Omnipolarity applied to equi-spaced electrode array for ventricular tachycardia substrate mapping

Aims : Bipolar electrogram (BiEGM)-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OTEGMs), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional BiEGMs on two orientations: along (AL) and across (AC) array splines. Methods and results: The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OTEGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OTEGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles (P < 0.05). Omnipolar EGM voltage maps were 37% denser than BiEGM maps. In addition, OTEGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than BiEGM by 39% and 47% over both infarcted and healthy areas, respectively (P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional BiEGMs from both orientations. Conclusion: An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.This work was funded by Abbott Laboratories, St. Paul, MN, USA.S

Application of intravenous electrocardiography for insertion of central veins dialysis catheters

One fifth of the inserted dialysis catheters in the internal jugular or subclavian veins may be misplaced. Appropriate positioning of the catheter tip is sometimes difficult. We attempted to use intravenous electrocardiography (ECG) to guide catheter tip positioning in 30 hemodialysis patients (17 (57&#x0025;) were men, and the mean age was 43 &#177; 12 years). who required vascular accesses for dialysis by insertion of double lumen temporary catheters via the jugular veins. Before cathe-terization, standard ECG on the long lead D II was performed and P-wave height was recorded. P-wave voltage was also measured via the blue (venous) and red (arterial) lumens, using the guide wire as an electrical conductor. After confirmation of the appropriate position of the catheter tip at the superior vena cava (SVC)-right atrial junction using chest radiography, the ECG lead corres-ponding to the right hand was connected to the guide wire lodged inside the lumen of the blue catheter. P-wave height in the long lead D II was recorded. The guide wire was withdrawn so as to bring its tip tangent to the tip of the red catheter. ECG was performed on the long lead D II in a similar manner, and the P-wave height was recorded. The mean P-wave voltage in normal ECG and intravenous ECG (red and blue catheter tips) measured 1.27 &#177; 0.38 mm, 3.10 &#177; 0.95 mm, and 5.42 &#177; 1.76 mm, respectively. The difference between the mean P-wave voltages measured in standard and intravenous ECG (blue and red catheter tips) was statistically significant (P&lt; 0.05). We conclude that the dialysis catheter tip can be positioned appropriately via the measurement of the P-wave height by intravenous ECG and using the sinoatrial node as an accurate landmark. This method can complement the chest radiography in the appropriate placement of the central vein catheters

GLP-1 receptor agonism ameliorates hepatic VLDL overproduction and de novo lipogenesis in insulin resistance

Background/objectives: Fasting dyslipidemia is commonly observed in insulin resistant states and mechanistically linked to hepatic overproduction of very low density lipoprotein (VLDL). Recently, the incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in ameliorating dyslipidemia associated with insulin resistance and reducing hepatic lipid stores. Given that hepatic VLDL production is a key determinant of circulating lipid levels, we investigated the role of both peripheral and central GLP-1 receptor (GLP-1R) agonism in regulation of VLDL production. Methods: The fructose-fed Syrian golden hamster was employed as a model of diet-induced insulin resistance and VLDL overproduction. Hamsters were treated with the GLP-1R agonist exendin-4 by intraperitoneal (ip) injection for peripheral studies or by intracerebroventricular (ICV) administration into the 3rd ventricle for central studies. Peripheral studies were repeated in vagotomised hamsters. Results: Short term (7–10 day) peripheral exendin-4 enhanced satiety and also prevented fructose-induced fasting dyslipidemia and hyperinsulinemia. These changes were accompanied by decreased fasting plasma glucose levels, reduced hepatic lipid content and decreased levels of VLDL-TG and -apoB100 in plasma. The observed changes in fasting dyslipidemia could be partially explained by reduced respiratory exchange ratio (RER) thereby indicating a switch in energy utilization from carbohydrate to lipid. Additionally, exendin-4 reduced mRNA markers associated with hepatic de novo lipogenesis and inflammation. Despite these observations, GLP-1R activity could not be detected in primary hamster hepatocytes, thus leading to the investigation of a potential brain–liver axis functioning to regulate lipid metabolism. Short term (4 day) central administration of exendin-4 decreased body weight and food consumption and further prevented fructose-induced hypertriglyceridemia. Additionally, the peripheral lipid-lowering effects of exendin-4 were negated in vagotomised hamsters implicating the involvement of parasympathetic signaling. Conclusion: Exendin-4 prevents fructose-induced dyslipidemia and hepatic VLDL overproduction in insulin resistance through an indirect mechanism involving altered energy utilization, decreased hepatic lipid synthesis and also requires an intact parasympathetic signaling pathway

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias

Summary: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation. : In this article, Laflamme and colleagues show that the transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) partially remuscularizes the scar of infarcted and appropriately immunosuppressed pigs. hESC-CM recipients exhibited frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. These graft-related tachyarrhythmias were found to be due to focal mechanisms rather than macro-reentry. Keywords: human embryonic stem cell-derived cardiomyocytes, pluripotent stem cells, myocardial infarction, ventricular tachyarrhythmias, electroanatomical mapping, MR