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F Berti - One of the best experts on this subject based on the ideXlab platform.

  • the aminotetraline derivative r s 5 6 dihydroxy 2 methylamino 1 2 3 4 tetrahydro naphthalene hydrochloride chf 1024 displays cardioprotection in postischemic ventricular dysfunction of the rat heart
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Giuseppe Rossoni, Barbara Manfredi, Viviana Cavalca, Roberta Razzetti, Stefano Bongrani, Gianluca Polvani, F Berti
    Abstract:

    To analyze the protective effects of the aminotetraline derivative (±)-( R , S )-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA 2 -dopaminergic/α 2 -adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of Cardiac ischemia in perfusate and tissue tumor necrosis factor-α (TNF-α). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F 1α The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic Nerve endings, and TNF-α from Cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from Cardiac Nerve endings may bear some therapeutic potential in cardiovascular diseases.

  • The aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024) displays cardioprotection in postischemic ventricular dysfunction of the rat heart
    'American Society for Pharmacology & Experimental Therapeutics (ASPET)', 2003
    Co-Authors: Giuseppe Rossoni, Barbara Manfredi, Viviana Cavalca, Roberta Razzetti, Stefano Bongrani, Gianluca Polvani, F Berti
    Abstract:

    To analyze the protective effects of the aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA2-dopaminergic/alpha2-adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of Cardiac ischemia in perfusate and tissue tumor necrosis factor-alpha (TNF-alpha). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F1alpha The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic Nerve endings, and TNF-alpha from Cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from Cardiac Nerve endings may bear some therapeutic potential in cardiovascular diseases

Nazareno Paolocci - One of the best experts on this subject based on the ideXlab platform.

  • cholinergic neurons of mouse intrinsic Cardiac ganglia contain noradrenergic enzymes norepinephrine transporters and the neurotrophin receptors tropomyosin related kinase a and p75
    Neuroscience, 2008
    Co-Authors: Jennifer L Hoard, Abigail M Mabe, Donald B Hoover, Randy D Blakely, Ning Feng, Nazareno Paolocci
    Abstract:

    Abstract Half of the cholinergic neurons of human and primate intrinsic Cardiac ganglia (ICG) have a dual cholinergic/noradrenergic phenotype. Likewise, a large subpopulation of cholinergic neurons of the mouse heart expresses enzymes needed for synthesis of norepinephrine (NE), but they lack the vesicular monoamine transporter type 2 (VMAT2) required for catecholamine storage. In the present study, we determined the full scope of noradrenergic properties (i.e. synthetic enzymes and transporters) expressed by cholinergic neurons of mouse ICG, estimated the relative abundance of neurons expressing different elements of the noradrenergic phenotype, and evaluated the colocalization of cholinergic and noradrenergic markers in atrial Nerve fibers. Stellate ganglia were used as a positive control for noradrenergic markers. Using fluorescence immunohistochemistry and confocal microscopy, we found that about 30% of cholinergic cell bodies contained tyrosine hydroxylase (TH), including the activated form that is phosphorylated at Ser-40 (pSer40 TH). Dopamine β-hydroxylase (DBH) and norepinephrine transporter (NET) were present in all cholinergic somata, indicating a wider capability for dopamine metabolism and catecholamine uptake. Yet, cholinergic somata lacked VMAT2, precluding the potential for NE storage and vesicular release. In contrast to cholinergic somata, Cardiac Nerve fibers rarely showed colocalization of cholinergic and noradrenergic markers. Instead, these labels were closely apposed but clearly distinct from each other. Since cholinergic somata expressed several noradrenergic proteins, we questioned whether these neurons might also contain trophic factor receptors typical of noradrenergic neurons. Indeed, we found that all cholinergic cell bodies of mouse ICG, like noradrenergic cell bodies of the stellate ganglia, contained both tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptors. Collectively, these findings demonstrate that mouse intrinsic Cardiac neurons (ICNs), like those of humans, have a complex neurochemical phenotype that goes beyond the classical view of Cardiac parasympathetic neurons. They also suggest that neurotrophins and local NE synthesis might have important effects on neurons of the mouse ICG.

  • cholinergic neurons of mouse intrinsic Cardiac ganglia contain noradrenergic enzymes norepinephrine transporters and the neurotrophin receptors tropomyosin related kinase a and p75
    Neuroscience, 2008
    Co-Authors: Jennifer L Hoard, Abigail M Mabe, Donald B Hoover, Randy D Blakely, Ning Feng, Nazareno Paolocci
    Abstract:

    Half of the cholinergic neurons of human and primate intrinsic Cardiac ganglia (ICG) have a dual cholinergic/noradrenergic phenotype. Likewise, a large subpopulation of cholinergic neurons of the mouse heart expresses enzymes needed for synthesis of norepinephrine (NE), but they lack the vesicular monoamine transporter type 2 (VMAT2) required for catecholamine storage. In the present study, we determined the full scope of noradrenergic properties (i.e. synthetic enzymes and transporters) expressed by cholinergic neurons of mouse ICG, estimated the relative abundance of neurons expressing different elements of the noradrenergic phenotype, and evaluated the colocalization of cholinergic and noradrenergic markers in atrial Nerve fibers. Stellate ganglia were used as a positive control for noradrenergic markers. Using fluorescence immunohistochemistry and confocal microscopy, we found that about 30% of cholinergic cell bodies contained tyrosine hydroxylase (TH), including the activated form that is phosphorylated at Ser-40 (pSer40 TH). Dopamine beta-hydroxylase (DBH) and norepinephrine transporter (NET) were present in all cholinergic somata, indicating a wider capability for dopamine metabolism and catecholamine uptake. Yet, cholinergic somata lacked VMAT2, precluding the potential for NE storage and vesicular release. In contrast to cholinergic somata, Cardiac Nerve fibers rarely showed colocalization of cholinergic and noradrenergic markers. Instead, these labels were closely apposed but clearly distinct from each other. Since cholinergic somata expressed several noradrenergic proteins, we questioned whether these neurons might also contain trophic factor receptors typical of noradrenergic neurons. Indeed, we found that all cholinergic cell bodies of mouse ICG, like noradrenergic cell bodies of the stellate ganglia, contained both tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptors. Collectively, these findings demonstrate that mouse intrinsic Cardiac neurons (ICNs), like those of humans, have a complex neurochemical phenotype that goes beyond the classical view of Cardiac parasympathetic neurons. They also suggest that neurotrophins and local NE synthesis might have important effects on neurons of the mouse ICG.

Michael C Fishbein - One of the best experts on this subject based on the ideXlab platform.

  • Antiarrhythmic and proarrhythmic effects of subcutaneous Nerve stimulation in ambulatory dogs.
    Heart Rhythm, 2019
    Co-Authors: Mu Chen, Maria B. Grant, Zhenhui Chen, Johnson Wong, Changyu Shen, Zhuo Wang, Michael C Fishbein, Thomas H Everett
    Abstract:

    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.

  • Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.
    Cardiovascular Pathology, 2011
    Co-Authors: Bich Lien Nguyen, Peng-sheng Chen, Carlo Gaudio, Hongmei Li, Michael C Fishbein, Lan S. Chen
    Abstract:

    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.

  • intrinsic Cardiac Nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs
    Circulation, 2010
    Co-Authors: Eue Keun Choi, Michael C Fishbein, Mark J Shen, Seongwook Han, Daehyeok Kim, Samuel Hwang, Sameh Sayfo, Gianfranco Piccirillo, Kyle Frick, Chun Hwang
    Abstract:

    Background— Little is known about the relationship between intrinsic Cardiac Nerve activity (ICNA) and spontaneous arrhythmias in ambulatory animals. Methods and Results— We implanted radiotransmitters to record extrinsic Cardiac Nerve activity (ECNA; including stellate ganglion Nerve activity and vagal Nerve activity) and ICNA (including superior left ganglionated plexi Nerve activity and ligament of Marshall Nerve activity) in 6 ambulatory dogs. Intermittent rapid left atrial pacing was performed to induce paroxysmal atrial fibrillation or atrial tachycardia. The vast majority (94%) of ligament of Marshall Nerve activity were preceded by or coactivated with ECNA (stellate ganglion Nerve activity or vagal Nerve activity), whereas 6% of episodes were activated alone without concomitant stellate ganglion Nerve activity or vagal Nerve activity. Paroxysmal atrial fibrillation and atrial tachycardia were invariably (100%) preceded (<5 seconds) by ICNA. Most paroxysmal atrial tachycardia events (89%) were prec...

  • 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, 2009
    Co-Authors: Brian H. Johnstone, Peng-sheng Chen, Todd G Cook, Michael C Fishbein, Keith L. March
    Abstract:

    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.

  • effects of omapatrilat on Cardiac Nerve sprouting and structural remodeling in experimental congestive heart failure
    Heart Rhythm, 2005
    Co-Authors: Margaret M Redfield, Sonia Shah, Win Kuang Shen, Michael C Fishbein, Peng-sheng Chen
    Abstract:

    Background Congestive heart failure (CHF) results in decreased Cardiac sympathetic innervation. Objectives The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates Cardiac neuronal remodeling in CHF. Methods We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n=8) or without (CHF group, n=10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine Cardiac structure and hemodynamic parameters. Myocardial Nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls. Results In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group ( P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high Nerve counts. OMA treatment prevented heterogeneous reduction of Nerve density. The left ventricular TH-positive Nerve densities were 128 ± 170 μm 2 /mm 2 , 261 ± 185 μm 2 /mm 2 , and 503 ± 328 μm 2 /mm 2 ( P 2 /mm 2 , 305 ± 368 μm 2 /mm 2 , and 1,278 ± 1,479 μm 2 /mm 2 ( P Conclusion CHF results in heterogeneous Cardiac denervation. Long-term OMA treatment prevented the reduction of Nerve density and promoted beneficial Cardiac structural remodeling.

Peng-sheng Chen - One of the best experts on this subject based on the ideXlab platform.

  • Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits.
    Cardiovascular Pathology, 2011
    Co-Authors: Bich Lien Nguyen, Peng-sheng Chen, Carlo Gaudio, Hongmei Li, Michael C Fishbein, Lan S. Chen
    Abstract:

    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.

  • 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, 2009
    Co-Authors: Brian H. Johnstone, Peng-sheng Chen, Todd G Cook, Michael C Fishbein, Keith L. March
    Abstract:

    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.

  • effects of omapatrilat on Cardiac Nerve sprouting and structural remodeling in experimental congestive heart failure
    Heart Rhythm, 2005
    Co-Authors: Margaret M Redfield, Sonia Shah, Win Kuang Shen, Michael C Fishbein, Peng-sheng Chen
    Abstract:

    Background Congestive heart failure (CHF) results in decreased Cardiac sympathetic innervation. Objectives The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates Cardiac neuronal remodeling in CHF. Methods We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n=8) or without (CHF group, n=10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine Cardiac structure and hemodynamic parameters. Myocardial Nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls. Results In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group ( P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high Nerve counts. OMA treatment prevented heterogeneous reduction of Nerve density. The left ventricular TH-positive Nerve densities were 128 ± 170 μm 2 /mm 2 , 261 ± 185 μm 2 /mm 2 , and 503 ± 328 μm 2 /mm 2 ( P 2 /mm 2 , 305 ± 368 μm 2 /mm 2 , and 1,278 ± 1,479 μm 2 /mm 2 ( P Conclusion CHF results in heterogeneous Cardiac denervation. Long-term OMA treatment prevented the reduction of Nerve density and promoted beneficial Cardiac structural remodeling.

  • Nerve sprouting induced by radiofrequency catheter ablation in dogs
    Heart Rhythm, 2004
    Co-Authors: Yuji Okuyama, Hrayr S Karagueuzian, Chung Chuan Chou, Katherine J Fu, Walter F Kerwin, Cary Hata, Yasushi Miyauchi, Hideki Hayashi, Michael C Fishbein, Peng-sheng Chen
    Abstract:

    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.

  • mechanisms of Cardiac Nerve sprouting after myocardial infarction in dogs
    Circulation Research, 2004
    Co-Authors: Shengmei Zhou, Lan S. Chen, Behrooz G Sharifi, Mizuho Miyauchi, Simon Kangavari, Yasushi Miyauchi, Michael C Fishbein, Peng-sheng Chen
    Abstract:

    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

Giuseppe Rossoni - One of the best experts on this subject based on the ideXlab platform.

  • the aminotetraline derivative r s 5 6 dihydroxy 2 methylamino 1 2 3 4 tetrahydro naphthalene hydrochloride chf 1024 displays cardioprotection in postischemic ventricular dysfunction of the rat heart
    Journal of Pharmacology and Experimental Therapeutics, 2003
    Co-Authors: Giuseppe Rossoni, Barbara Manfredi, Viviana Cavalca, Roberta Razzetti, Stefano Bongrani, Gianluca Polvani, F Berti
    Abstract:

    To analyze the protective effects of the aminotetraline derivative (±)-( R , S )-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA 2 -dopaminergic/α 2 -adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of Cardiac ischemia in perfusate and tissue tumor necrosis factor-α (TNF-α). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F 1α The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic Nerve endings, and TNF-α from Cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from Cardiac Nerve endings may bear some therapeutic potential in cardiovascular diseases.

  • The aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024) displays cardioprotection in postischemic ventricular dysfunction of the rat heart
    'American Society for Pharmacology & Experimental Therapeutics (ASPET)', 2003
    Co-Authors: Giuseppe Rossoni, Barbara Manfredi, Viviana Cavalca, Roberta Razzetti, Stefano Bongrani, Gianluca Polvani, F Berti
    Abstract:

    To analyze the protective effects of the aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA2-dopaminergic/alpha2-adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of Cardiac ischemia in perfusate and tissue tumor necrosis factor-alpha (TNF-alpha). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F1alpha The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic Nerve endings, and TNF-alpha from Cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from Cardiac Nerve endings may bear some therapeutic potential in cardiovascular diseases