Abstract:
:Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Jeevaratnam K,Chadda KR,Salvage SC,Valli H,Ahmad S,Grace AA,Huang CLdoi
10.1111/1440-1681.12721subject
Has Abstractpub_date
2017-12-01 00:00:00pages
38-45eissn
0305-1870issn
1440-1681journal_volume
44 Suppl 1pub_type
杂志文章,评审abstract::We compared the intraocular pressure (IOP)-lowering effect and safety profile of latanoprost (Xalatan) with its generic variant, Glautan (Unipharm, Tel Aviv, Israel). After 1 and 4 weeks of treatment, a randomized, prospective, cross-over comparison was carried out that included patients with open-angle glaucoma or oc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12329
更新日期:2015-02-01 00:00:00
abstract::1. It has been proposed that hypertension alters the respiratory and cardiovascular responses to chemoreceptor stimulation. However, in studies of human hypertension or in genetic animal models of hypertension it has been difficult to unequivocally attribute the changes to hypertension per se, rather than to a genetic...
journal_title:Clinical and experimental pharmacology & physiology
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02765.x
更新日期:1996-06-01 00:00:00
abstract::1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04830.x
更新日期:2008-01-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05593.x
更新日期:2011-11-01 00:00:00
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doi:10.1046/j.1440-1681.2002.03781.x
更新日期:2002-12-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00455.x
更新日期:1992-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/j.1440-1681.1996.tb02609.x
更新日期:1996-03-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00501.x
更新日期:1992-07-01 00:00:00
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更新日期:2009-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04336.x
更新日期:2006-01-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1440-1681.2001.03465.x
更新日期:2001-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1978.tb00708.x
更新日期:1978-09-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2011.05662.x
更新日期:2012-08-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2003.03920.x
更新日期:2003-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05029.x
更新日期:2009-01-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 更正并重新发布的文章,杂志文章
doi:
更新日期:1999-10-01 00:00:00
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doi:10.1111/j.1440-1681.1994.tb02486.x
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更新日期:2017-11-01 00:00:00
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更新日期:2015-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
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更新日期:2009-02-01 00:00:00
abstract::1. Levodopa markedly reduces parkinsonism during the first years of treatment. However, with continued therapy the response to levodopa becomes erratic and is complicated by involuntary movements. To improve the therapy of parkinsonism, the challenge is to understand why fluctuations in response develop and, once deve...
journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/j.1440-1681.1995.tb01946.x
更新日期:1995-11-01 00:00:00
abstract::1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associate...
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pub_type: 杂志文章
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更新日期:2007-11-01 00:00:00
abstract::1. The intravenous administration of nicergoline (5 mg) was followed by a rapid and sustained lowering of blood pressure; less rapid effects were bradycardia and an elevation of cardiac output. These delayed effects are consistent with an indirect action on the alpha-adrenoreceptors of the central nervous system. 2. F...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00051.x
更新日期:1980-03-01 00:00:00
abstract::1. It has previously been shown that perfusion with high O2-affinity-erythrocytes decreases venous PO2 (PVO2) and decreases O2 uptake (VO2) in contracting muscle at the same O2 delivery (arterial O2 concentration x flow). A linear VO2-PVO2 relationship has been obtained with a VO2-axis intercept, suggesting that, duri...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03100.x
更新日期:1999-08-01 00:00:00
abstract::1. Erlotinib, a small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, has been approved for the management of advanced non-small cell lung cancer. The aim of the present study was to investigate whether erlotinib exerts potent antitumour activities through the reactive oxygen species (RO...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
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更新日期:2009-05-01 00:00:00
abstract::The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were pe...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12392
更新日期:2015-06-01 00:00:00