Abstract:
:Torsades de pointes is the most typical ventricular tachycardia involving QT-interval prolongation. It is a rather unusual but potentially lethal ventricular tachycardia with a distinctive morphology favored by bradycardia, antiarrhythmic drugs and hypokalemia and requires specific treatment. Torsades de pointes has been shown to be related to bradycardia-dependent early afterdepolarizations (EAD) and/or increased dispersion of repolarization. However, although EAD can be obtained relatively easily in vitro with quinidine or sotalol, torsades de pointes are very difficult to reproduce in animal models. The models of torsades de pointes which have been proposed can be categorized as morphological, EAD-related or pharmacological models. The purpose of the 'morphological' models was to reproduce the twisting of QRS axis typical of torsades de pointes, with no consideration of other aspects such as long QT or bradycardia. These models were produced by epicardial electrical or chemical (aconitine) stimulation at two distant ventricular sites or by overdosing of quinidine in dogs with acute myocardial infarction. The second type of model focused on the conditions producing EAD in vitro. Ventricular tachycardias were obtained in anesthetized dogs using toxics such as cesium or anthopleurine, both producing EAD in vitro. These ventricular tachycardias were shown to be sensitive to magnesium, heart rate and autonomic tone, but torsades de pointes remained rare, at least after cesium injections. The pharmacological models that could be used to study the QT-dependent proarrhythmic effects of drugs are the anesthetized rabbit with alpha-adrenergic stimulation, and the conscious dog model with chronic AV-block and diuretic-induced hypokalemia. Methoxamine-treated anesthetized rabbits develop ventricular tachycardias during clofilium infusions. These ventricular tachycardias, although appearing at very high heart rates, have typical torsades de pointes aspects and are often associated with giant QT waves. The specificity of the model remains to be tested. In our conscious bradycardic and hypokalemic dogs, quinidine and sotalol but not flecainide, propranolol or lidocaine induced QT-dependent arrhythmogenic effects and torsades de pointes. Efficacy of high rate stimulations and magnesium were repeatedly observed. This demanding model, especially designed for qualitative drug comparisons, is also well suited to studies on the mechanisms of initiation of torsades de pointes. The pertinence of these models for estimating the risk of QT-dependent proarrhythmias associated with non-antiarrhythmic agents remains to be tested.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Weissenburger J,Davy JM,Chézalviel Fdoi
10.1111/j.1472-8206.1993.tb00215.xsubject
Has Abstractpub_date
1993-01-01 00:00:00pages
29-38issue
1eissn
0767-3981issn
1472-8206journal_volume
7pub_type
杂志文章,评审abstract::The new oral anticoagulants are announced as an important therapeutic revolution, particularly after their approval by authorities for stroke prevention in atrial fibrillation. However, the pharmacology of these new drugs is not homogeneous. In this review, we summarize the main pharmacological characteristics of the ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/fcp.12091
更新日期:2015-02-01 00:00:00
abstract::Thalidomide, a well-known immunomodulatory compound, has an anti-angiogenic activity, which may be utilized for the treatment of angiogenesis-related diseases such as hemangioendothelioma. The aim of the present study was to investigate both the antitumor role of thalidomide on hemangioendothelioma and the underlying ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12478
更新日期:2019-12-01 00:00:00
abstract::Cyclosporine A (CsA) is an immunosuppressor, which is most frequently used in the transplant surgery and in the treatment of autoimmune diseases. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA nephrotoxicity, hepatotoxicity and card...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2008.00609.x
更新日期:2008-08-01 00:00:00
abstract::The authors describe a case of valvular heart disease in a 48-year-old woman receiving benfluorex (150 mg t.i.d. for 8 years) and leading to surgical mitral valve replacement. Examination showed severe dyspnea with severe mitral regurgitation associated with tricuspid regurgitation. No other common disease known to af...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2006.00441.x
更新日期:2006-12-01 00:00:00
abstract::The fact that a considerable amount of clinical conditions suffering from ischemia-reperfusion injury (IRI) occur under general anesthesia has triggered researchers to focus on the effects of anesthetic drugs on IRI. Hence, the aim of this study was to compare the use of different anesthetic drugs in a skeletal IRI mo...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2009.00748.x
更新日期:2010-04-01 00:00:00
abstract::The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking t...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2006.00412.x
更新日期:2006-08-01 00:00:00
abstract::Angiotensin II AT1 receptor blockade (AT1-) has been shown to prolong survival in post-myocardial infarction (MI) heart failure in rats. In this study, we investigated whether an early AT1-induced improvement in coronary vasodilatation reserve (CVR) might be involved in this beneficial effect. Wistar rats with MI were...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1999.tb00374.x
更新日期:1999-01-01 00:00:00
abstract::The effect known as the GTP-shift refers to the complete conversion of receptors from the high- to the low agonist-affinity state in the presence of an excess of GTP or one of its analogs. 5'-Guanylylimidodiphosphate (GppNHp) was able to fully suppress the high (-)-isoproterenol-affinity of beta-adrenoceptors (beta AR...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1999.tb00335.x
更新日期:1999-01-01 00:00:00
abstract::The aim of this analysis was to compare vasoreactive properties of internal thoracic arteries (ITA) grafts from diabetic (DM) to those of non-diabetic (ND) patients. Ring segments of ITA, taken from patients undergoing coronary artery bypass grafting, were suspended in organ bath chambers filled with modified Krebs-He...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2009.00707.x
更新日期:2009-10-01 00:00:00
abstract::It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short-acting beta-1-adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1472-8206.2005.00351.x
更新日期:2005-10-01 00:00:00
abstract::The main of the present study was to determine the experimental conditions for an animal model of orthostatic hypotension based on tilting in rats. Blood pressure, heart rate and plasma catecholamine levels were measured before and after tilting in conscious and anaesthetized rats either breathing spontaneously or mec...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1992.tb00092.x
更新日期:1992-01-01 00:00:00
abstract::The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent s...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12038
更新日期:2014-06-01 00:00:00
abstract::The aim of our study was to analyse the protective effects of different alpha-tocopherol analogues 1) against fibrillations induced by an ischemia-reperfusion sequence, and 2) to further investigate in vitro the radical scavenging properties of these analogues by two sensitive methods. Concerning 1: isolated rat heart...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1998.tb00937.x
更新日期:1998-01-01 00:00:00
abstract::The blood-brain barrier (BBB) is responsible for the control of solutes' concentration in the brain. Tight junctions and multiple ATP-binding cassette (ABC) and SoLute Carrier (SLC) efflux transporters protect brain cells from xenobiotics, therefore reducing brain exposure to intentionally administered drugs. In epile...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12175
更新日期:2016-04-01 00:00:00
abstract::Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation or apoptosis. Microparticles from monocytes have been implicated in atherosclerosis and vascular inflammation, but their direct effects on endothelial cells are not completely elucidated. The present s...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2010.00898.x
更新日期:2011-12-01 00:00:00
abstract::The aim of this study was to investigate the mechanism of Na+ , K+ -ATPase (NKA) involved in low concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride staining and neurological deficit scores were performed to evaluate rat...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12652
更新日期:2021-01-22 00:00:00
abstract::During ischemia, large amounts of catecholamine are released to the myocardium from the sympathetic nerve endings in the heart. It has not been clearly shown whether the released catecholamine has detrimental or beneficial effects on postischemic myocardial contractile function. The aim of the present study was to inv...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1472-8206.2001.00015.x
更新日期:2001-04-01 00:00:00
abstract::Endocannabinoid system has attracted the researchers to investigate into its ever fascinating roles governing many of the physiological functions in the human body. The prime endogenous cannabinoids are arachidonoylethanolamide also called anandamide and 2-arachidonoylglycerol. Recent pharmacological advances point ou...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2006.00454.x
更新日期:2007-02-01 00:00:00
abstract::The aim of phase I studies per se is to explore the tolerance of new compounds which have demonstrated a certain level of activity in animals at sufficiently low non-toxic doses. In most cases, these studies are conducted in 2 steps in a limited number of healthy male volunteers: a single rising dose study followed by...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1990.tb00064.x
更新日期:1990-01-01 00:00:00
abstract::Oxidized low density lipoprotein (ox-LDL) and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) have been implicated in the development of atherosclerosis. This study was designed to investigate the expression regulation of LOX-1 by ox-LDL and the potential underlying mechanisms in cultured rat vascular ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2010.00885.x
更新日期:2011-10-01 00:00:00
abstract::The effects of Ketotifen and disodium cromoglycate were investigated on human and rabbit platelet activation. Ketotifen inhibited dose-dependently human and rabbit platelet aggregation. The paf-acether pathway was the most markedly influenced by Ketotifen in human and rabbit platelets (IC50 = 38.8 +/- 7.7 microM and 7...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1990.tb01011.x
更新日期:1990-01-01 00:00:00
abstract::Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclus...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2010.00865.x
更新日期:2011-08-01 00:00:00
abstract::In France, prescription of narcotics must be written on a tamper-resistant prescription form with specific technical particularities. Dosage and daily dose of medicines shall be written out entirely in letters. These prescription forms are also mandatory for buprenorphine, clorazepate, clonazepam, tianeptine, buccal m...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/fcp.12368
更新日期:2018-10-01 00:00:00
abstract::Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothe...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2012.01046.x
更新日期:2013-10-01 00:00:00
abstract::Beraprost sodium (BPS), an orally active PGI2 (prostaglandine 12) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co-prescribed with oral anticoagulants, we investigated its int...
journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1472-8206.2000.tb00021.x
更新日期:2000-05-01 00:00:00
abstract::The aim of the present study was the investigation of pretreatment effects with clonidine (0.06 mg/kg, intraperitoneal [i.p.]), lithium (1 mEq, i.p.) or quinine (0.5 mg/kg, i.p.) on the activities of various drugs acting on noradrenergic and/or serotonergic systems in the mouse tail suspension test. Drugs used in the ...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1997.tb00199.x
更新日期:1997-01-01 00:00:00
abstract::Strong sero-epidemiologic, pathologic, and experimental evidence suggests that Chlamydophila pneumoniae (Cpn) infection may play a causative role in the development of atherosclerosis. Cpn is an obligate intracellular gram-negative bacterium that is responsible for 10% of cases of community-acquired pneumonia. In addi...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.2010.00863.x
更新日期:2010-10-01 00:00:00
abstract::The effects of cooling (to 28 degrees C) and warming (to 41 degrees C) on the vasoconstrictions induced by 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and the role of nitric oxide in these effects were analyzed in human umbilical artery and vein. 5-HT (10(-9)-10(-4) M) and ACh (10(-9)-10(-4) M) induced concentr...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2007.00562.x
更新日期:2008-02-01 00:00:00
abstract::In the present study, contractile responses and [3H]-noradrenaline overflow evoked by electrical field stimulation were assessed, respectively, in the small mesenteric artery and in tail artery removed from rats pre-treated with either saline or lipopolysaccharide (LPS). In small mesenteric arteries, LPS treatment did...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.2000.tb00445.x
更新日期:2000-11-01 00:00:00
abstract::Many characters are genetically regulated as polymorphisms. This means that discrete groups are seen within the distribution of a certain character. Drug metabolism is no exception and the polymorphism of acetylation is recognised since the 50's. Polymorphic drug oxidation was discovered in the 70's and has been exten...
journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1472-8206.1991.tb00713.x
更新日期:1991-01-01 00:00:00