Early left ventricular regional contractile impairment in chronic mitral regurgitation occurs in a consistent, heterogeneous pattern.

Objectives: The clinical guidelines for asymptomatic patients with chronic mitral regurgitation (MR) use the ejection fraction (EF) to trigger surgical referral. We hypothesized that the EF is not sensitive enough to detect the earliest contractile injury in chronic MR and that the injury associated with chronic MR is not global but heterogeneous, occurring regionally and predictably, before the onset of global left ventricular (LV) dysfunction.

Methods: Fifteen patients with chronic MR and normal LVEF by echocardiography underwent cardiac magnetic resonance imaging with tissue tagging.

Epicardial ablation performance of a novel radiofrequency device on the beating heart in pigs.

Purpose: Only bipolar clamps create reliable transmural lesions on the beating heart. This study evaluated the performance of a new radiofrequency (RF) device on the beating heart in an acute porcine model.

Description: Six domestic pigs were ablated with a novel bipolar RF linear device on the beating heart (ablation time of 40 s, 3 each on right and left atria and 1 each on superior and inferior vena cavae).

Heterogeneity and function of K(ATP) channels in canine hearts.

Background: The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent reports that SUR1 is predominant in mouse atrial K(ATP) channels.

Objective: To assess SUR subunit composition of K(ATP) channels and consequence of K(ATP) activation for action potential duration (APD) in dog hearts.

Impact of differential right-to-left shunting on systemic perfusion in pulmonary arterial hypertension.

Objectives: This study aimed at identifying the ideal right-to-left shunt-fraction to improve cardiac output (CO) and systemic perfusion in pulmonary arterial hypertension (PHT).

Background: Atrial septostomy (AS) has been a high-risk therapeutic option for symptomatic drug-refractory patients with PHT. Results have been unpredictable due to limited knowledge of the optimal shunt-quantity.

Differential impact of short periods of rapid atrial pacing on left and right atrial mechanical function.

Current techniques to describe atrial function are limited by their load dependency and hence do not accurately reflect intrinsic mechanical properties. To assess the impact of atrial fibrillation on atrial function, combined pressure-volume relationships (PVR) measured by conductance catheters were used to evaluate the right (RA) and left (LA) atrium in 12 isoflurane-anesthetized pigs. Biatrial PVR were recorded over a wide range of volumes during transient caval occlusion at baseline sinus rhythm (SR), after onset of rapid atrial pacing (RAP), after 1 h of RAP, after conversion to SR, and after 1 h of recovery.

Patch clamp and perfusion techniques for studying ion channels expressed in Xenopus oocytes.

The protocol presented here is designed to study the activation of the large conductance, voltage- and Ca(2+)-activated K(+) (BK) channels. The protocol may also be used to study the structure-function relationship for other ion channels and neurotransmitter receptors. BK channels are widely expressed in different tissues and have been implicated in many physiological functions, including regulation of smooth muscle contraction, frequency tuning of inner hair cells and regulation of neurotransmitter release.

Modulation of BK channel gating by the ß2 subunit involves both membrane-spanning and cytoplasmic domains of Slo1.

Large-conductance, Ca(2+)- and voltage-sensitive K(+) (BK) channels regulate neuronal functions such as spike frequency adaptation and transmitter release. BK channels are composed of four Slo1 subunits, which contain the voltage-sensing and pore-gate domains in the membrane and Ca(2+) binding sites in the cytoplasmic domain, and accessory β subunits. Four types of BK channel β subunits (β1-β4) show differential tissue distribution and unique functional modulation, resulting in diverse phenotypes of BK channels.

BK channel activation: structural and functional insights.

The voltage- and Ca(2+)-activated K(+) (BK) channels are involved in the regulation of neurotransmitter release and neuronal excitability. Structurally, BK channels are homologous to voltage- and ligand-gated K(+) channels, having a voltage sensor and pore as the membrane-spanning domain and a cytosolic domain containing metal binding sites. Recently published electron cryomicroscopy (cryo-EM) and X-ray crystallographic structures of the BK channel provided the first glimpse into the assembly of these domains, corroborating the close interactions among these domains during channel gating that have been suggested by functional studies.

{beta} subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia.

Large conductance Ca(2+)-activated K(+) (BK) channels modulate many physiological processes including neuronal excitability, synaptic transmission and regulation of myogenic tone. A gain-of-function (E/D) mutation in the pore-forming alpha subunit (Slo1) of the BK channel was recently identified and is linked to human neurological diseases of coexistent generalized epilepsy and paroxysmal dyskinesia. Here we performed macroscopic current recordings to examine the effects of the E/D mutation on the gating kinetics, and voltage and Ca(2+) dependence of the BK channel activation in the presence of four different beta subunits (beta1-4).

Subunit-specific effect of the voltage sensor domain on Ca2+ sensitivity of BK channels.

Large conductance Ca(2+)- and voltage-activated K(+) (BK) channels, composed of pore-forming alpha-subunits and auxiliary beta-subunits, play important roles in diverse physiological processes. The differences in BK channel phenotypes are primarily due to the tissue-specific expression of beta-subunits (beta1-beta4) that modulate channel function differently. Yet, the molecular basis of the subunit-specific regulation is not clear.