Statins reduce short- and long-term mortality associated with postoperative atrial fibrillation after coronary artery bypass grafting: impact of postoperative atrial fibrillation and statin therapy on survival.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass grafting (CABG) surgery. The objective of this study was to determine the impact of POAF on both short- and long-term mortality following isolated CABG.

Hypothesis: POAF is associated with a poorer short and long-term mortality following CABG.

Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals.

QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile.

QRS widening and QT prolongation are associated with bupropion. The objectives were to elucidate its cardiac electrophysiological properties. Patch-clamp technique was used to assess the I(Kr) -, I(Ks) -, and I(Na) -blocking effects of bupropion.

Middle-aged men with increased waist circumference and elevated C-reactive protein level are at higher risk for postoperative atrial fibrillation following coronary artery bypass grafting surgery.

Introduction: We recently demonstrated that metabolic syndrome (MetS) is an independent risk factor for postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG). In the present work, we sought to determine which feature of the MetS is associated with POAF.

Methods And Results: We retrospectively analysed the association between metabolic features and the incidence of new-onset POAF in a total of 2214 male patients <65 years who underwent first isolated CABG.

A pilot study to estimate the feasibility of assessing the relationships between polymorphisms in hKv1.5 and atrial fibrillation in patients following coronary artery bypass graft surgery.

Background: Postoperative atrial fibrillation (AF) is a frequent complication following cardiac surgery. Risk factors leading to the development of postoperative AF are not well known and may be influenced by mutations of specific channels involved in atrial repolarization. Recently, the authors have identified three single nucleotide polymorphisms (SNPs) (R87Q, A251T and P307S) in the voltage-gated potassium channel hKv1.

Ischemic, genetic and pharmacological origins of cardiac arrhythmias: the contribution of the Quebec Heart Institute.

Research in the field of basic electrophysiology at the Quebec Heart Institute (Laval Hospital, Quebec City, Quebec) has evolved since its beginning in the 1990s. Interests were focused on cardiac arrhythmias induced by drugs, allelic variants and metabolic factors produced during ischemia. The results have contributed to the creation of new standards in drug development, more specifically, testing all new drugs for their potential effects on cardiac potassium currents, which could produce life-threatening proarrhythmic effects.

Reduced incidence of vagally induced atrial fibrillation and expression levels of connexins by n-3 polyunsaturated fatty acids in dogs.

Objectives: This open-label canine study assessed whether n-3 polyunsaturated fatty acids (PUFAs) prevent vagally induced atrial fibrillation (AF) and influence atrial tissue expression levels of connexins (CXs).

Background: n-3 polyunsaturated fatty acids in fish oils protect against sudden cardiac death and reduce postoperative AF. Changes in spatial organization of gap junctions or cellular CX levels have been linked to arrhythmogenesis.

Obesity and metabolic syndrome are independent risk factors for atrial fibrillation after coronary artery bypass graft surgery.

Background: Postoperative atrial fibrillation (POAF) is a highly prevalent complication after cardiac surgery with substantial effects on outcomes. Previous studies have reported that obesity is a risk factor for POAF after cardiac surgery. However, it is unknown whether the metabolic syndrome (MS) also increases the risk of postoperative atrial fibrillation.

Dimethyphenylpiperazinium, a nicotinic receptor agonist, downregulates inflammation in monocytes/macrophages through PI3K and PLC chronic activation.

Activation of nicotinic acetylcholine receptors (nAChRs) on inflammatory cells induces anti-inflammatory effects. The intracellular mechanisms that regulate this effect are still poorly understood. In neuronal cells, nAChRs are associated with phosphatidylinositol 3-kinase (PI3K).

New epilepsy seizure at high altitude without signs of acute mountain sickness or high altitude cerebral edema.

Neurological disturbances may be present at high altitude independently of high altitude cerebral edema. We report here the case of a patient who experienced for the first time generalized seizures after spending a night at an altitude of 5200 m, with no preceding symptoms of acute mountain sickness. An initial CT scan performed 12 hours after his loss of consciousness and an MRI scan performed 2 months later were normal.

Electrophysiological characterization of three non-synonymous single nucleotide polymorphisms (R87Q, A251T, and P307S) found in hKv1.5.

Non-synonymous single nucleotide polymorphisms (SNPs) in the KCNA5/hKv1.5 gene, which encodes for a voltage-gated K+ channel responsible for the I (Kur) current in the human atria, have been recently reported. To gain further knowledge on potential influence of hKv1.

Cut-off phenomenon in the protective effect of alcohols against lysophosphatidylcholine-induced calcium overload.

We studied the effect of chain length on the protective effect of alcohols against lysophosphatidylcholine (LPC)-induced Ca2+ overload in neonatal rat cardiomyocytes. We previously found that ethanol retards Ca2+ elevation. Cells were loaded with the Ca2+-sensitive fluorophore fura-2, and changes in fluorescence were followed.

Hydrogen peroxide modulates the Kv1.5 channel expressed in a mammalian cell line.

Reactive oxygen species have been implicated in different types of cardiac arrhythmias including human atrial fibrillation. Kv1.5, the presumed molecular correlate of I(Kur), is an important determinant of human atrial repolarization.

Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms.

Biophysical characteristics of a new mutation on the KCNQ1 potassium channel (L251P) causing long QT syndrome.

The congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by prolonged ventricular repolarization, syncope, and sudden death. Mutations causing LQTS have been identified in various genes that encode for ionic channels or their regulatory subunits. Several of these mutations have been reported on the KCNQ1 gene encoding for a potassium channel or its regulatory subunit (KCNE1).

Ethanol protects against lysophosphatidylcholine-induced uncoupling of cardiac cell pairs.

Moderate alcohol consumption is related to a reduction in cardiovascular deaths. Lysophosphatidylcholine (LPC) produces arrhythmias similar to those induced by ischemia most likely due to its uncoupling properties. We assessed effects of LPC in the presence of ethanol in cardiac myocyte pairs using the double whole-cell voltage-clamp technique.

Ethanol delays and reverses lysophosphatidylcholine-induced calcium overload in neonatal rat heart cells.

Increased lysophosphatidylcholine (LPC) production by the ischemic heart is associated with tissue damage. In vitro, LPC produces an increase in cytosolic [Ca2+], usually followed by cell contracture and lysis. Since ethanol reportedly protect cells during ischemia-reperfusion, we wished to determine whether ethanol could protect heart cells against LPC-induced Ca2+ overload.

Pimozide (Orap) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current in native cardiac myocytes.

Background: Several cases of QT prolongation and ventricular tachyarrhythmia have been reported with pimozide, a potent neuroleptic useful in the management of motor and phonic tics associated with Tourette syndrome. To further elucidate the mechanism underlying these clinical observations, the effects of pimozide on monophasic action potential duration (MAPD(90)) and on potassium currents involved in the repolarization of native isolated ventricular myocytes were examined.

Methods And Results: Studies were undertaken in eight isolated guinea pig hearts that demonstrated reverse rate-dependent prolongation of cardiac repolarization by pimozide 100 nmol/L.

Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx43 protein levels and gap junction distribution.

In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts.

Hydrogen peroxide modifies the kinetics of HERG channel expressed in a mammalian cell line.

Reactive oxygen species such as H2O2 were shown to influence both electrical and contractile properties of the heart. H2O2 modulates action potential duration and leads to reperfusion-induced arrhythmias. As these effects could involve the modulation of repolarizing currents, we assessed effects of H2O2 on HERG (which encodes the cardiac potassium channel I(Kr)) expressed in Chinese hamster ovary cells.

Vitamin K modulates cardiac action potential by blocking sodium and potassium ion channels.

Background: Cardiovascular collapses, syncopes, and sudden deaths have been observed following the rapid administration of intravenous vitamin K. Our objectives were to characterize the effects of vitamin K on cardiac action potentials and to evaluate effects of vitamin K on sodium and potassium currents, namely I(Na), I(Kr), and I(Ks).

Methods And Results: Guinea pig hearts (n = 21) were paced at a cycle length of 250 msec and exposed to vitamin K at 1.

Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders.

Background: Several cases of QT prolongation and ventricular tachyarrhythmia have been reported with domperidone, a gastrokinetic and antiemetic agent available worldwide but still under investigation in the United States. Although electrolyte disturbances such as hypokalemia could account for some of these events, we hypothesized that domperidone may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia.

Methods And Results: Studies were undertaken in 9 isolated guinea pig hearts, which demonstrated reverse use-dependent prolongation of cardiac repolarization by 100 nmol/L domperidone.

Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L.

Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes.

Venlafaxine is a newly introduced antidepressant agent. The drug causes selective inhibition of neuronal reuptake of serotonine and norepinephrine with little effect on other neurotransmitter systems. Cases of seizures, tachycardia, and QRS prolongation have been observed following drug overdose in humans.