ARRHYTHMOGENESIS AND CONDUCTION PROPERTIES OF CARDIOMYOCYTES IN RESPONSE TO DYSSYNCHRONOUS MECHANICAL AND ELECTRICAL STIMULATION

Many cardiac therapeutic modalities, including pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices, are used to treat abnormalities in cardiac function and conduction. Both electrical and mechanical dyssynchrony can have deleterious effects including reduced cardiac output and an increased susceptibility to cardiac arrhythmias. It is postulated that electro-mechanical dyssynchrony may contribute to the susceptibility of the heart to cardiac arrhythmias. In this study, a novel system was developed to study these effects by altering the electro-mechanical activation sequence in cultured neonatal rat cardiomyocyte monolayers by dyssynchronously stimulating the monolayers with applied electrical fields and pulsatile mechanical strain. Specifically, optical mapping was utilized to compare action potential duration and quantify arrhythmia susceptibility of cardiomyocytes subjected to pulsatile mechanical strain, electrical stimulation, and dyssynchronous electrical and mechanical stimulation. This system provides a method to evaluate changes in cardiomyocyte conduction properties due to altered electro-mechanical coupling and the subsequent impact on arrhythmogenesis

Electromagnetic interference of GSM mobile phones with the implantable deep brain stimulator, ITREL-III

BACKGROUND: The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz) and 10 different 1800 MHz GSM (Global System for Mobile Communications) mobile phones. METHODS: All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. RESULTS: Despite a maximum transmitted peak power of mobile phones of 1 Watt (W) at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. CONCLUSION: These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant

Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20 drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16 in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP, arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for the four remaining drugs could be due to differences in relative levels of expression of individual ion channels. iPSC-CMs responded consistently to human ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias) and calcium channel blocking drugs (APD shortening and prevention of arrhythmias), with a more variable response to late sodium current blocking drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia prediction under CiPA, where iPSC-CM results would serve as a check to ion channel and in silico modeling prediction of proarrhythmic risk. A multi-site validation study is warranted

Temperature measurement on neurological pulse generators during MR scans

According to manufacturers of both magnetic resonance imaging (MRI) machines, and implantable neurological pulse generators (IPGs), MRI is contraindicated for patients with IPGs. A major argument for this restriction is the risk to induce heat in the leads due to the electromagnetic field, which could be dangerous for the surrounding brain parenchyma. The temperature change on the surface of the case of an ITREL-III (Medtronic Inc., Minneapolis, MN) and the lead tip during MRI was determined. An anatomical realistic and a cubic phantom, filled with phantom material mimicking human tissue, and a typical lead configuration were used to imitate a patient who carries an IPG for deep brain stimulation. The measurements were performed in a 1.5 T and a 3.0 T MRI. 2.1°C temperature increases at the lead tip uncovered the lead tip as the most critical part concerning heating problems in IPGs. Temperature increases in other locations were low compared to the one at the lead tip. The measured temperature increase of 2.1°C can not be considered as harmful to the patient. Comparison with the results of other studies revealed the avoidance of loops as a practical method to reduce heating during MRI procedures