Microtubules and angiotensin II receptors contribute to modulation of repolarization induced by ventricular pacing.

Background: Left ventricular pacing (LVP) in canine heart alters ventricular activation, leading to reduced transient outward potassium current (I(to)), loss of the epicardial action potential notch, and T-wave vector displacement. These repolarization changes, referred to as cardiac memory, are initiated by locally increased angiotensin II (AngII) levels. In HEK293 cells in which Kv4.

Effect of skeletal muscle Na(+) channel delivered via a cell platform on cardiac conduction and arrhythmia induction.

Background: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na(+) channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1.

Angiotensin II increases corpus cavernosal contractility and oxidative stress in partial bladder outlet obstructed rabbits: relevance to erectile dysfunction.

Introduction: We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells.

Aim: To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO.

Methods: Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits.

SkM1 and Cx32 improve conduction in canine myocardial infarcts yet only SkM1 is antiarrhythmic.

Aims: Reentry accounts for most life-threatening arrhythmias, complicating myocardial infarction, and therapies that consistently prevent reentry from occurring are lacking. In this study, we compare antiarrhythmic effects of gene transfer of green fluorescent protein (GFP; sham), the skeletal muscle sodium channel (SkM1), the liver-specific connexin (Cx32), and SkM1/Cx32 in the subacute canine infarct.

Methods And Results: Immediately after ligation of the left anterior descending artery, viral constructs were implanted in the epicardial border zone (EBZ).

Implantation of sinoatrial node cells into canine right ventricle: biological pacing appears limited by the substrate.

Biological pacing has been proposed as a physiologic counterpart to electronic pacing, and the sinoatrial node (SAN) is the general standard for biological pacemakers. We tested the expression of SAN pacemaker cell activity when implanted autologously in the right ventricle (RV). We induced complete heart block and implanted electronic pacemakers in the RV of adult mongrel dogs.

Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal.

Background: Biological pacemakers based on the HCN2 channel isoform respond to beta-adrenergic and muscarinic stimulation, suggesting a capacity to respond to autonomic input.

Objective: The purpose of this study was to investigate autonomic response to emotional arousal in canines implanted with murine HCN2-based biological pacemakers using gene therapy.

Methods: An electronic pacemaker was implanted with its lead in the right ventricular apical endocardium (VVI 35 bpm).

Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.

Background: Skeletal muscle sodium channel (Nav1.4) expression in border zone myocardium increases action potential upstroke velocity in depolarized isolated tissue. Because resting membrane potential in the 1-week canine infarct is reduced, we hypothesized that conduction velocity (CV) is greater in Nav1.

Determinants of CREB degradation and KChIP2 gene transcription in cardiac memory.

Background: Left ventricular pacing (LVP) to induce cardiac memory (CM) in dogs results in a decreased transient outward K current (I(to)) and reduced mRNA and protein of the I(to) channel accessory subunit, KChIP2. The KChIP2 decrease is attributed to a decrease in its transcription factor, cyclic adenosine monophosphate response element binding protein (CREB).

Objective: This study sought to determine the mechanisms responsible for the CREB decrease that is initiated by LVP.

Epicardial border zone overexpression of skeletal muscle sodium channel SkM1 normalizes activation, preserves conduction, and suppresses ventricular arrhythmia: an in silico, in vivo, in vitro study.

Background: In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel (SCN5A) is largely inactivated, contributing to low action potential upstroke velocity (V(max)), slow conduction, and reentry. We hypothesized that a fast inward current such as the skeletal muscle sodium channel (SkM1) operating more effectively at depolarized membrane potentials might restore fast conduction in epicardial border zones and be antiarrhythmic.

Methods And Results: Computer simulations were done with a modified Hund-Rudy model.

The effect of vardenafil (a PDE type 5 inhibitor) on renal function in the diabetic rabbit: a pilot study.

Background: Diabetic nephropathy is a common cause of impaired renal function. We investigated the effect vardenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, has on renal function in the diabetic rabbit.

Materials And Methods: Blood was taken at 4 and 6 months from control and alloxan-induced diabetic animals (n=8, in each group) and biochemical variables pertaining to renal function determined.

Serotonin induces a biphasic response in rabbit cavernosal smooth muscle: relevance to the erectile process.

Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT.

Methods: Organ bath studies were used.

Gene therapy and erectile dysfunction: the current status.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e.

Doxazosin and serotonin (5-HT) receptor (1A, 2A, and 4) antagonists inhibit 5-HT-mediated human cavernosal contraction.

Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only a few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT in human erection.

Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum.

Background: Endothelin (ET-1) may play a role in the regulation of erection but this has not been conclusively demonstrated. Augmented cavernosal smooth muscle (CSM) contraction in the rat occurs following exposure to both ET-1 and phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the erectile process.

The management of phosphodiesterase-5 (PDE5) inhibitor failure.

The oral phosphodiesterase type 5 (PDE5) inhibitors have made a valuable contribution to the treatment of erectile dysfunction (ED). PDE5 inhibitors enhance cavernosal smooth muscle relaxation, vasodilatation and penile erection. However, PDE5 inhibitors are not always effective.

Erectile dysfunction: a need for greater awareness.

Research has led to effective treatment regimes for erectile dysfunction (ED). Convincing evidence links vascular risk factors (hypertension, diabetes mellitus, hyperlipidaemia and smoking) with ED. This association is not surprising since the corpus cavernosum is a modified vascular tissue.