Role of NADPH oxidase and xanthine oxidase in mediating inducible VT/VF and triggered activity in a canine model of myocardial ischemia.

Background: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF.

Novel indices for left-ventricular dyssynchrony characterization based on highly automated segmentation from real-time 3-d echocardiography.

Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an invasive and expensive treatment option for left ventricular mechanical dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the unreliability of the current standard CRT indicators. Real-time three-dimensional (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time) information about the LV and is suitable for LVMD assessment.

Association among intracardiac T-wave alternans, ischemia, and spontaneous ventricular arrhythmias after coronary artery occlusion in a canine model.

T-wave alternans (TWA) has been investigated as a marker for susceptibility to lethal ventricular arrhythmia. In this article, we studied intracardiac TWA and ischemia as predictors of spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in a canine model of coronary artery occlusion (CAO). Anesthetized, open-chest dogs were studied.

Catecholamine-independent heart rate increases require Ca2+/calmodulin-dependent protein kinase II.

Background: Catecholamines increase heart rate by augmenting the cAMP-responsive hyperpolarization-activated cyclic nucleotide-gated channel 4 pacemaker current (I(f)) and by promoting inward Na(+)/Ca(2+) exchanger current (I(NCX)) by a "Ca(2+) clock" mechanism in sinoatrial nodal cells (SANCs). The importance, identity, and function of signals that connect I(f) and Ca(2+) clock mechanisms are uncertain and controversial, but the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for physiological heart rate responses to β-adrenergic receptor (β-AR) stimulation. The aim of this study was to measure the contribution of the Ca(2+) clock and CaMKII to cardiac pacing independent of β-AR agonist stimulation.

I(f) and SR Ca(2+) release both contribute to pacemaker activity in canine sinoatrial node cells.

Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a 'voltage clock' and a Ca(2+) dependent process, or 'Ca(2+) clock.' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (I(f)) is thought to be particularly important. A Ca(2+) dependent process triggers APs when sarcoplasmic reticulum (SR) Ca(2+) release activates inward current carried by the forward mode of the electrogenic Na(+)/Ca(2+) exchanger (NCX).

Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT(2) receptor.

Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT.

Free radical scavenger specifically prevents ischemic focal ventricular tachycardia.

Background: Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA), which may be blocked by scavenging reactive oxygen species (ROS).

Objective: This study analyzed effects of acutely administered ROS scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT in vivo and TA in vitro.

Methods: Forty-three alpha chloralose anesthetized dogs with coronary artery occlusion were studied.

Alpha-2 adrenergic antagonism enhances risk of ventricular tachycardia during acute ischemia.

Objective: In this study we tested the hypothesis that alpha-2 adrenergic antagonism could facilitate induction of previously non-inducible ventricular tachycardia (VT) during acute ischemia. Previous reports suggest that VT during ischemia may be modulated by (alpha-2 adrenergic agonists.

Design: The left anterior descending artery was occluded after instrumentation of the ischemic risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms.

Lovastatin specifically prevents focal ischemic ventricular tachycardia due to triggered activity.

Background: Use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor has been associated with reduced implantable defibrillator shocks in several multicenter trials, suggesting an antiarrhythmic effect.

Objective: The purpose of this study was to determine if lovastatin had an antiarrhythmic effect in a canine model of ischemic and inducible ventricular tachycardia (VT).

Methods: Forty-seven alpha-chloralose anesthetized dogs underwent left anterior descending coronary occlusion.

Percent right ventricular pacing predicts outcomes in the DAVID trial.

Background: The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group.

Objectives: The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial.

Overdrive pacing of early ischemic ventricular tachycardia: evidence for both reentry and triggered activity.

Entrainment can be a useful method to identify reentry as a mechanism of ventricular tachycardia (VT). In this study, we evaluated the effect of gradually decreasing cycle lengths of overdrive pacing for stable VT induced in a canine model 1-3 h after coronary occlusion. Intact dogs underwent anterior descending coronary artery occlusion after instrumentation of the risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms.

Pharmacological stimulation of cardiac gap junction coupling does not affect ischemia-induced focal ventricular tachycardia or triggered activity in dogs.

The role of gap junction intercellular communication (GJIC) in ischemia-induced focal ventricular tachycardia (VT) is unknown. We have developed a new, stable antiarrhythmic peptide analog named ZP123 that selectively increases GJIC and prevents reentrant VT. Our aim in this study was to use ZP123 as a tool to assess the role of GJIC on occurrence of ischemia-induced focal VT and triggered activity (TA) due to delayed afterdepolarizations (DADs).

Triggered activity due to delayed afterdepolarizations in sites of focal origin of ischemic ventricular tachycardia.

This study for the first time systematically evaluated the site of origin of focal ventricular tachycardia (VT) induced 1-3 h after acute coronary artery ligation in dogs. We determined whether delayed afterdepolarizations (DADs) and triggered activity (TA) are more often recorded from ischemic endocardium excised from focal sites of VT origin. A total of 145 alpha-chloralose-anesthetized dogs were studied: in 54 dogs without inducible VT, normal or ischemic endocardium was investigated in vitro; in 91 dogs, inducible VT was studied by three-dimensional activation mapping, with in vitro study of 51 endocardial foci compared with 40 endocardial ischemic sites not of VT origin.

Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression.

Depression is an important public health problem and is considered to be an independent risk factor for coronary artery disease. The pathophysiological mechanisms that link depression with adverse cardiovascular events (e.g.

Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

Introduction: The implantable cardioverter defibrillator (ICD) is commonly used to treat patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Arrhythmia recurrence rates in these patients are high, but which patients will receive a therapy and the forms of arrhythmia recurrence (VT or VF) are poorly understood.

Methods And Results: The therapy delivered by the ICD was examined in 449 patients randomized to ICD therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs.

Introduction: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion.

Methods And Results: Voltage clamp experiments demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion.

Alpha 2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo.

We previously reported that alpha(2)-adrenergic receptor (alpha(2)-AR) stimulation in Purkinje fibers in vitro prolongs action potential duration and suppresses beta-adrenergic-induced delayed afterdepolarizations and sustained triggered activities. We examined the effects of alpha(2)-AR stimulation on reperfusion-induced ventricular arrhythmias [ventricular tachycardia/ventricular fibrillation (VT/VF)] in vivo. Arterial blood pressure, heart rate, surface electrocardiogram, and renal sympathetic nerve activities were recorded simultaneously in Sprague-Dawley rats.

Purkinje involvement in arrhythmias after coronary artery reperfusion.

Previous studies have indicated that the endocardium may be responsible for a large portion of ventricular tachycardia (VT) seen with reperfusion of ischemic myocardium. To evaluate the role of the Purkinje system in nonreentrant VT arising from the endocardium after reperfusion, the anterior descending coronary artery was occluded for 20 min and then reperfused in 23 dogs after instrumentation of the risk zone with 21 multipolar plunge needles. VT with focal Purkinje origin was defined as a focal endocardial VT with Purkinje potentials recorded before the earliest endocardial myopotential.