Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension.

Right ventricular (RV) function is an important prognostic indicator for pulmonary arterial hypertension (PAH), a vasculopathy that primarily and disproportionally affects women with distinct pre- and postmenopausal clinical outcomes. However, most animal studies have overlooked the impact of sex and ovarian hormones on RV remodeling in PAH. Here, we combined invasive measurements of RV hemodynamics and morphology with computational models of RV biomechanics in sugen-hypoxia (SuHx)-treated male, ovary-intact female, and ovariectomized female rats.

Three-dimensional transistor arrays for intra- and inter-cellular recording.

Electrical impulse generation and its conduction within cells or cellular networks are the cornerstone of electrophysiology. However, the advancement of the field is limited by sensing accuracy and the scalability of current recording technologies. Here we describe a scalable platform that enables accurate recording of transmembrane potentials in electrogenic cells.

Cardiac cell type-specific gene regulatory programs and disease risk association.

Misregulated gene expression in human hearts can result in cardiovascular diseases that are leading causes of mortality worldwide. However, the limited information on the genomic location of candidate cis-regulatory elements (cCREs) such as enhancers and promoters in distinct cardiac cell types has restricted the understanding of these diseases. Here, we defined >287,000 cCREs in the four chambers of the human heart at single-cell resolution, which revealed cCREs and candidate transcription factors associated with cardiac cell types in a region-dependent manner and during heart failure.

Inducibility of abnormal automaticity and triggered activity in myocardial sleeves of canine pulmonary veins.

Background: To study the cellular mechanisms governing cardiac atrial arrhythmias initiated by ectopic focus (or foci) from pulmonary veins (PVs).

Methods: In the present in vitro study, we applied the conventional microelectrode technique to record intracellular action potentials in PV sleeves from dogs.

Results: In 80 normal healthy dogs, all action potentials recorded in cardiomyocytes from PV sleeves were fast-response.

Inhibition of L-type Ca(2+) current in Guinea pig ventricular myocytes by cisapride.

The effect of cisapride on L-type Ca(2+) current (I(Ca,L)) was studied in guinea pig ventricular myocytes using a whole-cell voltage-clamp technique and a conventional action potential recording method. Myocytes were held at -40 mV, and internally dialyzed and externally perfused with Na(+)- and K(+)-free solutions; cisapride elicited a concentration-dependent block of peak I(Ca,L), with a half-maximum inhibition concentration (IC(50)) of 46.9 microM.

Swelling-activated chloride current is activated in guinea pig cardiomyocytes from endotoxic shock.

Objective: Myocardial swelling occurs during endotoxic shock. The hypothesis that swelling-activated Cl- current (ICl,swell) activates during endotoxic shock was tested.

Methods: Endotoxic shock was induced by intravenous lipopolysaccharides (10 mg/kg) in guinea pigs.

Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves: a contradictory report.

Pulmonary veins may serve as source of ectopic focus (or foci) in initiating atrial tachyarrhythmias in human beings. However, the animal model for such focal atrial fibrillation is still lacking and cellular mechanism for arrhythmias remains to be studied. Recently, a series of reports of cellular electrophysiological characterization of pulmonary vein sleeves demonstrated an extremely high incidence of automaticity (varied from 40 to 76%) and triggered activity (from 0 to 44%) in normal healthy control dogs and rabbits.

Genistein and tyrphostin AG 556 block the action potential shortening in septic shock.

Background: We have previously shown that an increase in NO activity activated ATP-sensitive potassium channel (K(ATP)) and shortened action potential duration (APD) in an endotoxic shock model. Because the increase in NO production and the decrease of APD appear to be downstream late events in endotoxic shock, we hypothesized that a common signaling pathway might mediate these effects.

Methods: Using a guinea pig model of endotoxic shock, we investigated the effect of genistein and tyrphostin AG 556 on the cardiac action potential.

Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes.

Genistein is an isoflavone with potent inhibitory activity on protein tyrosine kinase. Previous studies have shown that genistein has additional effects, among which the direct blocking effects on various ionic channels have recently been disclosed. Using whole-cell voltage clamp and current clamp techniques, we demonstrate that micromolar concentrations of genistein dose-dependently and reversibly inhibit the inward rectifying K(+) current, and depolarize the resting membrane potential, resulting in abnormal automaticity in guinea pig ventricular myocytes.

Effects of sildenafil on cardiac repolarization.

Objectives: Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization.

Methods: We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs.