The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Simon J Fisher - One of the best experts on this subject based on the ideXlab platform.
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severe hypoglycemia induced fatal cardiac arrhythmias are mediated by the Parasympathetic Nervous System in rats
Diabetes, 2019Co-Authors: Candace M Reno, Justin Bayles, Yiqing Huang, Milan Oxspring, Annie M Hirahara, Derek J Dosdall, Simon J FisherAbstract:The contribution of the sympathetic Nervous System (SNS) versus the Parasympathetic Nervous System (PSNS) in mediating fatal cardiac arrhythmias during insulin-induced severe hypoglycemia is not well understood. Therefore, experimental protocols were performed in nondiabetic Sprague-Dawley rats to test the SNS with 1) adrenal demedullation and 2) chemical sympathectomy, and to test the PSNS with 3) surgical vagotomy, 4) nicotinic receptor (mecamylamine) and muscarinic receptor (AQ-RA 741) blockade, and 5) ex vivo heart perfusions with normal or low glucose, acetylcholine (ACh), and/or mecamylamine. In protocols 1–4, 3-h hyperinsulinemic (0.2 units/kg/min) and hypoglycemic (10–15 mg/dL) clamps were performed. Adrenal demedullation and chemical sympathectomy had no effect on mortality or arrhythmias during severe hypoglycemia compared with controls. Vagotomy led to a 6.9-fold decrease in mortality; reduced first- and second-degree heart block 4.6- and 4-fold, respectively; and prevented third-degree heart block compared with controls. Pharmacological blockade of nicotinic receptors, but not muscarinic receptors, prevented heart block and mortality versus controls. Ex vivo heart perfusions demonstrated that neither low glucose nor ACh alone caused arrhythmias, but their combination induced heart block that could be abrogated by nicotinic receptor blockade. Taken together, ACh activation of nicotinic receptors via the vagus nerve is the primary mediator of severe hypoglycemia–induced fatal cardiac arrhythmias.
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385 p blocking the nicotinic receptors of the Parasympathetic Nervous System prevents severe hypoglycemia induced fatal cardiac arrhythmias in rats
Diabetes, 2019Co-Authors: Candace M Reno, Justin Bayles, Yiqing Huang, Milan Oxspring, Simon J FisherAbstract:In response to hypoglycemia, excessive stimulation of the Parasympathetic Nervous System (PNS) may induce bradycardia and fatal heart block. Since signaling via nicotinic receptors mediates the PNS response, it was hypothesized that these receptors may mediate hypoglycemia-induced cardiac arrhythmias. To test this hypothesis, mecamylamine (a nicotinic receptor antagonist; 7.5 mg/kg, n = 17) or saline (control; n = 20) was infused intravenously in Sprague Dawley rats during insulin-induced (0.2mU/kg/min) severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with electrocardiogram recordings. Compared to controls, mecamylamine-treated rats required a 3-fold higher glucose infusion rate during severe hypoglycemia, consistent with lower peak epinephrine levels (5698±557 vs. 2418±396 pg/ml; p In summary, blocking nicotinic receptors prevents cardiac arrhythmias and mortality during severe hypoglycemia. Clinically, targeting the Parasympathetic Nervous System could be a logical approach to prevent sudden death in people with insulin-treated diabetes at risk for hypoglycemia. Disclosure C.M. Reno: None. J. Bayles: None. Y. Huang: None. M.B. Oxspring: None. S. Fisher: None. Funding National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; JDRF
Judith L Black - One of the best experts on this subject based on the ideXlab platform.
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Endothelin-3 increases transmission in the rabbit pulmonary Parasympathetic Nervous System.
Journal of cardiovascular pharmacology, 1993Co-Authors: K O Mckay, Carol L Armour, Judith L BlackAbstract:The effect of endothelin-3 (ET-3) on the response to Parasympathetic nerve stimulation of rabbit isolated bronchus was examined. The site of action of ET-3 in the pulmonary Parasympathetic Nervous System was also investigated. ET-3 induced a concentration-dependent increase in the response to electrical field stimulation. The response was atropine sensitive and therefore cholinergically mediated. At a concentration of 10 nM, ET-3 increased the response to field stimulation to 205 +/- 42% of the initial response. The effect was concentration-related, as 100 nM further increased this response to 315 +/- 69%. The responsiveness of the tissue to exogenous acetylcholine was not affected by ET-3. Therefore ET-3 has a neuromodulatory role on cholinergic Parasympathetic transmission in rabbit airways exerted at a prejunctional site.
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endothelin 3 increases transmission in the rabbit pulmonary Parasympathetic Nervous System
Journal of Cardiovascular Pharmacology, 1993Co-Authors: Karen Mckay, Carol L Armour, Judith L BlackAbstract:The effect of endothelin-3 (ET-3) on the response to Parasympathetic nerve stimulation of rabbit isolated bronchus was examined. The site of action of ET-3 in the pulmonary Parasympathetic Nervous System was also investigated. ET-3 induced a concentration-dependent increase in the response to electrical field stimulation. The response was atropine sensitive and therefore cholinergically mediated. At a concentration of 10 nM, ET-3 increased the response to field stimulation to 205± 42% of the initial response. The effect was concentration-related, as 100 nM further increased this response to 315 ±69%. The responsiveness of the tissue to exogenous acetylcholine was not affected by ET-3
Wilson S. Colucci - One of the best experts on this subject based on the ideXlab platform.
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the Parasympathetic Nervous System and heart failure pathophysiology and potential therapeutic modalities for heart failure
2015Co-Authors: Brian Olshansky, Wilson S. Colucci, Renee M Sullivan, Hani N. SabbahAbstract:Congestive heart failure is associated with essential perturbations in the autonomic Nervous System. Early in the development of heart failure, there may be defective Parasympathetic cardiac control. This may occur before, or in parallel with, elevation in sympathetic tone. Here, we consider alterations that occur in the Parasympathetic Nervous System during the initiation and development of congestive heart failure. We also consider targets in the Parasympathetic Nervous System at various levels that may affect and improve clinical outcomes (survival, measures of progressive heart failure and debilitation, and cardiac remodeling, to name a few) by unique mechanistic effects that the Parasympathetic Nervous System exerts on heart rate, inflammation, remodeling, endothelial nitric oxide synthase activity, inhibition of the sympathetic Nervous System, and other potential mechanisms. We consider approaches to vagus nerve stimulation, the designs and early outcomes of trials, and some of the drug interventions that have been attempted. In this rapidly emerging field, with little clinical data, we discuss issues regarding study designs and outcome measures of importance.
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Parasympathetic Nervous System and heart failure pathophysiology and potential implications for therapy
Circulation, 2008Co-Authors: Brian Olshansky, Paul J Hauptman, Hani N. Sabbah, Wilson S. ColucciAbstract:Abundant evidence links sympathetic Nervous System activation to outcomes of patients with heart failure (HF).1 In contrast, Parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized. In particular, the pathophysiological roles of normal and disordered Parasympathetic innervation in patients with HF are not understood as comprehensively.2–5 In the present article, we review cardiovascular responses to Parasympathetic activation, address the modulating factors that can affect Parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the Parasympathetic Nervous System may have important therapeutic implications for patients with congestive HF. The Parasympathetic Nervous System originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus. Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors. Postganglionic Parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure).6–8 Figure. Parasympathetic and sympathetic innervation of the heart: anatomy. Efferent fiber (vagus) comprises A-beta, A-delta, and unmyelinated C fibers. Reproduced from Martini FH. Fundamentals of Anatomy and Physiology . 8th ed. 2006. Chapter 20, by permission of Pearson Education, Inc Prentice Hall, copyright © 2006. Vagus nerve afferent activation, originating peripherally, can modulate efferent sympathetic and Parasympathetic function centrally and at the level of the baroreceptor. Efferent vagus nerve activation can have tonic and basal effects that inhibit sympathetic activation and release of norepinephrine at the presynaptic level. Acetylcholine release from Parasympathetic nerve terminals will activate ganglionic nicotinic receptors that in turn activate muscarinic receptors at the cellular level. Cardiovascular effects include heart rate reduction by inhibition of the sympathetic Nervous System and by direct hyperpolarization of sinus nodal cells. Parasympathetic activation …
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Parasympathetic Nervous System and heart failure pathophysiology and potential implications for therapy
Circulation, 2008Co-Authors: Brian Olshansky, Paul J Hauptman, Hani N. Sabbah, Wilson S. ColucciAbstract:Image
Brian Olshansky - One of the best experts on this subject based on the ideXlab platform.
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the Parasympathetic Nervous System and heart failure pathophysiology and potential therapeutic modalities for heart failure
2015Co-Authors: Brian Olshansky, Wilson S. Colucci, Renee M Sullivan, Hani N. SabbahAbstract:Congestive heart failure is associated with essential perturbations in the autonomic Nervous System. Early in the development of heart failure, there may be defective Parasympathetic cardiac control. This may occur before, or in parallel with, elevation in sympathetic tone. Here, we consider alterations that occur in the Parasympathetic Nervous System during the initiation and development of congestive heart failure. We also consider targets in the Parasympathetic Nervous System at various levels that may affect and improve clinical outcomes (survival, measures of progressive heart failure and debilitation, and cardiac remodeling, to name a few) by unique mechanistic effects that the Parasympathetic Nervous System exerts on heart rate, inflammation, remodeling, endothelial nitric oxide synthase activity, inhibition of the sympathetic Nervous System, and other potential mechanisms. We consider approaches to vagus nerve stimulation, the designs and early outcomes of trials, and some of the drug interventions that have been attempted. In this rapidly emerging field, with little clinical data, we discuss issues regarding study designs and outcome measures of importance.
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Parasympathetic Nervous System and heart failure pathophysiology and potential implications for therapy
Circulation, 2008Co-Authors: Brian Olshansky, Paul J Hauptman, Hani N. Sabbah, Wilson S. ColucciAbstract:Abundant evidence links sympathetic Nervous System activation to outcomes of patients with heart failure (HF).1 In contrast, Parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized. In particular, the pathophysiological roles of normal and disordered Parasympathetic innervation in patients with HF are not understood as comprehensively.2–5 In the present article, we review cardiovascular responses to Parasympathetic activation, address the modulating factors that can affect Parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the Parasympathetic Nervous System may have important therapeutic implications for patients with congestive HF. The Parasympathetic Nervous System originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus. Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors. Postganglionic Parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure).6–8 Figure. Parasympathetic and sympathetic innervation of the heart: anatomy. Efferent fiber (vagus) comprises A-beta, A-delta, and unmyelinated C fibers. Reproduced from Martini FH. Fundamentals of Anatomy and Physiology . 8th ed. 2006. Chapter 20, by permission of Pearson Education, Inc Prentice Hall, copyright © 2006. Vagus nerve afferent activation, originating peripherally, can modulate efferent sympathetic and Parasympathetic function centrally and at the level of the baroreceptor. Efferent vagus nerve activation can have tonic and basal effects that inhibit sympathetic activation and release of norepinephrine at the presynaptic level. Acetylcholine release from Parasympathetic nerve terminals will activate ganglionic nicotinic receptors that in turn activate muscarinic receptors at the cellular level. Cardiovascular effects include heart rate reduction by inhibition of the sympathetic Nervous System and by direct hyperpolarization of sinus nodal cells. Parasympathetic activation …
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Parasympathetic Nervous System and heart failure pathophysiology and potential implications for therapy
Circulation, 2008Co-Authors: Brian Olshansky, Paul J Hauptman, Hani N. Sabbah, Wilson S. ColucciAbstract:Image
Candace M Reno - One of the best experts on this subject based on the ideXlab platform.
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severe hypoglycemia induced fatal cardiac arrhythmias are mediated by the Parasympathetic Nervous System in rats
Diabetes, 2019Co-Authors: Candace M Reno, Justin Bayles, Yiqing Huang, Milan Oxspring, Annie M Hirahara, Derek J Dosdall, Simon J FisherAbstract:The contribution of the sympathetic Nervous System (SNS) versus the Parasympathetic Nervous System (PSNS) in mediating fatal cardiac arrhythmias during insulin-induced severe hypoglycemia is not well understood. Therefore, experimental protocols were performed in nondiabetic Sprague-Dawley rats to test the SNS with 1) adrenal demedullation and 2) chemical sympathectomy, and to test the PSNS with 3) surgical vagotomy, 4) nicotinic receptor (mecamylamine) and muscarinic receptor (AQ-RA 741) blockade, and 5) ex vivo heart perfusions with normal or low glucose, acetylcholine (ACh), and/or mecamylamine. In protocols 1–4, 3-h hyperinsulinemic (0.2 units/kg/min) and hypoglycemic (10–15 mg/dL) clamps were performed. Adrenal demedullation and chemical sympathectomy had no effect on mortality or arrhythmias during severe hypoglycemia compared with controls. Vagotomy led to a 6.9-fold decrease in mortality; reduced first- and second-degree heart block 4.6- and 4-fold, respectively; and prevented third-degree heart block compared with controls. Pharmacological blockade of nicotinic receptors, but not muscarinic receptors, prevented heart block and mortality versus controls. Ex vivo heart perfusions demonstrated that neither low glucose nor ACh alone caused arrhythmias, but their combination induced heart block that could be abrogated by nicotinic receptor blockade. Taken together, ACh activation of nicotinic receptors via the vagus nerve is the primary mediator of severe hypoglycemia–induced fatal cardiac arrhythmias.
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385 p blocking the nicotinic receptors of the Parasympathetic Nervous System prevents severe hypoglycemia induced fatal cardiac arrhythmias in rats
Diabetes, 2019Co-Authors: Candace M Reno, Justin Bayles, Yiqing Huang, Milan Oxspring, Simon J FisherAbstract:In response to hypoglycemia, excessive stimulation of the Parasympathetic Nervous System (PNS) may induce bradycardia and fatal heart block. Since signaling via nicotinic receptors mediates the PNS response, it was hypothesized that these receptors may mediate hypoglycemia-induced cardiac arrhythmias. To test this hypothesis, mecamylamine (a nicotinic receptor antagonist; 7.5 mg/kg, n = 17) or saline (control; n = 20) was infused intravenously in Sprague Dawley rats during insulin-induced (0.2mU/kg/min) severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with electrocardiogram recordings. Compared to controls, mecamylamine-treated rats required a 3-fold higher glucose infusion rate during severe hypoglycemia, consistent with lower peak epinephrine levels (5698±557 vs. 2418±396 pg/ml; p In summary, blocking nicotinic receptors prevents cardiac arrhythmias and mortality during severe hypoglycemia. Clinically, targeting the Parasympathetic Nervous System could be a logical approach to prevent sudden death in people with insulin-treated diabetes at risk for hypoglycemia. Disclosure C.M. Reno: None. J. Bayles: None. Y. Huang: None. M.B. Oxspring: None. S. Fisher: None. Funding National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; JDRF
