4 results on '"Wang, Lianguo"'
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2. Different paths, same destination: divergent action potential responses produce conserved cardiac fight‐or‐flight response in mouse and rabbit hearts.
- Author
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Wang, Lianguo, Morotti, Stefano, Tapa, Srinivas, Francis Stuart, Samantha D., Jiang, Yanyan, Wang, Zhen, Myles, Rachel C., Brack, Kieran E., Ng, G. André, Bers, Donald M., Grandi, Eleonora, and Ripplinger, Crystal M.
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NEURAL stimulation , *RABBITS , *MICE , *CARDIAC output , *HEART beat - Abstract
Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. Sympathetic activation of the heart results in positive chronotropy and inotropy, which together rapidly increase cardiac output. The precise mechanisms that produce the electrophysiological and Ca2+ handling changes underlying chronotropic and inotropic responses have been studied in detail in isolated cardiac myocytes. However, few studies have examined the dynamic effects of physiological sympathetic nerve activation on cardiac action potentials (APs) and intracellular Ca2+ transients (CaTs) in the intact heart. Here, we performed bilateral sympathetic nerve stimulation (SNS) in fully innervated, Langendorff‐perfused rabbit and mouse hearts. Dual optical mapping with voltage‐ and Ca2+‐sensitive dyes allowed for analysis of spatio‐temporal AP and CaT dynamics. The rabbit heart responded to SNS with a monotonic increase in heart rate (HR), monotonic decreases in AP and CaT duration (APD, CaTD), and a monotonic increase in CaT amplitude. The mouse heart had similar HR and CaT responses; however, a pronounced biphasic APD response occurred, with initial prolongation (50.9 ± 5.1 ms at t = 0 s vs. 60.6 ± 4.1 ms at t = 15 s, P < 0.05) followed by shortening (46.5 ± 9.1 ms at t = 60 s, P = NS vs. t = 0). We determined the biphasic APD response in mouse was partly due to dynamic changes in HR during SNS and was exacerbated by β‐adrenergic activation. Simulations with species‐specific cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid CaT responses, suggesting more rapid increases in contractility; conversely, the rabbit heart requires APD shortening to produce optimal inotropic responses. Thus, while the cardiac fight‐or‐flight response is highly conserved between species, the underlying mechanisms orchestrating these effects differ significantly. Key points: Cardiac electrophysiology and Ca2+ handling change rapidly during the fight‐or‐flight response to meet physiological demands.Despite dramatic differences in cardiac electrophysiology, the cardiac fight‐or‐flight response is highly conserved across species.In this study, we performed physiological sympathetic nerve stimulation (SNS) while optically mapping cardiac action potentials and intracellular Ca2+ transients in innervated mouse and rabbit hearts.Despite similar heart rate and Ca2+ handling responses between mouse and rabbit hearts, we found notable species differences in spatio‐temporal repolarization dynamics during SNS.Species‐specific computational models revealed that these electrophysiological differences allowed for enhanced Ca2+ handling (i.e. enhanced inotropy) in each species, suggesting that electrophysiological responses are fine‐tuned across species to produce optimal cardiac fight‐or‐flight responses. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
3. Age‐related changes in cardiac electrophysiology and calcium handling in response to sympathetic nerve stimulation.
- Author
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Francis Stuart, Samantha D., Wang, Lianguo, Woodard, William R., Ng, G. Andre, Habecker, Beth A., and Ripplinger, Crystal M.
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CARDIOVASCULAR diseases , *CARDIAC arrest , *ELECTROPHYSIOLOGY , *NEURAL stimulation , *NEURODEGENERATION , *SYMPATHETIC nervous system - Abstract
Key points: Ageing results in changes to cardiac electrophysiology, Ca2+ handling, and β‐adrenergic responsiveness. Sympathetic neurodegeneration also occurs with age, yet detailed action potential and Ca2+ handling responses to physiological sympathetic nerve stimulation (SNS) in the aged heart have not been assessed. Optical mapping in mouse hearts with intact sympathetic innervation revealed reduced responsiveness to SNS in the aged atria (assessed by heart rate) and aged ventricles (assessed by action potentials and Ca2+ transients). Sympathetic nerve density and noradrenaline content were reduced in aged ventricles, but noradrenaline content was preserved in aged atria. These results demonstrate that reduced responsiveness to SNS in the atria may be primarily due to decreased β‐adrenergic receptor responsiveness, whereas reduced responsiveness to SNS in the ventricles may be primarily due to neurodegeneration. Abstract: The objective of this study was to determine how age‐related changes in sympathetic structure and function impact cardiac electrophysiology and intracellular Ca2+ handling. Innervated hearts from young (3‐4 months, YWT, n = 10) and aged (20‐24 months, AGED, n = 11) female mice (C57Bl6) were optically mapped using the voltage (Vm,)‐ and calcium (Ca2+)‐sensitive indicators Rh237 and Rhod2‐AM. Sympathetic nerve stimulation (SNS) was performed at the spinal cord (T1‐T3). β‐Adrenergic responsiveness was assessed with isoproterenol (1 μM, ISO). Sympathetic nerve density and noradrenaline content were also quantified. Stimulation thresholds necessary to produce a defined increase in heart rate (HR) with SNS were higher in AGED vs. YWT hearts (5.4 ± 0.4 vs. 3.8 ± 0.4 Hz, P < 0.05). Maximal HR with SNS was lower in AGED vs. YWT (20.5 ± 3.41% vs. 73.0 ± 7.63% increase, P < 0.05). β‐Adrenergic responsiveness of the atria (measured as percentage increase in HR with ISO) was decreased in AGED vs. YWT hearts (75.3 ± 22.5% vs. 148.5 ± 19.8%, P < 0.05). SNS significantly increased action potential duration (APD) in YWT but not AGED. Ca2+ transient durations and rise times were unchanged by SNS, yet AGED hearts had an increased susceptibility to Ca2+ alternans and ventricular arrhythmias. β‐Adrenergic responsiveness of all ventricular parameters were similar between AGED and YWT. Sympathetic nerve density and noradrenaline content were decreased in the AGED ventricle, but not atria, compared to YWT. These data suggest that decreased responsiveness to SNS in the aged atria may be primarily due to decreased β‐adrenergic responsiveness, whereas decreased responsiveness to SNS in the aged ventricles may be primarily due to nerve degeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
4. Decreased inward rectifying K+ current and increased ryanodine receptor sensitivity synergistically contribute to sustained focal arrhythmia in the intact rabbit heart.
- Author
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Myles, Rachel C., Wang, Lianguo, Bers, Donald M., and Ripplinger, Crystal M.
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HEART failure , *RYANODINE receptors , *ARRHYTHMIA , *CALCIUM channels , *VENTRICULAR tachycardia - Abstract
Key points Heart failure leads to dramatic electrophysiological remodelling as a result of numerous cellular and tissue-level changes. Important cellular changes include increased sensitivity of ryanodine receptors (RyRs) to Ca2+ release and down-regulation of the inward rectifying K+ current ( IK1), both of which contribute to triggered action potentials in isolated cells., We studied the role of increased RyR sensitivity and decreased IK1 in contributing to focal arrhythmia in the intact non-failing rabbit heart using optical mapping and pharmacological manipulation of RyRs and IK1., Neither increased RyR sensitivity or decreased IK1 alone led to significant increases in arrhythmia following local sympathetic stimulation; however, in combination, these two factors led to a significant increase in premature ventricular complexes and focal ventricular tachycardia., These results suggest synergism between increased RyR sensitivity and decreased IK1 in contributing to focal arrhythmia in the intact heart and may provide important insights into novel anti-arrhythmic treatments in heart failure., Abstract Heart failure (HF) results in dramatic electrophysiological remodelling, including increased sensitivity of ryanodine receptors (RyRs) and decreased inward rectifying K+ current ( IK1), which predisposes HF myocytes to delayed afterdepolarizations and triggered activity. Therefore, we sought to determine the role of increased RyR sensitivity and decreased IK1 in contributing to focal arrhythmia in the intact non-failing heart. Optical mapping of transmembrane potential and intracellular Ca2+ was performed in Langendorff-perfused rabbit hearts ( n = 15). Local β-adrenergic receptor stimulation with noradrenaline (norepinephrine; NA, 50 μl, 250 μ m) was applied to elicit focal activity (premature ventricular complexes (PVCs) or ventricular tachycardia (VT ≥ 3 beats)). NA was administered under control conditions (CTL) and following pretreatment with 50 μ m BaCl2 to reduce IK1, or 200 μ m caffeine (Caff) to sensitize RyRs, both alone and in combination. Local NA injection resulted in Ca2+-driven PVCs arising from the injection site in all hearts studied. No increase in NA-mediated PVCs was observed following pretreatment with either BaCl2 or Caff alone (CTL: 1.1 ± 0.7, BaCl2: 1.0 ± 0.7, Caff: 1.3 ± 0.8 PVCs/injection, P not significant). However, pretreatment with the combination of BaCl2 + Caff resulted in a significant increase in PVCs (2.3 ± 2.8 PVCs/injection, P < 0.05 vs. CTL, BaCl2, Caff). Additionally, pretreatment with BaCl2 + Caff led to sustained monomorphic VT arising from the NA application site in all hearts studied, which lasted up to 6 min following a single NA injection. VT was never observed under any other condition suggesting synergism between increased RyR sensitivity and decreased IK1 in contributing to focal activity. These findings may have important implications for the understanding and prevention of focal arrhythmia in HF. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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