Electrical signals affect the cardiomyocyte transcriptome independently of contraction.

Cardiomyocytes in vivo are continuously subjected to electrical signals that evoke contractions and instigate drastic changes in the cells' morphology and function. Studies on how electrical stimulation affects the cardiac transcriptome have remained limited to a small number of heart-specific genes. Furthermore, these studies have ignored the interplay between the electrical excitation and the subsequent contractions. We carried out a genomewide assessment of the effects of electrical signaling on gene expression, while distinguishing between the effects deriving from the electrical pulses themselves and the effects instigated by the evoked contractions. Changes in gene expression in primary cultures of neonatal ventricular cardiomyocytes from Lewis Rattus norvegicus were investigated with microarrays and RT-quantitative PCR (QPCR). A series of experiments was included in which the culture medium was supplemented with the contraction inhibitor blebbistatin to allow for electrical stimulation in the absence of contraction. Electrical stimulation was shown to directly enhance calcium handling and induce cardiomyocyte differentiation by arresting cell division and activating key cardiac transcription factors as well as additional differentiation mechanisms such as wnt signaling. Several genes involved in metabolism were also directly activated by electrical stimulation. Furthermore, our data suggest that contraction exerts negative feedback on the transcription of various genes. Together, these observations indicate that intercellular electric currents between adjacent cardiomyocytes have an important role in cardiomyocyte development. They act at least partially through a pulse-specific gene expression program that is activated independently from the evoked contractions.

Making post-mortem implantable cardioverter defibrillator explantation safe.

AIMS: The aim of this study is to investigate whether protection with rubber or plastic gloves during post-mortem explantation of an implantable cardioverter defibrillator (ICD) offers enough protection for the explanting operator during a worst-case scenario (i.e. ICD shock). METHODS AND RESULTS: We investigated the insulating properties of rubber and plastic gloves (double layer) within the first 60 min exposure (mimicking the maximum time of an explantation procedure) to saline (simulating the effects of body fluids on the gloves). For latex gloves, we measured an increase in voltage up to 68.1 V (P < 0.0001), for neoprene a maximum voltage of 5.3 V (P = 0.245), and for plastic a voltage of 2.3 V within the first hour. If the exposure time to fluid did not exceed 50 min, a double pair of intact gloves made of latex, neoprene, or plastic constituted such a large resistance that the resting voltage over the operating person would not exceed 50 V. CONCLUSION: The use of intact medical gloves made of latex, neoprene, or plastic eliminates the potential electrical risk during explantation of an ICD. Two gloves on each hand offer sufficient protection. We will recommend the use of neoprene gloves.

Evaluation of cumulative effects of MR imaging on pacemaker systems at 1.5 Tesla.

BACKGROUND: The purpose of this study was to evaluate possible cumulative effects of repeated magnetic resonance imaging (MRI) examinations on pacemaker systems in patients with cardiac pacemakers. METHODS AND RESULTS: The records of pacemaker patients who underwent repetitive MRI examinations in our institution were reviewed to identify patients who underwent two or more MRI examinations at 1.5T of any anatomical region. Using these criteria, a total of 47 patients who underwent a total 171 MRI examinations were identified and included in this study. Institutional Review Board approval for all pacemaker investigations was obtained. Written informed consent was obtained from all patients. Pacemakers were interrogated immediately before and after MR imaging, and after 3 months, including measurement of pacing capture threshold (PCT), lead impedance (LI), and battery voltage (BV). PCT, LI, and BV were analyzed for changes dependant on the number of MRI exams performed. Mean changes over time and changes between first and last pacemaker interrogation of PCT, LI, and BV were calculated. A statistically significant (P < 0.05), but clinically irrelevant trend for decrease in PCT and BV was found. No significant or clinically relevant changes in LI were observed. CONCLUSION: In this first study, no clinically relevant, cumulative changes in PCT, LI, or BV could be detected in PM patients who underwent two or more MRI examinations. However, a careful benefit/risk evaluation, among other MRI- and pacemaker-related safety precautions, remains mandatory, as clinically relevant alterations to the PM system cannot be excluded by all means.

Strategy for safe performance of extrathoracic magnetic resonance imaging at 1.5 tesla in the presence of cardiac pacemakers in non-pacemaker-dependent patients: a prospective study with 115 examinations.

BACKGROUND: The purpose of the present study was to evaluate a strategy for safe performance of extrathoracic magnetic resonance imaging (MRI) in non-pacemaker-dependent patients with cardiac pacemakers. METHODS AND RESULTS: Inclusion criteria were presence of a cardiac pacemaker and urgent clinical need for an MRI examination. Pacemaker-dependent patients and those requiring examinations of the thoracic region were excluded. The study group consisted of 82 pacemaker patients who underwent a total of 115 MRI examinations at 1.5T. To minimize radiofrequency-related lead heating, the specific absorption rate was limited to 1.5 W/kg. All pacemakers were reprogrammed before MRI: If heart rate was <60 bpm, the asynchronous mode was programmed to avoid magnetic resonance (MR)-induced inhibition; if heart rate was >60 bpm, sense-only mode was used to avoid MR-induced competitive pacing and potential proarrhythmia. Patients were monitored with ECG and pulse oximetry. All pacemakers were interrogated immediately before and after the MRI examination and after 3 months, including measurement of pacing capture threshold (PCT) and serum troponin I levels. All MR examinations were completed safely. Inhibition of pacemaker output or induction of arrhythmias was not observed. PCT increased significantly from pre- to post-MRI (P=0.017). In 2 of 195 leads, an increase in PCT was only detected at follow-up. In 4 of 114 examinations, troponin increased from a normal baseline value to above normal after MRI, and in 1 case (troponin pre-MRI 0.02 ng/mL, post-MRI 0.16 ng/mL), this increase was associated with a significant increase in PCT. CONCLUSIONS: Extrathoracic MRI of non-pacemaker-dependent patients can be performed with an acceptable risk-benefit ratio under controlled conditions and by taking both MR- and pacemaker-related precautions.

Electrical stimulation of primary neonatal rat ventricular cardiomyocytes using pacemakers.

The study of gene regulation in cardiac myocytes requires a reliable in vitro model. However, monolayer cultures used for this purpose are typically not exposed to electrical stimulation, though this has been shown to strongly affect cardiomyocyte gene expression. Based on pacemakers for clinical use, we developed an easy-to-use portable system that allows the user to perform electro-stimulation of cardiomyocyte cultures in standard tissue incubators without the need for bulky equipment. In addition, we present a refined protocol for culturing high-purity cardiomyocyte cultures with excellent contractile properties for a wide variety of applications.

In vivo heating of pacemaker leads during magnetic resonance imaging.

AIMS: Magnetic resonance imaging (MRI) is well established as an important diagnostic tool in medicine. However, the presence of a cardiac pacemaker is usually regarded as a contraindication for MRI due to safety reasons. In this study, heating effects at the myocardium-pacemaker lead tip interface have been investigated in a chronic animal model during MRI at 1.5 Tesla. METHODS AND RESULTS: Pacemaker leads with additional thermocouple wires as temperature sensors were implanted in nine animals. Temperature increases of up to 20 degrees C were measured during MRI of the heart. Significant impedance and minor stimulation threshold changes could be seen. However, pathology and histology could not clearly demonstrate heat-induced damage. CONCLUSIONS: MRI may produce considerable heating at the lead tip. Changes of pacing parameters due to MRI could be seen in chronic experiments. Potential risk of tissue damage cannot be excluded even though no reproducible alterations at the histological level could be found.

Pacemaker reed switch behavior in 0.5, 1.5, and 3.0 Tesla magnetic resonance imaging units: are reed switches always closed in strong magnetic fields?

MRI is established as an important diagnostic tool in medicine. However, the presence of a cardiac pacemaker is usually regarded as a contraindication for MRI due to safety reasons. The aim of this study was to investigate the state of a pacemaker reed switch in different orientations and positions in the main magnetic field of 0.5-, 1.5-, and 3.0-T MRI scanners. Reed switches used in current pacemakers and ICDs were tested in 0.5-, 1.5-, and 3.0-T MRI scanners. The closure of isolated reed switches was evaluated for different orientations and positions relative to the main magnetic field. The field strengths to close and open the reed switch and the orientation dependency of the closed state inside the main magnetic field were investigated. The measurements were repeated using two intact pacemakers to evaluate the potential influence of the other magnetic components, like the battery. If the reed switches were oriented parallel to the magnetic fields, they closed at 1.0 +/- 0.2 mT and opened at 0.7 +/- 0.2 mT. Two different reed switch behaviors were observed at different magnetic field strengths. In low magnetic fields (< 50 mT), the reed switches were closed. However, in high magnetic fields (> 200 mT), the reed switches opened in 50% of all tested orientations. No difference between the three scanners could be demonstrated. The reed switches showed the same behavior whether they were isolated or an integral part of the pacemakers. The reed switch in a pacemaker or an ICD does not necessarily remain closed in strong magnetic fields at 0.5, 1.5, or 3.0 T and the state of the reed switch may not be predictable with certainty in clinical situations.

Pacing in high field cardiac magnetic resonance imaging:.

Currently, cardiac MRI is contraindicated in patients with an implanted pacemaker or ICD due to safety hazards. However, MRI is promising to play a key role in cardiac diagnostics in near future. This study examined a rat with an implanted pacemaker pacing at a rate of 460/min with high field cardiac MRI. This study showed that pacing during cardiac imaging at 7 Tesla was possible. The pacemaker program was not disturbed by the high field or the strong gradients (maximum dB/dt 400 mT/s). The only noticeable effect on the MRI signal was a signal void of 2 cm around the device.