Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade.

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K(+) currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K(+) currents (I(TO), I(KSUS) and I(K1)) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique.

Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion.

Background And Purpose: Cannabidiol (CBD) is a phytocannabinoid, with anti-apoptotic, anti-inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis.

Experimental Approach: Male Sprague-Dawley rats received either vehicle or CBD (10 or 50 microg kg(-1) i.

A web-based tool for teaching pharmacy practice competency.

Objective: To implement and assess the effectiveness of the Strathclyde Computerized Randomized Interactive Prescription Tutor (SCRIPT) in teaching a competency-based undergraduate pharmacy course.

Design: Data on students' access to SCRIPT, collected by quantitative electronic data capture, were analyzed to determine student usage patterns and correlations between usage and grades in class assessments. Data on students' perceptions were collected by electronic questionnaire and semi-structured interviews.

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF.

Background: Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear.

Objective: This study sought to investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes that could predispose to AF.

Methods: Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery.

Cellular bases for human atrial fibrillation.

Atrial fibrillation (AF) causes substantial morbidity and mortality. It may be triggered and sustained by either reentrant or nonreentrant electrical activity. Human atrial cellular refractory period is shortened in chronic AF, likely aiding reentry.

Targeting sphingosine-1-phosphate signalling for cardioprotection.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid generated by the sphingosine kinase (SK1 or SK2)-catalysed phosphorylation of sphingosine. Plasma S1P is carried in high-density lipoprotein (HDL) or bound to albumin and is reported to arise from activated platelets and erythrocytes. In addition, extracellular SK1 released from vascular endothelial cells may also contribute to plasma S1P levels.

IP(3)R-mediated Ca(2+) release is modulated by anandamide in isolated cardiac nuclei.

Cannabinoids (CBs) are known to alter coronary vascular tone and cardiac performance. They also exhibit cardioprotective properties, particularly in their ability to limit the damage produced by ischaemia reperfusion injury. The mechanisms underlying these effects are unknown.

Post-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology.

Introduction: We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling.

Methods And Results: Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique.

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation.

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT(4) receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca(2+) current (I(CaL)), action potential duration (APD) and arrhythmic activity at 37 degrees C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10microM) produced an increase in I(CaL) of 115+/-21% above control (n=10 cells, 6 patients) that was significantly smaller than that in the SR group (232+/-33%; p<0.

Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats.

1. The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite. 2.

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic.

Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca(2+) current (I(CaL)) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm.

Endothelin and the ischaemic heart.

Soon after its identification as a powerful vasoconstrictor peptide, endothelin (ET-1) was implicated as a detrimental agent involved in determining the outcome of myocardial ischaemia and reperfusion. Early experimental studies demonstrated that ET(A) selective and mixed ET(A)/ET(B) receptor antagonists can reduce infarct size and prevent ischaemia-induced ventricular arrhythmias in models of ischaemia/reperfusion, implying that ET-1 acts through the ET(A) receptor to contribute to injury and arrhythmogenesis. However, as our understanding of the physiology of ET-1 has expanded, the role of ET-1 in the ischaemic heart appears ever more complex.

Electrophysiological and haemodynamic effects of endothelin ETA and ETB receptors in normal and ischaemic working rabbit hearts.

The aims of this study were to determine if endothelin-1 (ET-1) under normal and ischaemic conditions exhibits a direct arrhythmogenic effect that is independent of its ability to cause coronary vasoconstriction, and to determine the contribution of the ET(A) and ET(B) receptor subtype. ET(A/B) (with ET-1) and ET(A) (ET-1 in the presence of BQ-788) receptor activation resulted in a significant reduction in both epi- and endocardial monophasic action potential duration (MAPD(90)). ET(A) receptor activation reduced both epi- and endocardial effective refractory period (ERP).

Electrophysiological effects of prucalopride, a novel enterokinetic agent, on isolated atrial myocytes from patients treated with beta-adrenoceptor antagonists.

Prucalopride is a selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist developed for the treatment of gastrointestinal disorders. The endogenous agonist 5-HT acting via 5-HT4 receptors increases the L-type Ca2+ current (I(CaL)) with potentially proarrhythmic consequences (Pau et al., 2003).

Sarafotoxin 6c (S6c) reduces infarct size and preserves mRNA for the ETB receptor in the ischemic/reperfused myocardium of anesthetized rats.

The aims of this study were to determine if the ETB receptor agonist, sarafotoxin 6c (S6c) reduces myocardial infarct size following myocardial ischemia and reperfusion and to investigate whether any changes in mRNA for endothelin receptors in the injured myocardium were modified by S6c pretreatment. Hypnorm/Hypnovel anesthetized rats were subjected to occlusion of the left main coronary artery for 30 minutes, followed by 120 minutes reperfusion. Animals were administered a bolus dose of S6c (0.

Electrophysiological effects of 5-hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic beta-adrenoceptor blockade.

5-Hydroxytryptamine (5-HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5-HT4 receptors. The aims of this study were to examine the effects of 5-HT on the L-type Ca2+ current (ICaL) action potential duration (APD), the effective refractory period (ERP) and arrhythmic activity in human atrial cells, and to assess the effects of prior treatment with beta-adrenoceptor antagonists. Isolated myocytes, from the right atrial appendage of 27 consenting patients undergoing cardiac surgery who were in sinus rhythm, were studied using the whole-cell perforated patch-clamp technique at 37 degrees C.

Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation.

Objective: To assess the contribution of the Na, K pump current (I(p)) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether I(p) contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF).

Methods: Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (>3 months).

Results: In cells from patients in SR, the I(p) blocker, ouabain (10 microM) significantly depolarised the membrane potential, V(m), from -80+/-2 (mean+/-S.

Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling.

Objective: Chronic beta-adrenoceptor antagonist (beta-blocker) treatment reduces the incidence of reversion to AF in patients, possibly via an adaptive myocardial response. However, the underlying electrophysiological mechanisms are presently unclear. We aimed to investigate electrophysiological changes in human atrial cells associated with chronic treatment with beta-blockers and other cardiovascular-acting drugs.

Apex-to-base dispersion of refractoriness underlies the proarrhythmic effect of hypokalaemia/hypomagnesaemia in the rabbit heart.

Apex-to-base differences in the density of potassium currents have been recently described in isolated rabbit myocytes. The significance of those findings for arrhythmogenesis in the whole heart is not known. We aimed to examine electrophysiological effects of hypokalaemia/hypomagnesaemia in isolated working rabbit hearts.