ß-Adrenergic response is counteracted by extremely-low-frequency pulsed electromagnetic fields in beating cardiomyocytes.

Proper ß-adrenergic signaling is indispensable for modulating heart frequency. Studies on extremely-low-frequency pulsed electromagnetic field (ELF-PEMF) effects in the heart beat function are contradictory and no definitive conclusions were obtained so far. To investigate the interplay between ELF-PEMF exposure and ß-adrenergic signaling, cultures of primary murine neonatal cardiomyocytes and of sinoatrial node were exposed to ELF-PEMF and short and long-term effects were evaluated. The ELF-PEMF generated a variable magnetic induction field of 0-6mT at a frequency of 75Hz. Exposure to 3mT ELF-PEMF induced a decrease of contraction rate, Ca(2+) transients, contraction force, and energy consumption both under basal conditions and after ß-adrenergic stimulation in neonatal cardiomyocytes. ELF-PEMF exposure inhibited ß-adrenergic response in sinoatrial node (SAN) region. ELF-PEMF specifically modulated ß2 adrenergic receptor response and the exposure did not modify the increase of contraction rate after adenylate cyclase stimulation by forskolin. In HEK293T cells transfected with ß1 or ß2 adrenergic receptors, ELF-PEMF exposure induced a rapid and selective internalization of ß2 adrenergic receptor. The ß-adrenergic signaling, was reduced trough Gi protein by ELF-PEMF exposure since the phosphorylation level of phospholamban and the PI3K pathway were impaired after isoproterenol stimulation in neonatal cardiomyocytes. Long term effects of ELF-PEMF exposure were assessed in cultures of isolated cardiomyocytes. ELF-PEMF counteracts cell size increase, the generation of binucleated of cardiomyocytes and prevents the up-regulation of hypertrophic markers after ß-adrenergic stimulation, indicating an inhibition of cell growth and maturation. These data show that short and long term exposure to ELF-PEMF induces a reduction of cardiac ß-adrenergic response at molecular, functional and adaptative levels.

Pathological changes in the sinoatrial node tissues of rats caused by pulsed microwave exposure.

To observe microwave induced dynamic pathological changes in the sinus nodes, wistar rats were exposed to 0, 5, 10, 50 mW/cm2 microwave. In 10 and 50 mW/cm2 groups, disorganized sinoatrial node cells, cell swelling, cytoplasmic condensation, nuclear pyknosis, and anachromasis, swollen, and empty mitochondria, and blurred and focally dissolved myofibrils could be detected from 1 to 28 d, while reduced parenchymal cells, increased collagen fibers, and extracellular matrix remodeling of interstitial cells were observed from 6 to 12 months. In conclusion, 10 and 50 mW/cm2 microwave could cause structural damages in the sinoatrial node and extracellular matrix remodeling in rats.

DETERMINATION OF NATIONAL DIAGNOSTIC REFERENCE LEVELS IN COMPUTED TOMOGRAPHY EXAMINATIONS OF IRAN BY A NEW QUALITY CONTROL-BASED DOSE SURVEY METHOD.

National diagnostic reference levels (NDRLs) of Iran were determined for the four most common CT examinations including head, sinus, chest and abdomen/pelvis. A new 'quality control (QC)-based dose survey method', as developed by us, was applied to 157 CT scanners in Iran (2014-15) with different slice classes, models and geographic spread across the country. The NDRLs for head, sinus, chest and abdomen/pelvis examinations are 58, 29, 12 and 14 mGy for CTDIVol and 750, 300, 300 and 650 mGy.cm for DLP, respectively. The 'QC-based dose survey method' was further proven that it is a simple, accurate and practical method for a time and cost-effective NDRLs determination. One effective approach for optimization of the CT examination protocols at the national level is the provision of an adequate standardized training of the radiologists, technicians and medical physicists on the patient radiation protection principles and implementation of the DRL concept in clinical practices.

Sinoatrial node toxicity after stereotactic ablative radiation therapy to lung tumors.

PURPOSE: Stereotactic ablative radiation therapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR. METHODS AND MATERIALS: We conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2 cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28 months. Time to toxicity was defined from start of SABR. RESULTS: Of 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6 months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation-induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24 months' follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity. CONCLUSION: While uncommon, SAN toxicity from SABR to right-sided central thoracic tumors should be recognized and followed in future studies.

Positive chronotropic responses of rabbit sino-atrial node cells to flash photolysis of caged isoproterenol and cyclic AMP.

The kinetics of onset and the intracellular biochemical signalling mechanisms which are responsible for the positive chronotropic effect of sympathetic stimulation in rabbit cardiac pacemaker cells were examined by using flash photolysis of caged isoproterenol (ISO) and cyclic AMP (cAMP). When caged ISO (10 microM) was present in the superfusate, a single ultraviolet flash caused gradual increases in the spontaneous beating frequency and action potential height of S-A node cells. Both these effects developed after an initial latency of approximately 5 s. Photorelease of ISO also increased the L-type Ca2+ current (ICa-L) with a time-course similar to that of the changes in action potential waveform and heart rate. All of these ISO-induced effects were blocked completely by 1 microM propranolol, demonstrating that they were beta-adrenergic responses. Flash photolysis of caged cAMP (50 microM) also resulted in increased firing frequency and ICa-L. However, these responses to cAMP developed with little or no latency. Intracellular dialysis with a selective inhibitor of the cAMP-dependent protein kinase, Rp-cAMPS, completely abolished the increase in ICa-L demonstrating that it is mediated exclusively via cAMP-dependent activation of protein kinase A, as opposed to a direct G-protein mediated mechanism.

Cardiac electrophysiology: theoretical considerations of a potential target for weak electromagnetic field effects.

With the widespread introduction of extra high voltage power transmission lines in the 1960s, and subsequent to early reports from Soviet Union scientists about health risks for transformer station personnel, public concern regarding the effects of electromagnetic fields (EMFs) on biological function has given rise to a large number of investigations and legislation to limit domestic and occupational exposure to EMFs. The underlying rationale for concern is related to the fact that living cells are electrically active, which makes them potentially vulnerable to electromagnetic interference. In the heart, electrical activity is crucial in coordinating the contraction of millions of cardiac cells, and disturbances in cardiac electrical activity, also known as arrhythmias, are often life threatening. Electrical fields induced in the heart by weak external EMFs (such as those encountered in a domestic setting) are understood to be at least 2 orders of magnitude smaller (< 1%) than those that occur naturally as an intrinsic consequence of cardiac activity. Using quantitative models of cardiac cellular electrophysiology, the effect of weak (1%) manipulation of key current mechanisms that give rise to the electrical activity of the heart is therefore assessed.

Rapporteur report: other tissues.

This report covers the session devoted to 'other tissues'. It considers the effects of internal electric fields such as those induced by exposure to weak, extremely low frequency (ELF) electromagnetic fields, on cardiac physiology, neuroendocrine (pineal) function and on the processes of tissue repair and embryonic development. Summaries are provided for each of the papers presented, and the major aspects of the plenary session are discussed. Overall, these tissues and processes were not considered to be sensitive to the direct effects of weak ELF fields, although indirect effects may occur via field induced changes to the central nervous system.

Brady-tachycardia syndrome after radiotherapy for lung cancer. Assessment by computed tomography and carbon-11 methionine positron emission tomography.

A 74-year-old male who had received radiotherapy (total 54 Gy) for right lung cancer 7 months earlier developed a symptomatic brady-tachycardia syndrome requiring the implantation of a permanent pacemaker. Chest CT showed a pulmonary tumor of 2-cm diameter in the right lower lobe with direct extension into the surrounding tissue, suggesting the possibility of cardiac invasion. Carbon-11 methionine positron emission tomography (PET) indicated the absence of visible invasion of the heart with lung cancer. The bradytachycardia syndrome, therefore, was considered to be associated with sinus node injury due to radiation. Carbon-11 methionine PET metabolic imaging might play an important role in evaluating noninvasively the cause of the arrhythmia in this patient.

Comparative effects of extremely high power microwave pulses and a brief CW irradiation on pacemaker function in isolated frog heart slices.

The existence of specific bioeffects due to high peak power microwaves and their potential health hazards are among the most debated but least explored problems in microwave biology. The present study attempted to reveal such effects by comparing the bioeffects of short trains of extremely high power microwave pulses (EHPP, 1 micros width, 250-350 kW/g, 9.2 GHz) with those of relatively low power pulses (LPP, 0.5-10 s width, 3-30 W/g, 9.2 GHz). EHPP train duration and average power were made equal to those of an LPP; therefore both exposure modalities produced the same temperature rise. Bioeffects were studied in isolated, spontaneously beating slices of the frog heart. In most cases, a single EHPP train or LPP immediately decreased the inter-beat interval (IBI). The effect was proportional to microwave heating, fully reversible, and easily reproducible. The magnitude and time course of EHPP- and LPP-induced changes always were the same. No delayed or irreversible effects of irradiation were observed. The same effect could be repeated in a single preparation numerous times with no signs of adaptation, sensitization, lasting functional alteration, or damage. A qualitatively different effect, namely, a temporary arrest of preparation beats, could be observed when microwave heating exceeded physiologically tolerable limits. This effect also did not depend on whether the critical temperature rise was produced by LPP or EHPP exposure. Within the studied limits, we found no indications of EHPP-specific bioeffects. EHPP- and LPP-induced changes in the pacemaker rhythm of isolated frog heart preparation were identical and could be entirely attributed to microwave heating.