuzian - One of the best experts on this subject based on the ideXlab platform.
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spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic Nerve Sprouting
Journal of Cardiovascular Electrophysiology, 2012Co-Authors: M Ayaka D Numata, C Michael M D Fishbein, M Pengsheng D Chen, M Yasushi D Miyauchi, J William M D Mandel, N James M D Weiss, Hrayr S KaragueuzianAbstract:Sympathetic Activation and Atrial Fibrillation. Background: Chronic left ventricular myocardial infarction (LVMI) promotes atrial and pulmonary veins (PV) sympathetic Nerve Sprouting. Objectives: To test the hypothesis that sympathetic stimulation with tyramine initiates atrial fibrillation (AF) by early afterdepolarization (EAD)-mediated triggered activity at the left atrial PV (LAPV) junction. Methods: LVMI was created in 6 dogs and 6 dogs served as controls. Six to 8 weeks later the activation pattern of the isolated LAPV was optically mapped using dual voltage and intracellular Ca+2 (Cai2+)-sensitive epifluorescent dyes before and after tyramine (5 μM) perfusion. Results: Tyramine initiated spontaneous AF in 5 of 6 atria but none in the control group (P < 0.01). The AF was initiated by late phase 3 EAD-mediated triggered activity that arose from the LAPV junction causing functional conduction block in LA, reentry, and AF. The AF was subsequently maintained by mixed reentrant and focal mechanisms. The EADs arose during the late phase 3, when the Cai2+ level was 64 ± 12% of the peak systolic Cai2+ transient amplitude, a property caused by tyramine's simultaneous shortening of the action potential duration and lengthening of the Cai2+ transient duration in the LVMI group but not in the control. Tyrosine hydroxylase and growth associated protein 43 positive Nerve sprouts were significantly increased in the sinus node, LAA, and the LSPV in the LVMI group compared to control (P < 0.01). Conclusions: Increased atrial sympathetic Nerve sprouts after LVMI makes the LAPV junction susceptible to late phase 3 EAD-mediated triggered and AF during sympathetic stimulation with tyramine.
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Nerve Sprouting induced by radiofrequency catheter ablation in dogs
Heart Rhythm, 2004Co-Authors: Yuji Okuyama, Michael C Fishbein, Hrayr S Karagueuzian, Yasushi Miyauchi, Chung Chuan Chou, Hideki Hayashi, Katherine J Fu, Walter F Kerwin, Cary Hata, Peng-sheng ChenAbstract: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 μm 2 /mm 2 ) and in 1 month (2,948 ± 666 μm 2 /mm 2 ) after ablation compared to controls (1,377 ± 471 μm 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 ± 3241μm 2 /mm 2 ) and the chronic group (6,030 ± 2226 μm 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 μm 2 /mm 2 , P = .0136) that was reduced down to the normal control level (722 ± 337 μm 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.
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induction of atrial fibrillation and Nerve Sprouting by prolonged left atrial pacing in dogs
Pacing and Clinical Electrophysiology, 2003Co-Authors: Hamabe Akira, Shengmei Zhou, Michael C Fishbein, Hrayr S Karagueuzian, Yuji Okuyama, Yasushi Miyauchi, Chung Chuan Chou, Che Ming Chang, Johnny Yi, Lan S. ChenAbstract:: The authors hypothesized that rapid electrical stimulation can induce Nerve Sprouting in canine atria, and that LA pacing is more effective than RA pacing in inducing sustained AF. Chronic rapid (20 Hz) LA epicardial pacing was performed in six dogs. Sustained AF (>48 hours) was induced within 23 +/- 8 days, which was much faster than that with RA endocardial pacing using the same protocol (139 +/- 84 days, P < 0.05). Nerves were identified by immunocytochemical techniques. In all dogs, growth-associated protein 43-positive (Sprouting) Nerve density was highest near the pacing site, and the rapid LA pacing resulted in differential Nerve Sprouting among the LA, left superior pulmonary vein (LSPV), interatrial septum (IAS), and RA (5521 +/- 1496, 3154 +/- 2355, 3953 +/- 1164, 1559 +/- 1077 microm2/mm2, respectively, P = 0.0032). Tyrosine hydroxylase-positive (sympathetic) Nerve density were not significantly different among groups (2726 +/- 1165, 1586 +/- 558, 2156 +/- 1741, 1509 +/- 1242 microm2/mm2, respectively). The Nerves were inhomogeneously distributed. LA epicardial pacing induced sustained AF much faster than RA endocardial pacing and rapid electrical stimulation can induce inhomogeneous Nerve Sprouting near the pacing site.
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Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death.
Journal of the American College of Cardiology, 2003Co-Authors: Moshe Swissa, Shengmei Zhou, Michael C Fishbein, Peng-sheng Chen, Hrayr S Karagueuzian, Che Ming Chang, Ignacio Gonzalez-gomez, Adam W. Cates, Lan S. ChenAbstract: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 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.
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modulation of qt interval by cardiac sympathetic Nerve Sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death
Journal of Cardiovascular Electrophysiology, 2001Co-Authors: M Shengmei D Zhou, Bruce H Kenknight, Hrayr S Karagueuzian, Zachary D Tebb, M Toshihiko D Ohara, A Hsunlun B S Huang, M Chikaya D Omichi, S Lan M D Chen, C Michael M D Fishbein, M Pengsheng D ChenAbstract:QT Interval and Sudden Cardiac Death.Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and Nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time-dependent increase of QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 ± 41 msec) were significantly longer than those in the control (350 ± 41 msec; P < 0.05) and RSG groups (294 ± 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic Nerve Sprouting and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with Nerve Sprouting, MI, and CAVB.
Behrooz G Sharifi - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of cardiac Nerve Sprouting after myocardial infarction in dogs
Circulation Research, 2004Co-Authors: Shengmei Zhou, Lan S. Chen, Michael C Fishbein, Yasushi Miyauchi, Behrooz G Sharifi, Mizuho Miyauchi, Simon Kangavari, Peng-sheng ChenAbstract: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
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mesenchymal stem cell injection induces cardiac Nerve Sprouting and increased tenascin expression in a swine model of myocardial infarction
Journal of Cardiovascular Electrophysiology, 2003Co-Authors: Mohammed Qayyum, Behrooz G Sharifi, S Lan M D Chen, C Michael M D Fishbein, M Yasushi D Miyauchi, M Akira D Hamabe, C Michael M D Lill, M Malkar S Frantzen, M Kaname D Takizawa, M Pengsheng D ChenAbstract:Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac Nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for Nerve density. The results show the following. (1) There were more GAP43-positive Nerves in the MSC group than in the BM, MI-only, or Control group (P < 0.0001). TH staining showed higher Nerve densities in the MSC group than in the MI-only (P < 0.01) or Control group (P < 0.0001) in the atria. (2) There were more sympathetic (TH-positive) Nerves in myocardium distant from infarct than in the peri-infarct area (P < 0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P < 0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac Nerve Sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection. (J Cardiovasc Electrophysiol, Vol. 14, pp. 841-848, August 2003)
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sympathetic Nerve Sprouting electrical remodeling and the mechanisms of sudden cardiac death
Cardiovascular Research, 2001Co-Authors: Peng-sheng Chen, Lan S. Chen, Hrayr S Karagueuzian, Behrooz G Sharifi, Michael C FishbeinAbstract:The purpose of this article is to review the Nerve Sprouting hypothesis of sudden cardiac death. It is known that sympathetic stimulation is important in the generation of sudden cardiac death. For example, there is a diurnal variation of sudden death rate in patients with myocardial infarction. Beta blockers, or drugs with beta blocking effects, are known to prevent sudden cardiac death. It was unclear if the cardiac Nerves in the heart play only a passive role in the mechanisms of sudden death. To determine if Nerve Sprouting and neural remodeling occur after myocardial infarction, we performed immunocytochemical studies of cardiac Nerves in explanted native hearts of transplant recipients. We found that there was a positive correlation between Nerve density and a clinical history of ventricular arrhythmia. Encouraged by these results, we performed a study in dogs to determine whether or not Nerve growth factor (NGF) infusion to the left stellate ganglion can facilitate the development of ventricular tachycardia (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD). The results showed that augmented myocardial sympathetic Nerve Sprouting through NGF infusion plus atrioventricular (AV) block and MI result in a 44% incidence (four of nine dogs) of SCD and a high incidence of VT in the chronic phase of MI. In contrast, none of the six dogs (with AV block and MI) without NGF infusion died suddenly or had frequent VT episodes. Based on these findings, we propose the Nerve Sprouting hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI results in Nerve injury, followed by sympathetic Nerve Sprouting and regional (heterogeneous) myocardial hyperinnervation. The coupling between augmented sympathetic Nerve Sprouting with electrically remodeled myocardium results in VT, VF and SCD. Modification of Nerve Sprouting after MI may provide a novel opportunity for arrhythmia control.
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colocalization of tenascin and sympathetic Nerves in a canine model of Nerve Sprouting and sudden cardiac death
Journal of Cardiovascular Electrophysiology, 2000Co-Authors: Kurt Wallner, Lan S. Chen, Michael C Fishbein, Peng-sheng Chen, Hrayr S Karagueuzian, Behrooz G SharifiAbstract:Tenascin and Cardiac Nerve Sprouting. Introduction: Sympathetic Nerve Sprouting after myocardial infarction (MI) may contribute significantly to the occurrence of ventricular arrhythmia and sudden cardiac death. Tenascin-X (TnX), a matrix protein known to be associated with Nerve growth in central and peripheral Nerves, also may play a role in cardiac Nerve Sprouting after MI. Methods and Results: Immunocytochemical staining techniques were used to identify Nerves in 5-μm serial sections from 6 normal dogs and 11 dogs with MI. Among the dogs with MI, 4 also received Nerve growth factor infusion to the left stellate ganglion. The time between MI to tissue harvest averaged 35.7 ± 14.4 days. Tyrosine hydroxylase (TH) stain was used to identify sympathetic Nerves, and growth-associated protein-43 (GAP-43) was used to identify growing Nerves. Polyclonal antibody was obtained for use in identifying TnX. Nerves were evident in both the infarcted and noninfarcted areas. Many Nerves were found around blood vessels. A total of 181 Nerves in 69 slides were examined: 89 were from noninfarcted myocardium, 4 from infarct, 13 from infarct horder zone, and 75 from perivascular regions. Except in normal dogs, all Nerves stained positive for TH also stained positive for GAP-43, indicating sympathetic Nerve Sprouting after MI. In all dogs, the Nerves that stained positive for TH also stained positive for TnX. Conclusion: There is a colocalization of TnX, GAP-43, and TH in sprouted cardiac Nerves. These results suggest that TnX is important not only in the existing normal myocardial Nerve cells but also in cardiac sympathetic Nerve Sprouting after MI.