Photobiomodulation for Blood Pressure and Heart Rate Reduction in Mastectomized Women on Hormone Blockers: A Randomized Controlled Trial.

Objective: To assess the impact of intravascular laser irradiation of blood (ILIB) on the primitive carotid artery (PCA) hemodynamic variables, specifically blood pressure (BP) and heart rate (HR), in mastectomized patients undergoing hormone blocker treatments. Materials and methods: This study is a controlled, experimental, and randomized clinical trial. Patients were allocated into two groups: the experimental group (G1)-patients who received ILIB therapy using a 660 nm laser targeted at the PCA, and the control group (G2)-patients who did not receive ILIB therapy. Clinical research was conducted weekly, with measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR. The Mann-Whitney U test for independent samples was used, with a significance level of α = 0.05. Results: Systemic photobiomodulation on the PCA did not demonstrate a statistically significant difference in relation to SBP and DBP. However, for HR, the p-value was <0.05, indicating a significant difference between G1 and G2. The initial mean p > decreased from 142.3 to 116.4 mmHg in G1, and from 130.4 to 119.8 mmHg in G2. The DBP varied from 78.8 to 72.8 mmHg in G1, and from 79.1 to 74.2 mmHg in G2. A statistically significant difference was observed in HR, decreasing from 81.3 to 62.06 bpm in G1, and changing minimally from 74.1 to 75.1 bpm in G2. A considerable reduction was present in the timing of application. Conclusions: ILIB therapy applied to the PCA induces a reduction in BP and, more notably, HR in mastectomized women using the tamoxifen or aromatase inhibitors.

Arousal-based pupil modulation is dictated by luminance.

Pupillometry has become a standard measure for assessing arousal state. However, environmental factors such as luminance, a primary dictator of pupillary responses, often vary across studies. To what degree does luminance interact with arousal-driven pupillary changes? Here, we parametrically assessed luminance-driven pupillary responses across a wide-range of luminances, while concurrently manipulating cognitive arousal using auditory math problems of varying difficulty. At the group-level, our results revealed that the modulatory effect of cognitive arousal on pupil size interacts multiplicatively with luminance, with the largest effects occurring at low and mid-luminances. However, at the level of individuals, there were qualitatively distinct individual differences in the modulatory effect of cognitive arousal on luminance-driven pupillary responses. Our findings suggest that pupillometry as a measure for assessing arousal requires more careful consideration: there are ranges of luminance levels that are more ideal in observing pupillary differences between arousal conditions than others.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0-10) was 7 (interquartile range, 6-7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722-1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Cardiac radiotherapy induces electrical conduction reprogramming in the absence of transmural fibrosis.

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.

Ambient-task combined lighting to regulate autonomic and psychomotor arousal levels without compromising subjective comfort to lighting.

BACKGROUND: Although evidence of both beneficial and adverse biological effects of lighting has accumulated, biologically favorable lighting often does not match subjectively comfortable lighting. By controlling the correlated color temperature (CCT) of ambient lights, we investigated the feasibility of combined lighting that meets both biological requirements and subjective comfort. METHODS: Two types of combined lightings were compared; one consisted of a high-CCT (12000 K) light-emitting diode (LED) panel as the ambient light and a low-CCT (5000 K) LED stand light as the task light (high-low combined lighting), and the other consisted of a low-CCT (4500 K) LED panel as the ambient light and the same low-CCT (5000 K) stand light as the task light (low-low combined lighting) as control. Ten healthy subjects (5 young and 5 elderly) were exposed to the two types of lighting on separate days. Autonomic function by heart rate variability, psychomotor performances, and subjective comfort were compared. RESULTS: Both at sitting rest and during psychomotor workload, heart rate was higher and the parasympathetic index of heart rate variability was lower under the high-low combined lighting than the low-low combined lighting in both young and elderly subject groups. Increased psychomotor alertness in the elderly and improved sustainability of concentration work performance in both age groups were also observed under the high-low combined lighting. However, no significant difference was observed in the visual-analog-scale assessment of subjective comfort between the two types of lightings. CONCLUSIONS: High-CCT ambient lighting, even when used in combination with low-CCT task lighting, could increase autonomic and psychomotor arousal levels without compromising subjective comfort. This finding suggests the feasibility of independent control of ambient and task lighting as a way to achieve both biological function regulation and subjective comfort.

Sex-dependent effects of genetic upregulation of activated protein C on delayed effects of acute radiation exposure in the mouse heart, small intestine, and skin.

Accidental exposure to ionizing radiation may lead to delayed effects of acute radiation exposure (DEARE) in many organ systems. Activated protein C (APC) is a known mitigator of the acute radiation syndrome. To examine the role of APC in DEARE, we used a transgenic mouse model with 2- to 3-fold increased plasma levels of APC (high in APC, APCHi). Male and female APCHi mice and wild-type littermates were exposed to 9.5 Gy γ-rays with their hind-legs (bone marrow) shielded from radiation to allow long-term survival. At 3 and 6 months after irradiation, cardiac function was measured with ultrasonography. At 3 months, radiation increased cardiac dimensions in APCHi males, while decreases were seen in wild-type females. At this early time point, APCHi mice of both sexes were more susceptible to radiation-induced changes in systolic function compared to wild-types. At 6 months, a decrease in systolic function was mainly seen in male mice of both genotypes. At 6 months, specimens of heart, small intestine and dorsal skin were collected for tissue analysis. Female APCHi mice showed the most severe radiation-induced deposition of cardiac collagens but were protected against a radiation-induced loss of microvascular density. Both male and female APCHi mice were protected against a radiation induced upregulation of toll-like receptor 4 in the heart, but this did not translate into a clear protection against immune cell infiltration. In the small intestine, the APCHi genotype had no effect on an increase in the number of myeloperoxidase positive cells (seen mostly in females) or an increase in the expression of T-cell marker CD2 (males). Lastly, both male and female APCHi mice were protected against radiation-induced epidermal thickening and increase in 3-nitrotyrosine positive keratinocytes. In conclusion, prolonged high levels of APC in a transgenic mouse model had little effects on indicators of DEARE in the heart, small intestine and skin, with some differential effects in male compared to female mice.

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling.

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9-2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.

The effectiveness of far-infrared irradiation on foot skin surface temperature and heart rate variability in healthy adults over 50 years of age: A randomized study.

BACKGROUND: Far-infrared irradiation (FIR) is used in the medical field to improve wound healing, hemodialysis with peripheral artery occlusive disease, and osteoarthritis but seldom used in ameliorating poor lower extremity circulation. The purpose of this study was to evaluate the effect of FIR on changes in foot skin surface temperature (FSST) and autonomic nerve system (ANS) activity to evaluate its effectiveness in improving lower limb circulation. METHODS: A randomized controlled study was conducted. Subjects (n = 44), all over the age of 50 years and satisfying the inclusion criteria, were randomly allocated into 2 groups. The intervention group received FIR on a lower limb for 40 minutes and the control group received no intervention. Left big toe (LBT), right big toe (RBT), left foot dorsal (LFD), right foot dorsal (RFD) surface skin temperature, autonomic nervous activity, and blood pressure were assessed. RESULTS: The main results were skin surface temperature at the LBT increased from 30.8 ±â€Š0.4°C to 34.8 ±â€Š0.4°C, at RBT increased from 29.6 ±â€Š0.4°C to 35.3 ±â€Š0.4°C and LFD increased from 31.9 ±â€Š0.3°C to 36.4 ±â€Š0.4°C, RFD increased from 30.7 ±â€Š0.3°C to 37.7 ±â€Š0.2°C. FIR caused a significant increase of the FSST ranging in a 4°C to 7°C increase after 40 minutes irradiation (P < .001). The ANS low-frequency (LF) and high-frequency (HF) activity showed a statistically significant increase in the FIR group (P < .05) but not the LF/HF ratio. CONCLUSION: FIR significantly increased the FSST from between 4°C and 7°C after 40 minutes irradiation, which might improve lower extremity circulation and regulation of ANS activity.

Radiofrequency electromagnetic field affects heart rate variability in rabbits.

The aim of this study was to assess the effects of radiofrequency electromagnetic field (RF EMF) on heart rate variability (HRV) in rabbits with intensity slightly exceeding the limits for occupations. Totally 21 New Zealand white rabbits divided into two groups were used in this double-blind study. The first group of animals without general anesthesia was subjected to HRV examination under exposure to a device generated RF EMF source (frequency 1788 MHz, intensity 160 V/m, lasting 150 min.). The second group (premedications + alpha chloralose mg/kg) underwent the same protocol under the exposure to the real RF EMF signal from the base stations of mobile providers (frequency range 1805 - 1870 MHz - corresponding to the downlink signal of Slovak mobile providers, 160 V/m, 150 min., respectively). Individual 5 min records were used to analyze the HRV parameters: heart rate and root Mean Square of the Successive Differences (rMSSD) for time domain analysis and spectral powers in the low (LF-VFS) and high frequency (HF-VFS) bands for frequency domain analysis. Our study revealed the increased in HRV parameters (HF-HRV, rMSSD) associated with lower heart rate indicating increased cardiac vagal control under the exposure to RF EMF in experimental methods.

The effect of HF-rTMS over the left DLPFC on stress regulation as measured by cortisol and heart rate variability.

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.

Exposure to cell phones reduces heart rate variability in both normal-weight and obese normotensive medical students.

BACKGROUND: We investigated and compared the effect of the radiofrequency electromagnetic field (RF-EM) emitted by a cell phone on the electrocardiogram and heart rate variability (HRV) of normotensive normal-weight and obese medical students. METHOD: Twenty medical student volunteers, normal weight (age = 23 ± 2, BMI = 23.05 ± 1.72) or obese (age = 24 ± 2, BMI = 32.39 ± 4.78), were exposed to a cell phone (1) close to the heart in silent mode, no ringing or vibrating; (2) close to the heart in ring and vibration mode; (3) next to the ear (brain) while listening; and (4) next to the ear while listening and speaking. RESULTS: The average basal HR of obese students significantly increased, while the PR interval; time domains, including standard deviation (SD) of all normal R-R intervals (SDNN), mean of the SD of all normal R-R intervals (SDNNi), SD of the average of normal R-R intervals (SDANN), and percentage of R-R intervals at least 50 ms different from the previous interval (pNN50); and high-power frequency (HF) decreased. The LF/HF ratio also significantly increased. The SDNN, SDNNi, SDANN, pNN50, and HF levels significantly decreased and the LF/HF significantly increased in normal-weight and obese individuals only when the phone was near the apex of the heart in ring and vibration mode. All changes were more profound in obese students. CONCLUSION: Keeping the phone in a chest pocket reduced the HRV of normal-weight and obese medical students and exaggerated the effect of obesity on sympathetic activation.

Difference in autonomic nervous effect of blue light depending on the angle of incidence on the eye.

OBJECTIVE: Blue light has been attributed to the adverse biological effects caused by the use of smartphones and tablet devices at night. However, it is not realistic to immediately avoid nighttime exposure to blue light in the lifestyle of modern society, so other effective methods should be investigated. Earlier studies reported that inferior retinal light exposure causes greater melatonin suppression than superior retinal exposure. We examined whether the autonomic responses to blue light depends on the angle of incidence to the eye. RESULTS: In eight healthy subjects, blue light from organic electroluminescent lighting device (15.4 lx at subjects' eye) was exposed from 6 angles (0º, 30º, 45º, 135º, 150º, and 180º) for 5 min each with a 10-min interval of darkness. After adjusting the order effect of angles, however, no significant difference in heart rate or autonomic indices of heart rate variability with the angle of incidence was detected in this study.

Photobiomodulation induces hypotensive effect in spontaneously hypertensive rats.

To evaluate whether acute photobiomodulation can elicit a hypotensive effect in spontaneously hypertensive rats (SHR). Male SHR were submitted to the implantation of a polyethylene cannula into the femoral artery. After 24 h, baseline measurements of the hemodynamic parameters: systolic, diastolic, and mean arterial pressure, and heart rate were accomplished for 1 h. Afterwards, laser application was simulated, and the hemodynamic parameters were recorded for 1 h. In the same animal, the laser was applied at six different positions of the rat's abdomen, and the hemodynamic parameters were also recorded until the end of the hypotensive effect. The irradiation parameters were red wavelength (660 nm); average optical power of 100 mW; 56 s per point (six points); spot area of 0.0586 cm2; and irradiance of 1.71 W/cm2 yielding to a fluency of 96 J/cm2 per point. For measuring plasma NO levels, blood was collected before the recording, as well as immediately after the end of the mediated hypotensive effect. Photobiomodulation therapy was able to reduce the systolic arterial pressure in 69% of the SHR submitted to the application, displaying a decrease in systolic, diastolic, and mean arterial pressure. No change in heart rate was observed. Nevertheless, there was an increase in serum nitric oxide levels in the SHR responsive to photobiomodulation. Our results suggest that acute irradiation with a red laser at 660 nm can elicit a hypotensive effect in SHR, probably by a mechanism involving the release of NO, without changing the heart rate.

Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation.

Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 µM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and γ-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.

Emergence of consistent intra-individual locomotor patterns during zebrafish development.

The analysis of larval zebrafish locomotor behavior has emerged as a powerful indicator of perturbations in the nervous system and is used in many fields of research, including neuroscience, toxicology and drug discovery. The behavior of larval zebrafish however, is highly variable, resulting in the use of large numbers of animals and the inability to detect small effects. In this study, we analyzed whether individual locomotor behavior is stable over development and whether behavioral parameters correlate with physiological and morphological features, with the aim of better understanding the variability and predictability of larval locomotor behavior. Our results reveal that locomotor activity of an individual larva remains consistent throughout a given day and is predictable throughout larval development, especially during dark phases, under which larvae demonstrate light-searching behaviors and increased activity. The larvae's response to startle-stimuli was found to be unpredictable, with no correlation found between response strength and locomotor activity. Furthermore, locomotor activity was not associated with physiological or morphological features of a larva (resting heart rate, body length, size of the swim bladder). Overall, our findings highlight the areas of intra-individual consistency, which could be used to improve the sensitivity of assays using zebrafish locomotor activity as an endpoint.

Non-visual effects of diurnal exposure to an artificial skylight, including nocturnal melatonin suppression.

BACKGROUND: Recently, more consideration is being given to the beneficial effects of lighting on the maintenance and promotion of the health and well-being of office occupants in built environments. A new lighting technology using Rayleigh scattering has made it possible to simulate a blue sky. However, to date, no studies have examined the possible beneficial effects of such artificial skylights. The aims of this study were to examine the non-visual effects of artificial skylights and conventional fluorescent lights in a simulated office environment and to clarify the feature effects of the artificial skylights. METHODS: Participants were 10 healthy male adults. Non-visual effects were evaluated based on brain arousal levels (α-wave ratio and contingent negative variation [CNV]), autonomic nervous activity (heart rate variability [HRV]), work performance, and subjective responses during daytime exposure to either an artificial skylight or fluorescent lights, as well as nocturnal melatonin secretion. RESULTS: Subjective evaluations of both room lighting-related "natural" and "attractive" items and the "connected to nature" item were significantly higher with the skylight than with the fluorescent lights. Cortical arousal levels obtained from the early component of the CNV amplitude were significantly lower with the skylight than with the fluorescent lights, whereas α-wave ratio and work performance were similar between the two light sources. The HRV evaluation showed that sympathetic nerve tone was lower and parasympathetic nerve tone was higher, both significantly, for the skylight than for the fluorescent lights during daytime. Nocturnal melatonin secretion was significantly greater before and during light exposure at night under the daytime skylight than under the fluorescent lights. CONCLUSIONS: Our results suggest that artificial skylights have some advantages over conventional fluorescent lights in maintaining ordinary work performance during daytime with less psychological and physiological stress. The findings also suggest that the artificial skylights would enable built environments to maintain long-term comfort and productivity.

Consequences of low-intensity light at night on cardiovascular and metabolic parameters in spontaneously hypertensive rats 1.

Circadian rhythms are an inherent property of physiological processes and can be disturbed by irregular environmental cycles, including artificial light at night (ALAN). Circadian disruption may contribute to many pathologies, such as hypertension, obesity, and type 2 diabetes, but the underlying mechanisms are not understood. Our study investigated the consequences of ALAN on cardiovascular and metabolic parameters in spontaneously hypertensive rats, which represent an animal model of essential hypertension and insulin resistance. Adult males were exposed to a 12 h light - 12 h dark cycle and the ALAN group experienced dim light at night (1-2 lx), either for 2 or 5 weeks. Rats on ALAN showed a loss of light-dark variability for systolic blood pressure, but not for heart rate. Moreover, a gradual increase of systolic blood pressure was recorded over 5 weeks of ALAN. Exposure to ALAN increased plasma insulin and hepatic triglyceride levels. An increased expression of metabolic transcription factors, Pparα and Pparγ, in the epididymal fat and a decreased expression of Glut4 in the heart was found in the ALAN group. Our results demonstrate that low-intensity ALAN can disturb blood pressure control and augment insulin resistance in spontaneously hypertensive rats, and may represent a serious risk factor for cardiometabolic diseases.

Flexible and precise control of cardiac rhythm with blue light.

Optogenetics is an innovative method for precise control of biological function, which makes light manipulation displays more advantages than electric energy because of contactless spatial flexibility and cell-to-cell synchronous communication. The aim of this study was to perform different illumination modes with blue laser to investigate optical control of the mice hearts. In this study, we transfected the light sensitive protein ChR2(H134R) into mouse hearts, which were illuminated with a 473 nm laser on the Langendorff apparatus. We recorded all the signals of electrograms (EGs), epicardium monophasic action potential (MAPs) and light output signals to analyze myocardial electrical activity. EGs and MAP showed that ChR2 expression in the heart can be flexibly controlled by blue light across different illumination sites with corresponding triggered ectopic rhythm. Illumination intensity, pulse duration, and impulse frequency were associated with the light capture rate. Continuous illumination with the threshold intensity on the left ventricle had little influence on sinus rhythm and ventricular electrophysiology. Our results support that flexible control of the cardiac rhythm with optogenetics provides an innovative approach to cardiac research and therapy.

Biological Cardiac Tissue Effects of High-Energy Heavy Ions - Investigation for Myocardial Ablation.

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.