11 research outputs found
Study by atomic force microscopy and fluorescence microscopy of the interaction of silica nanoparticles with supported lipid films
Cette thĂšse sâinscrit dans le cadre des Ă©tudes portant sur la toxicitĂ© des nanoparticules (NPs). Leurs propriĂ©tĂ©s physico-chimiques confĂšrent aux NPs la capacitĂ© de pĂ©nĂ©trer dans les cellules en traversant la membrane plasmique. La comprĂ©hension de lâinteraction NPs-membrane est donc cruciale. La structure complexe des membranes nous a imposĂ© dâĂ©tudier lâinteraction NPs-membrane Ă lâaide de films lipidiques plans (monocouches et bicouches) utilisĂ©s comme modĂšles membranaires simplifiĂ©s, dĂ©posĂ©s sur des surfaces nanostructurĂ©es par le dĂ©pĂŽt prĂ©alable de NPs de silice (4 Ă 100 nm de diamĂštre) ou transfĂ©rĂ©s Ă partir de monocouches Ă©talĂ©es sur une suspension de NPs. Deux mĂ©thodes complĂ©mentaires ont Ă©tĂ© utilisĂ©es, la microscopie de force atomique (AFM) et la microscopie de fluorescence. AprĂšs une premiĂšre phase dâoptimisation des protocoles expĂ©rimentaux (choix des lipides, conditions de prĂ©paration des surfaces nanostructurĂ©es et des films), lâAFM a dâabord rĂ©vĂ©lĂ© lâoxydation des films monocouches constituĂ©s de lipides insaturĂ©s, se traduisant par la formation de domaines surĂ©levĂ©s par rapport Ă la phase lipidique intacte. Dans le cas des films de lipides prĂ©sentant une transition de phase de type liquide expansĂ©/liquide condensĂ©, la prĂ©sence des NPs (le plus souvent sous forme dâagrĂ©gats) semble favoriser la transition vers la phase condensĂ©e, les NPs Ă©tant situĂ©s soit au coeur soit en lisiĂšre des domaines condensĂ©s.Dans le cas des bicouches, lâĂ©tude par AFM en milieu liquide montre des comportements tribologiques diffĂ©rents des agrĂ©gats de NPs, suggĂ©rant deux organisations possibles de la bicouche lipidique, recouvrant les NPs ou formant des pores autour dâelles.The subject of this thesis fits into the large field of the toxicity of nanoparticles (NPs). Thanks to their physico-chemical properties, NPs are able to enter cells through the plasma membrane. Understanding the NPs-membrane interaction is thus very important. Membranes being complex structures, we chose to study this interaction using planar lipid films (monolayers and bilayers) as simplified membrane models, either deposited on nanostructured surfaces prepared by the prior deposition of silica NPs or transferred from monolayers spread on a subphase containing NPs (4-100 nm in diameter). Two complementary methods were used, atomic force microscopy (AFM) and fluorescence microscopy.After a first part devoted to the optimization of the experimental procedure (choice of lipids, design of nanostructured surfaces and films), AFM first revealed the oxidation of transferred monolayers made of unsaturated lipids, leading to the formation of domains raised above the intact lipid phase. In the case of films made of lipids characterized by a liquid expanded/liquid condensed phase transition, the presence of NPs (usually organized in aggregates) seems to favor the transition to the condensed phase, NPs being either embedded in condensed domains or at their edges.The final phase of this work was devoted to the study of NPs / bilayer interaction by AFM in liquid medium. The study shows different tribological behavior of NPs aggregates, suggesting two possible organizations of the lipid bilayer, covering the NPs or forming holes around them
Study by atomic force microscopy and fluorescence microscopy of the interaction of silica nanoparticles with supported lipid films
Cette thĂšse sâinscrit dans le cadre des Ă©tudes portant sur la toxicitĂ© des nanoparticules (NPs). Leurs propriĂ©tĂ©s physico-chimiques confĂšrent aux NPs la capacitĂ© de pĂ©nĂ©trer dans les cellules en traversant la membrane plasmique. La comprĂ©hension de lâinteraction NPs-membrane est donc cruciale. La structure complexe des membranes nous a imposĂ© dâĂ©tudier lâinteraction NPs-membrane Ă lâaide de films lipidiques plans (monocouches et bicouches) utilisĂ©s comme modĂšles membranaires simplifiĂ©s, dĂ©posĂ©s sur des surfaces nanostructurĂ©es par le dĂ©pĂŽt prĂ©alable de NPs de silice (4 Ă 100 nm de diamĂštre) ou transfĂ©rĂ©s Ă partir de monocouches Ă©talĂ©es sur une suspension de NPs. Deux mĂ©thodes complĂ©mentaires ont Ă©tĂ© utilisĂ©es, la microscopie de force atomique (AFM) et la microscopie de fluorescence. AprĂšs une premiĂšre phase dâoptimisation des protocoles expĂ©rimentaux (choix des lipides, conditions de prĂ©paration des surfaces nanostructurĂ©es et des films), lâAFM a dâabord rĂ©vĂ©lĂ© lâoxydation des films monocouches constituĂ©s de lipides insaturĂ©s, se traduisant par la formation de domaines surĂ©levĂ©s par rapport Ă la phase lipidique intacte. Dans le cas des films de lipides prĂ©sentant une transition de phase de type liquide expansĂ©/liquide condensĂ©, la prĂ©sence des NPs (le plus souvent sous forme dâagrĂ©gats) semble favoriser la transition vers la phase condensĂ©e, les NPs Ă©tant situĂ©s soit au coeur soit en lisiĂšre des domaines condensĂ©s.Dans le cas des bicouches, lâĂ©tude par AFM en milieu liquide montre des comportements tribologiques diffĂ©rents des agrĂ©gats de NPs, suggĂ©rant deux organisations possibles de la bicouche lipidique, recouvrant les NPs ou formant des pores autour dâelles.The subject of this thesis fits into the large field of the toxicity of nanoparticles (NPs). Thanks to their physico-chemical properties, NPs are able to enter cells through the plasma membrane. Understanding the NPs-membrane interaction is thus very important. Membranes being complex structures, we chose to study this interaction using planar lipid films (monolayers and bilayers) as simplified membrane models, either deposited on nanostructured surfaces prepared by the prior deposition of silica NPs or transferred from monolayers spread on a subphase containing NPs (4-100 nm in diameter). Two complementary methods were used, atomic force microscopy (AFM) and fluorescence microscopy.After a first part devoted to the optimization of the experimental procedure (choice of lipids, design of nanostructured surfaces and films), AFM first revealed the oxidation of transferred monolayers made of unsaturated lipids, leading to the formation of domains raised above the intact lipid phase. In the case of films made of lipids characterized by a liquid expanded/liquid condensed phase transition, the presence of NPs (usually organized in aggregates) seems to favor the transition to the condensed phase, NPs being either embedded in condensed domains or at their edges.The final phase of this work was devoted to the study of NPs / bilayer interaction by AFM in liquid medium. The study shows different tribological behavior of NPs aggregates, suggesting two possible organizations of the lipid bilayer, covering the NPs or forming holes around them
Etude par microscopie Ă force atomique et par microscopie de fluorescence de lâinteraction de nanoparticules de silice avec des films lipidiques plans
The subject of this thesis fits into the large field of the toxicity of nanoparticles (NPs). Thanks to their physico-chemical properties, NPs are able to enter cells through the plasma membrane. Understanding the NPs-membrane interaction is thus very important. Membranes being complex structures, we chose to study this interaction using planar lipid films (monolayers and bilayers) as simplified membrane models, either deposited on nanostructured surfaces prepared by the prior deposition of silica NPs or transferred from monolayers spread on a subphase containing NPs (4-100 nm in diameter). Two complementary methods were used, atomic force microscopy (AFM) and fluorescence microscopy.After a first part devoted to the optimization of the experimental procedure (choice of lipids, design of nanostructured surfaces and films), AFM first revealed the oxidation of transferred monolayers made of unsaturated lipids, leading to the formation of domains raised above the intact lipid phase. In the case of films made of lipids characterized by a liquid expanded/liquid condensed phase transition, the presence of NPs (usually organized in aggregates) seems to favor the transition to the condensed phase, NPs being either embedded in condensed domains or at their edges.The final phase of this work was devoted to the study of NPs / bilayer interaction by AFM in liquid medium. The study shows different tribological behavior of NPs aggregates, suggesting two possible organizations of the lipid bilayer, covering the NPs or forming holes around them.Cette thĂšse sâinscrit dans le cadre des Ă©tudes portant sur la toxicitĂ© des nanoparticules (NPs). Leurs propriĂ©tĂ©s physico-chimiques confĂšrent aux NPs la capacitĂ© de pĂ©nĂ©trer dans les cellules en traversant la membrane plasmique. La comprĂ©hension de lâinteraction NPs-membrane est donc cruciale. La structure complexe des membranes nous a imposĂ© dâĂ©tudier lâinteraction NPs-membrane Ă lâaide de films lipidiques plans (monocouches et bicouches) utilisĂ©s comme modĂšles membranaires simplifiĂ©s, dĂ©posĂ©s sur des surfaces nanostructurĂ©es par le dĂ©pĂŽt prĂ©alable de NPs de silice (4 Ă 100 nm de diamĂštre) ou transfĂ©rĂ©s Ă partir de monocouches Ă©talĂ©es sur une suspension de NPs. Deux mĂ©thodes complĂ©mentaires ont Ă©tĂ© utilisĂ©es, la microscopie de force atomique (AFM) et la microscopie de fluorescence. AprĂšs une premiĂšre phase dâoptimisation des protocoles expĂ©rimentaux (choix des lipides, conditions de prĂ©paration des surfaces nanostructurĂ©es et des films), lâAFM a dâabord rĂ©vĂ©lĂ© lâoxydation des films monocouches constituĂ©s de lipides insaturĂ©s, se traduisant par la formation de domaines surĂ©levĂ©s par rapport Ă la phase lipidique intacte. Dans le cas des films de lipides prĂ©sentant une transition de phase de type liquide expansĂ©/liquide condensĂ©, la prĂ©sence des NPs (le plus souvent sous forme dâagrĂ©gats) semble favoriser la transition vers la phase condensĂ©e, les NPs Ă©tant situĂ©s soit au coeur soit en lisiĂšre des domaines condensĂ©s.Dans le cas des bicouches, lâĂ©tude par AFM en milieu liquide montre des comportements tribologiques diffĂ©rents des agrĂ©gats de NPs, suggĂ©rant deux organisations possibles de la bicouche lipidique, recouvrant les NPs ou formant des pores autour dâelles
Study by atomic force microscopy and fluorescence microscopy of the interaction of silica nanoparticles with supported lipid films
Cette thĂšse sâinscrit dans le cadre des Ă©tudes portant sur la toxicitĂ© des nanoparticules (NPs). Leurs propriĂ©tĂ©s physico-chimiques confĂšrent aux NPs la capacitĂ© de pĂ©nĂ©trer dans les cellules en traversant la membrane plasmique. La comprĂ©hension de lâinteraction NPs-membrane est donc cruciale. La structure complexe des membranes nous a imposĂ© dâĂ©tudier lâinteraction NPs-membrane Ă lâaide de films lipidiques plans (monocouches et bicouches) utilisĂ©s comme modĂšles membranaires simplifiĂ©s, dĂ©posĂ©s sur des surfaces nanostructurĂ©es par le dĂ©pĂŽt prĂ©alable de NPs de silice (4 Ă 100 nm de diamĂštre) ou transfĂ©rĂ©s Ă partir de monocouches Ă©talĂ©es sur une suspension de NPs. Deux mĂ©thodes complĂ©mentaires ont Ă©tĂ© utilisĂ©es, la microscopie de force atomique (AFM) et la microscopie de fluorescence. AprĂšs une premiĂšre phase dâoptimisation des protocoles expĂ©rimentaux (choix des lipides, conditions de prĂ©paration des surfaces nanostructurĂ©es et des films), lâAFM a dâabord rĂ©vĂ©lĂ© lâoxydation des films monocouches constituĂ©s de lipides insaturĂ©s, se traduisant par la formation de domaines surĂ©levĂ©s par rapport Ă la phase lipidique intacte. Dans le cas des films de lipides prĂ©sentant une transition de phase de type liquide expansĂ©/liquide condensĂ©, la prĂ©sence des NPs (le plus souvent sous forme dâagrĂ©gats) semble favoriser la transition vers la phase condensĂ©e, les NPs Ă©tant situĂ©s soit au coeur soit en lisiĂšre des domaines condensĂ©s.Dans le cas des bicouches, lâĂ©tude par AFM en milieu liquide montre des comportements tribologiques diffĂ©rents des agrĂ©gats de NPs, suggĂ©rant deux organisations possibles de la bicouche lipidique, recouvrant les NPs ou formant des pores autour dâelles.The subject of this thesis fits into the large field of the toxicity of nanoparticles (NPs). Thanks to their physico-chemical properties, NPs are able to enter cells through the plasma membrane. Understanding the NPs-membrane interaction is thus very important. Membranes being complex structures, we chose to study this interaction using planar lipid films (monolayers and bilayers) as simplified membrane models, either deposited on nanostructured surfaces prepared by the prior deposition of silica NPs or transferred from monolayers spread on a subphase containing NPs (4-100 nm in diameter). Two complementary methods were used, atomic force microscopy (AFM) and fluorescence microscopy.After a first part devoted to the optimization of the experimental procedure (choice of lipids, design of nanostructured surfaces and films), AFM first revealed the oxidation of transferred monolayers made of unsaturated lipids, leading to the formation of domains raised above the intact lipid phase. In the case of films made of lipids characterized by a liquid expanded/liquid condensed phase transition, the presence of NPs (usually organized in aggregates) seems to favor the transition to the condensed phase, NPs being either embedded in condensed domains or at their edges.The final phase of this work was devoted to the study of NPs / bilayer interaction by AFM in liquid medium. The study shows different tribological behavior of NPs aggregates, suggesting two possible organizations of the lipid bilayer, covering the NPs or forming holes around them
Study by atomic force microscopy and fluorescence microscopy of the interaction of silica nanoparticles with supported lipid films
Cette thĂšse sâinscrit dans le cadre des Ă©tudes portant sur la toxicitĂ© des nanoparticules (NPs). Leurs propriĂ©tĂ©s physico-chimiques confĂšrent aux NPs la capacitĂ© de pĂ©nĂ©trer dans les cellules en traversant la membrane plasmique. La comprĂ©hension de lâinteraction NPs-membrane est donc cruciale. La structure complexe des membranes nous a imposĂ© dâĂ©tudier lâinteraction NPs-membrane Ă lâaide de films lipidiques plans (monocouches et bicouches) utilisĂ©s comme modĂšles membranaires simplifiĂ©s, dĂ©posĂ©s sur des surfaces nanostructurĂ©es par le dĂ©pĂŽt prĂ©alable de NPs de silice (4 Ă 100 nm de diamĂštre) ou transfĂ©rĂ©s Ă partir de monocouches Ă©talĂ©es sur une suspension de NPs. Deux mĂ©thodes complĂ©mentaires ont Ă©tĂ© utilisĂ©es, la microscopie de force atomique (AFM) et la microscopie de fluorescence. AprĂšs une premiĂšre phase dâoptimisation des protocoles expĂ©rimentaux (choix des lipides, conditions de prĂ©paration des surfaces nanostructurĂ©es et des films), lâAFM a dâabord rĂ©vĂ©lĂ© lâoxydation des films monocouches constituĂ©s de lipides insaturĂ©s, se traduisant par la formation de domaines surĂ©levĂ©s par rapport Ă la phase lipidique intacte. Dans le cas des films de lipides prĂ©sentant une transition de phase de type liquide expansĂ©/liquide condensĂ©, la prĂ©sence des NPs (le plus souvent sous forme dâagrĂ©gats) semble favoriser la transition vers la phase condensĂ©e, les NPs Ă©tant situĂ©s soit au coeur soit en lisiĂšre des domaines condensĂ©s.Dans le cas des bicouches, lâĂ©tude par AFM en milieu liquide montre des comportements tribologiques diffĂ©rents des agrĂ©gats de NPs, suggĂ©rant deux organisations possibles de la bicouche lipidique, recouvrant les NPs ou formant des pores autour dâelles.The subject of this thesis fits into the large field of the toxicity of nanoparticles (NPs). Thanks to their physico-chemical properties, NPs are able to enter cells through the plasma membrane. Understanding the NPs-membrane interaction is thus very important. Membranes being complex structures, we chose to study this interaction using planar lipid films (monolayers and bilayers) as simplified membrane models, either deposited on nanostructured surfaces prepared by the prior deposition of silica NPs or transferred from monolayers spread on a subphase containing NPs (4-100 nm in diameter). Two complementary methods were used, atomic force microscopy (AFM) and fluorescence microscopy.After a first part devoted to the optimization of the experimental procedure (choice of lipids, design of nanostructured surfaces and films), AFM first revealed the oxidation of transferred monolayers made of unsaturated lipids, leading to the formation of domains raised above the intact lipid phase. In the case of films made of lipids characterized by a liquid expanded/liquid condensed phase transition, the presence of NPs (usually organized in aggregates) seems to favor the transition to the condensed phase, NPs being either embedded in condensed domains or at their edges.The final phase of this work was devoted to the study of NPs / bilayer interaction by AFM in liquid medium. The study shows different tribological behavior of NPs aggregates, suggesting two possible organizations of the lipid bilayer, covering the NPs or forming holes around them
Weber's syndrome revealing a Percheron artery infarction: A case report
Key Clinical Message Weber's syndrome revealing a Percheron artery infarction is a rare clinical occurrence. Its diagnosis requires careful clinical examination and brain MRI, which is the gold standard for diagnosis. If this is not available, combined cerebral CT scan with a CT angiography of supraâaortic arteries may be useful for the diagnosis. Abstract Percheron's artery (PA) occlusion is an uncommon type of stroke involving paramedian thalamus and/or midbrain infarction. It accounts for 4%â18% of all thalamic infarcts and 0.1%â2% of all strokes. Its clinical manifestations are variable and its mode of presentation as Weber's syndrome is exceptional due to the unusual clinical presentation
Oxidation of Langmuir-Blodgett films of monounsaturated lipids studied by atomic force microscopy
In this work, we studied the stability in time of Langmuir-Blodgett films of POPC and OPPC, two unsaturated phospholipids with similar chains, differing by the relative position of these chains on the glycerol backbone. These films, transferred from the air-water interface onto freshly cleaved mica, were characterised by Atomic Force Microscopy (AFM) giving information on their topography at a lateral and perpendicular resolution in the nm range. AFM images (obtained in tapping mode) of freshly transferred films are homogenous, in agreement with the fact that these two lipids are in a liquid-expanded phase under our experimental conditions. After two days, small domains are observed, higher than the surrounding phase of about 0.8 nm in both types of samples. These domains are not observed if the samples are kept under vacuum, or if LB films are made of saturated phospholipids, suggesting that they are due to the local oxidation of POPC or OPPC, the oxidation being slightly more pronounced in the last case. Their dispersion in LB films suggests that oxidation occurs at different points at the same time, likely in areas presenting a loose packing or a defect. The local increase of thickness could be due to the reversal of the oxidised chain, raising the oxidised lipid above the surrounding phase
Influence of oxidized lipids on palmitoyl-oleoyl-phosphatidylcholine organization, contribution of Langmuir monolayers and LangmuirâBlodgett films
In this work, we studied the interaction of two oxidized lipids, PoxnoPC and PazePC, with POPC phospholipid. Mean molecular areas obtained from (ÏâA) isotherms of mixed PoxnoPCâPOPC and PazePCâPOPC monolayers revealed different behaviors of these two oxidized lipids: the presence of PoxnoPC in the monolayers induces their expansion, mean molecular areas being higher than those expected in the case of ideal mixtures. PazePCâPOPC behave on the whole ideally. This difference can be explained by a different conformation of oxidized lipids. Moreover the carboxylic function of PazePC is protonated under our experimental conditions, as shown by (ÏâA) isotherms of PazePC at different pH values. Both oxidized lipids induce also an increase of the monolayer elasticity, PoxnoPC being slightly more efficient than PazePC. These monolayers were transferred from the airâwater interface onto mica supports for a study by AFM. AFM images are on the whole homogenous, suggesting the presence of only one lipid phase in both cases. However, in the case of PazePCâPOPC monolayers, AFM images show also the presence of areas thicker of 7 nm to 10 nm than the surrounding lipid phase, probably due to the local formation of multilayer systems induced by compression
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Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract
BackgroundRight ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT.MethodsWe conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics.ResultsWe found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (P=0.003), whereas acetylcholine (100 ÎŒM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (P=0.034) and partially reversed action potential duration at 80% repolarization shortening (P=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (P=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT.ConclusionsHuman RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium
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Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract
BACKGROUND: Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT\u27s unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. METHODS: We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. RESULTS: We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (=0.003), whereas acetylcholine (100 ÎŒM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (=0.034) and partially reversed action potential duration at 80% repolarization shortening (=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. CONCLUSIONS: Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium