Background-Gap junction resistivity, R j , has been proposed as a key determinant of conduction velocity (CV). However, studies in connexin-gene knockout mice demonstrated significant CV slowing only with near-complete connexin deletion, and these findings led to the concept of a significant redundancy of myocardial gap junctions. We challenged this prevailing concept and addressed the hypothesis that there is a continuous relationship between R j and CV, each independently measured in human and guinea-pig myocardium. Methods and Results-R j and CV were directly measured by oil-gap impedance and microelectrode techniques in human left ventricular myocardium from patients with hypertrophic cardiomyopathy and in guinea-pig atrial and ventricular myocardium before and during pharmacological uncoupling with 20-µmol/L carbenoxolone. There was a continuous relationship between R j and CV in human and guinea-pig myocardium, pre-and post-carbenoxolone (r 2 =0.946; P<0.01). In guinea-pig left ventricle, left atrium, and right atrium, carbenoxolone increased R j by 28±9%, 26±16%, and 25±14% and slowed CV by 17±3%, 23±8%, and 11±4% respectively (all P<0.05 versus control). As a clinically accessible measure of local microscopic myocardial conduction slowing in vivo in the intact human heart, carbenoxolone prolonged electrogram duration in the right atrium (39.7±4.2 to 42.3±4.3 ms; P=0.01) and right ventricle (48.1±2.5 to 53.3±5.3 ms; P<0.01). Conclusions-There is a continuous relationship between R j and CV that is consistent between cardiac chambers and across species, indicating that naturally occurring variations in cellular coupling can account for variations in CV, and that the concept that there is massive redundancy of coupling is not tenable. (Circ Arrhythm Electrophysiol. 2013;6:1208-1214.)

Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

This manuscript describes initial applications of a unique new intravascular ultrasound imaging catheter. This 5.5F catheter uses an over-the-wire design and incorporates a phased array transducer at its tip. There are no moving parts. A 360 degree image is produced perpendicular to the catheter axis using a 20 MHz center frequency. A dedicated minicomputer is used for initial image processing, as well as enhancement and analysis. Initial studies using phantoms demonstrated excellent accuracy for linear dimensions (r = 0.99, range 3.0 to 7.6 mm, image = 1.0 phantom + 0.1). Serial imaging of the same arterial segment in vitro showed good reproducibility (coefficients of variance 2.5-5.2%). Likewise, intra- and inter-observer variability in image analysis was minimal (r = 0.92-0.99). Initial in vivo studies were performed in dogs. The catheter was easily passed over a wire into mesenteric, cerebral and coronary vessels without evidence of significant vessel trauma. Subsequently, 20 patients had percutaneous coronary imaging performed during cardiac catheterization. Cardiac motion was rarely a problem and acceptable images were obtained in all but two patients. Areas of calcification, mild stenoses, branching vessels and graft atherosclerosis could be identified. We conclude that intracoronary ultrasound imaging will be useful for assessing vascular pathology, for studying both rapid change in vessel size as well as chronic progression or regression of atherosclerosis, and for assisting with new therapeutic interventions.

Background-The relative roles of the gap-junctional proteins connexin40 (Cx40) and connexin43 (Cx43) in determining human atrial myocardial resistivity is unknown. In addressing the hypothesis that changing relative expression of Cx40 and Cx43 underlies an increase in human atrial myocardial resistivity with age, this relationship was investigated by direct ex vivo measurement of gap-junctional resistivity and quantitative connexin immunoblotting and immunohistochemistry. Methods and Results-Oil-gap impedance measurements were performed to determine resistivity of the intracellular pathway (R i ), which correlated with total Cx40 quantification by Western blotting (r s =0.64, P<0.01, n=20). Specific gapjunctional resistivity (R j ) correlated not only with Western immunoquantification of Cx40 (r s =0.63, P=0.01, n=20), but also more specifically, with the Cx40 fraction localized to the intercalated disks on immunohistochemical quantification (r s =0.66, P=0.02, n=12). Although Cx43 expression showed no correlation with resistivity values, the proportional expression of the 2 connexins, (Cx40/[Cx40+Cx43]) correlated with R i and R j (r s =0.58, P<0.01 for R i and r s =0.51, P=0.02 for R j ). Advancing age was associated with a rise in R i (r s =0.77, P<0.0001), R j (r s =0.65, P<0.001, n=23), Cx40 quantity (r s =0.54, P=0.01, n=20), and Cx40 gap-junction protein per unit area of en face disk (r s =0.61, P=0.02, n=12). Conclusions-Cx40 is associated with human right atrial gap-junctional resistivity such that increased total, gap-junctional, and proportional Cx40 expression increases gap-junctional resistivity. Accordingly, advancing age is associated with an increase in Cx40 expression and a corresponding increase in gap-junctional resistivity. These findings are the first to demonstrate this relationship and a mechanistic explanation for changing atrial conduction and age-related arrhythmic tendency. Patients and Methods Specimen Source, Collection, and HandlingThe use of human tissue conformed to the principles outlined in the Declaration of Helsinki, and the study had local Ethical Committee approval with written informed consent. Atrial appendage biopsies were collected from patients undergoing cardiac surgery at The London Chest Hospital, London, UK. Twenty-three patients (15 male) in sinus rhythm (age 68±8 years, range 53-80 years) undergoing coronary bypass surgery (n=15), aortic valve replacement (n=3), or both (n=5) were included. Patients were in sinus rhythm at the time of surgery as assessed by ECG and did not have any history of atrial arrhythmia. All patients underwent surgery using conventional cardiopulmonary bypass support, and biopsies were collected from the tips of the right atrial appendage immediately after the pericardium was opened and before exposure to cardioplegic agents. Samples were divided immediately on collection; one part was snap-frozen in liquid nitrogen at −70ºC for subsequent Cx quantification and immunolabeling, and the remainder was transported to the laboratory in preoxyge...