Regional ion channel gene expression heterogeneity and ventricular fibrillation dynamics in human hearts.

RATIONALE: Structural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role. OBJECTIVES: To define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics. METHODS AND RESULTS: High throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p<0.05) were identified in the expression of 23 genes in the myopathic LV and 32 genes in the myopathic RV. Within the myopathic hearts significant regional (LV vs septum vs RV) expression differences were observed for 13 subunits: Nav1.1, Cx43, Ca3.1, Cavalpha2delta2, Cavbeta2, HCN2, Na/K ATPase-1, CASQ1, CASQ2, RYR2, Kir2.3, Kir3.4, SUR2 (p<0.05). In a subset of genes we demonstrated differences in protein expression between control and myopathic hearts, which were concordant with the mRNA expression profiles for these genes. Variability in the expression of Cx43, hERG, Na(+)/K(+) ATPase ss1 and Kir2.1 correlated to variability in local VF dynamics (p<0.001). To better understand the contribution of multiple ion channel changes on VF frequency, simulations of a human myocyte model were conducted. These simulations demonstrated the complex nature by which VF dynamics are regulated when multi-channel changes are occurring simultaneously, compared to known linear relationships. CONCLUSIONS: Ion channel expression profile in myopathic human hearts is significantly altered compared to normal hearts. Multi-channel ion changes influence VF dynamic in a complex manner not predicted by known single channel linear relationships

Radiofrequency cardiac ablation with catheters placed on opposing sides of the ventricular wall: Computer modelling comparing bipolar and unipolar modes

Purpose: The aim of this study was to compare the efficacy of bipolar (BM) vs. unipolar (UM) mode of radiofrequency ablation (RFA) in terms of creating transmural lesions across the interventricular septum (IVS) and ventricular free wall (VFW). Materials and methods: We built computational models to study the temperature distributions and lesion dimensions created by BM and UM on IVS and VFW during RFA. Two different UM types were considered: sequential (SeUM) and simultaneous (SiUM). The effect of ventricular wall thickness, catheter misalignment, epicardial fat, and presence of air in the epicardial space were also studied. Results: Regarding IVS ablation, BM created transmural and symmetrical lesions for wall thicknesses up to 15 mm. SeUM and SiUM were not able to create transmural lesions with IVS thicknesses >= 12.5 and 15 mm, respectively. Lesions were asymmetrical only with SeUM. For VFW ablation, BM also created transmural lesions for wall thicknesses up to 15 mm. However, with SeUM and SiUM transmurality was obtained for VFW thicknesses <= 7.5 and 12.5 mm, respectively. With the three modes, VFW lesions were always asymmetrical. In the scenario with air or a fat tissue layer on the epicardial side, only SiUM was capable of creating transmural lesions. Overall, BM was superior to UM in IVS and VFW ablation when the catheters were not aligned. Conclusions: Our findings suggest that BM is more effective than UM in achieving transmurality across both ventricular sites, except in the situation of the epicardial catheter tip surrounded by air or placed over a fat tissue layer.This work received financial support from the Spanish 'Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion' (TEC2011-27133-C02-01), and from the Universitat Politecnica de Valencia (PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of a Grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Koruth, J.; D'avila, A.; Berjano, E. (2014). Radiofrequency cardiac ablation with catheters placed on opposing sides of the ventricular wall: Computer modelling comparing bipolar and unipolar modes. International Journal of Hyperthermia. 30(6):372-384. https://doi.org/10.3109/02656736.2014.949878S372384306SIVAGANGABALAN, G., BARRY, M. A., HUANG, K., LU, J., POULIOPOULOS, J., THOMAS, S. P., … KOVOOR, P. (2010). Bipolar Ablation of the Interventricular Septum is More Efficient at Creating a Transmural Line than Sequential Unipolar Ablation. Pacing and Clinical Electrophysiology, 33(1), 16-26. doi:10.1111/j.1540-8159.2009.02602.xNagashima, K., Watanabe, I., Okumura, Y., Ohkubo, K., Kofune, M., Ohya, T., … Hirayama, A. (2011). Lesion Formation by Ventricular Septal Ablation With Irrigated Electrodes. 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The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases

Axillary vein access using ultrasound guidance, Venography or Cephalic Cutdown - What is the optimal access technique for insertion of pacing leads?

We reviewed the different approaches used for central vein access during insertion of cardiac implantable electronic devices. The benefits and hazards of each approach (cephalic vein cutdown, axillary vein cannulation using venography and ultrasound) are discussed. Each approach has its advantages and hazards that need to be considered for the individual patient and balanced against the skills of the operator. The benefits of ultrasound guided venous access in reducing radiation exposure to the patient and implanter, avoiding the need for angiographic contrast and in minimizing the risk of pneumothorax and inadvertent arterial puncture are highlighted. Trainees should be taught each approach to deal with patient variability. Ultrasound guidance should be considered as a mainstream option for most patients