Long-term effects of photobiomodulation therapy on blood pressure in obese rats induced by a high-fat diet.

The main cardiovascular disease risk associated with obesity is hypertension. The therapeutic use of photobiomodulation therapy (PBM) is suggested for the treatment of wound healing, osteoarthritis, and arterial diseases. However, few studies have measured how red laser (at 660 nm) acts over hypertension, and any of those studies used experimental obesity model. The aim of the study was an attempt to evaluate the long-term effect of PBM on systolic blood pressure in an animal model of obesity, induced by a high-fat diet (HFD). Our results indicate that PBM carried out 3 days a week was able to prevent the increase in blood pressure (133.75 ± 4.82 mmHg, n = 8) induced by a high-fat diet (150.00 ± 4.57 mmHg, n = 8; p < 0.05), restore nitric oxide levels (control: 31.7 ± 5.5 µM, n = 8; HFD + PBM: 29.9 ± 3.7 µM, n = 8 > HFD: 22.2 ± 2.9 µM, n = 8, p < 0.05), decrease lipoperoxidation (control: 1.65 ± 0.25 nM, n = 8; HFD + PBM: 2.05 ± 0.55 nM, n = 8 < HFD: 3.20 ± 0.47 nM, n = 8; p < 0.05), and improve endothelial function (pD2 control: 7.39 ± 0.08, n = 8 > pD2 HFD + PBM: 7.15 ± 0.07, n = 8 > HFD: 6.94 ± 0.07, n = 8; p < 0.05). Our results indicate that PBM prevents the elevation of blood pressure in an obese animal model by a mechanism that involves improvement of endothelial function through an antioxidant effect.

[Clinical effect, changes in the lipid structure of the erythrocyte membrane and microcirculation in patients with arterial hypertension in combination with coronary heart disease under the influence of laser therapy]. / Klinicheskii effekt, izmenenie lipidnoi struktury eritrotsitarnoi membrany i mikrotsirkulyatsii u bol'nykh arterial'noi gipertoniei v sochetanii s ishemicheskoi bolezn'yu serdtsa pod vliyaniem lazeroterapii.

The high prevalence of the combination of arterial hypertension (AH) with coronary heart disease (CHD) suggests the improvement of their treatment methods. In this regard, it is of interest to assess the dynamics of the clinical picture of patients against the background of pathogenetically determined subcellular and systemic changes under the influence of laser therapy (LT). OBJECTIVE: To evaluate the clinical effect of LT in patients with hypertension in combination with coronary artery disease and trace its relationship with the dynamics of the structure of the lipid bilayer of the erythrocyte membrane and changes in the microvascular bed. MATERIAL AND METHODS: We examined 65 male patients (mean age 50.9±6.3 years) with II-III degree AH in combination with coronary artery disease with angina pectoris. Among them, 40 patients received a 10-day course of LT, and 25 patients underwent simulated laser irradiation. At the initial stage and after 1 month, all patients underwent a bicycle exercise test, a study of the lipid composition of the erythrocyte membrane, including the main fractions of phospholipids and free cholesterol, as well as the level of intracellular Ca2+ and lipid peroxidation products - malondialdehyde and diene conjugates. Microcirculation was assessed using the method of conjunctival biomicroscopy. RESULTS: One month after the course of LT, patients showed a significant increase in exercise tolerance by 37.8%, a decrease in systolic blood pressure with a standard load by 9.9%. The improvement of the clinical picture occurred against the background of a decrease in the activity of lipid peroxidation and structural changes in the cell membrane: an increase in polyunsaturated fractions of phospholipids and a decrease in the cholesterol content, as well as a decrease in the Ca2+ level in the cell from 0.23 [0.19; 0.32] to 0.20 [0.16; 0.26] mmol/l. The results of the analysis of conjunctival biomicroscopy demonstrated a statistically significant decrease in the ratio of arteriolovenular calibers, a limitation of the severity of sludge syndrome by 59%, and an almost twofold (from 3.9±0.52 to 7.2±1.23 cap/mm2) increase in capillary density. CONCLUSION: The data obtained showed that in patients with hypertension in combination with coronary artery disease, LT causes positive changes in the lipid structure of the cell membrane and microcirculation parameters, which is accompanied by a hypotensive effect and an improvement in the clinical and functional state of patients.

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.

Energy-dependent effect trial of photobiomodulation on blood pressure in hypertensive rats.

The main purpose of this work was to construct an energy-dependent response curve of photobiomodulation on arterial pressure in hypertension animal model. To reach this objective, we have used a two-kidney one clip (2K-1C) rat model. Animals received acute laser light irradiation (660 nm) on abdominal region using different energy (0.6, 1.8, 3.6, 7.2, 13.8, 28.2, 55.8, and 111.6 J), the direct arterial pressure was measured by femoral cannulation, and systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), and time of effect were obtained. Our results indicated that 660 nm laser light presents an energy-dependent hypotensive effect, and 28.2 J energy irradiation reached the maximum hypotensive effect, inducing a decreased SAP, DAP, and HR (decrease in SAP: - 19.23 ± 1.82 mmHg, n = 11; DAP: - 9.57 ± 2.23 mmHg, n = 11; HR: - 39.15 ± 5.10 bpm, n = 11; and time of hypotensive effect: 3068.00 ± 719.00 s, n = 11). The higher energy irradiation evaluated (111.6 J) did not induce a hypotensive effect and induced an increase in HR (21.69 ± 7.89 bpm, n = 7). Taken together, our results indicate that red laser energy irradiation from 7.2 to 55.8 J is the effective therapeutic window to reduce SAP, DAP, MAP, and HR and induce a long-lasting hypotensive effect in rats, with effect loss at higher energy irradiation (111.6 J).

Enlarged perivascular spaces and florbetapir uptake in patients with intracerebral hemorrhage.

PURPOSE: Enlarged perivascular spaces in the centrum semiovale (CSO-EPVS) have been linked to cerebral amyloid angiopathy (CAA). To get insight into the underlying mechanisms of this association, we investigated the relationship between amyloid-ß deposition assessed by 18F-florbetapir PET and CSO-EPVS in patients with acute intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled 18 patients with lobar ICH (suggesting CAA) and 20 with deep ICH (suggesting hypertensive angiopathy), who underwent brain MRI and 18F-florbetapir PET. EPVS were assessed on MRI using a validated 4-point visual rating scale in the centrum semiovale and the basal ganglia (BG-EPVS). PET images were visually assessed, blind to clinical and MRI data. We evaluated the association between florbetapir PET positivity and high degree (score> 2) of CSO-EPVS and BG-EPVS. RESULTS: High CSO-EPVS degree was more common in patients with lobar ICH than deep ICH (55.6% vs. 20.0%; p = 0.02). Eight (57.1%) patients with high CSO-EPVS degree had a positive florbetapir PET compared with 4 (16.7%) with low CSO-EPVS degree (p = 0.01). In contrast, prevalence of florbetapir PET positivity was similar between patients with high vs. low BG-EPVS. In multivariable analysis adjusted for age, hypertension, and MRI markers of CAA, florbetapir PET positivity (odds ratio (OR) 6.44, 95% confidence interval (CI) 1.32-38.93; p = 0.03) was independently associated with high CSO-EPVS degree. CONCLUSIONS: Among patients with spontaneous ICH, high degree of CSO-EPVS but not BG-EPVS is associated with amyloid PET positivity. The findings provide further evidence that CSO-EPVS are markers of vascular amyloid burden that may be useful in diagnosing CAA.

Effect of Red Light-Emitting Diodes Irradiation on Hemoglobin for Potential Hypertension Treatment Based on Confocal Micro-Raman Spectroscopy.

Red light-emitting diodes (LED) were used to irradiate the isolated hypertension hemoglobin (Hb) and Raman spectra difference was recorded using confocal micro-Raman spectroscopy. Differences were observed between the controlled and irradiated Hb by comparing the spectra records. The Raman spectrum at the 1399 cm-1 band decreased following prolonged LED irradiation. The intensity of the 1639 cm-1 band decreased dramatically in the first five minutes and then gradually increased in a time-dependent manner. This observation indicated that LED irradiation increased the ability of oxygen binding in Hb. The appearance of the heme aggregation band at 1399 cm-1, in addition to the oxygen marker band at 1639 cm-1, indicated that, in our study, 30 min of irradiation with 15.0 mW was suitable for inhibiting heme aggregation and enhancing the oxygen-carrying capacity of Hb. Principal component analysis showed a one-to-one relationship between irradiated Hb at different time points and the corresponding Raman spectra. Our approach could be used to analyze the hemoglobin from patients with confocal micro-Raman spectroscopy and is helpful for developing new nondrug hypertension therapy.

Association Between Elevated Pulse Pressure and High Resting Coronary Blood Flow Velocity in Patients With Angiographically Normal Epicardial Coronary Arteries.

BACKGROUND: The aim of our study was to evaluate the relationship of pulse pressure (PP), a raw index of arterial stiffness, with noninvasively determined coronary flow reserve (CFR) and its components, in patients with angiographically normal epicardial coronary arteries. METHODS AND RESULTS: The study population included 398 patients without angiographic evidence of coronary stenosis, who underwent high-dose dipyridamole stress echocardiography with transthoracic-derived CFR evaluation on the left anterior descending artery. CFR was calculated as the ratio between high-dose dipyridamole and resting coronary diastolic peak velocities. Patients were divided into 2 groups: the first group included the first and second PP tertiles (n=298, PP ≤60 mm Hg) and the second group included the highest PP tertile (n=100, PP >60 mm Hg). Mean blood pressure, systolic blood pressure (both P<0.0001), age (P<0.002), and left ventricular mass index (P=0.013) were higher in the highest PP tertile, which also showed higher resting coronary flow velocity (31.6±9.6 cm/s versus 27.7±6.4 cm/s, P<0.0001) and marginally lower CFR (2.5±0.6 versus 2.6±0.6, P=0.044). Hyperemic coronary flow velocity did not differ between the 2 groups. By separate multiple linear regression analyses, after adjusting for sex, age, the highest systolic blood pressure tertile (≥140 mm Hg), left ventricular mass index, and cardiovascular risk factors, the highest PP tertile was associated with resting coronary flow velocity (P=0.003) and only marginally with hyperemic coronary flow velocity (P<0.02), whereas its association with CFR was not significant. CONCLUSIONS: In patients without epicardial coronary artery stenosis, the highest PP tertile is associated with an increased coronary flow velocity at rest.

Hypotensive acute effect of photobiomodulation therapy on hypertensive rats.

The purpose of this study was to evaluate the acute effect of photobiomodulation therapy (PBM) on arterial pressure in hypertensive and normotensive rats with application in an abdominal region. Normotensive (2K) and hypertensive (2K-1C) wistar rats were treated with PBM. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after PBM application. The nitric oxide (NO) serum concentration was measured before and after PBM application. Vascular reactivity study was performed in isolated thoracic aortas. Aluminum gallium arsenide (GaAlAs) diode laser was used, at 660nm wavelength and 100mW optical output. The PBM application induced a decrease of SAP in 2K-1C rats. In 2K rats, the PBM application had no effect on SAP, DAP and MAP. Moreover, the magnitude of hypotensive effect was higher in 2K-1C than in 2K rats. The PBM application induced a decrease of HR in 2K-1C and 2K, with higher effect in 2K-1C rats. In 2K-1C, the hypotensive effect induced by PBM was longer than that obtained in 2K rats. PBM application induced an elevation of NO concentration in serum from 2K-1C and 2K rats, with higher effect in 2K-1C. In isolated aortic rings PBM effect is dependent of NO release, and is not dependent of nitric oxide synthase (NOS) activation. Our results indicate that the abdominal acute application of PBM at 660nm is able to induce a long lasting hypotensive effect in hypertensive rats and vasodilation by a NO dependent mechanism.

Long-term antihypertensive effects of far-infrared ray irradiated from wooden board in spontaneously hypertensive rats.

BACKGROUND: Far-infrared ray (FIR) has been widely used in promoting health and has been shown to exert beneficial effects in vascular function. The non-thermal effect of FIR has been found to play a significant role in the protective effect on some vascular-related diseases, but its protective effects and use against hypertension have not been clearly presented. METHODS: In the present study, by using a wooden board coated with FIR-irradiated materials, we evaluated the long-term antihypertensive effect on spontaneously hypertensive rats (SHRs) in the environment in contact with the FIR-irradiated wooden board. SHRs were placed on the wooden board with or without FIR radiation for 4 weeks. RESULTS: The systolic blood pressure (BP) of SHRs undergoing different treatments was measured weekly using a tail-cuff method. FIR radiation significantly reduced the systolic BP of the SHRs along with a decreasing plasma level of angiotensin II and an increasing plasma level of bradykinin. In addition, long-term contact of FIR did not significantly affect the BP in normotensive Wistar Kyoto rats (WKYs). CONCLUSIONS: Our results provided the evidence based on which FIR radiation could be considered an effective non-pharmacological choice for preventing hypertension.

Hemodynamic effect of laser therapy in spontaneously hypertensive rats.

Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

[Magnetic-laser influence on the system of nitric oxide and contractile activity of smooth muscles of rat aorta under hypertension].

The study was conducted on three groups of rats: Group I included Wistar rats with normal blood pressure (first control group); group II - rats with genetically determined hypertension (second control group); group Ill - rats with genetically determined hypertension under the influence ofmagnetic-laser power (study group). For the low-intensively magnetic-laser influence (MLI) we have used device MIT-MT, Ukraine, which was designed for the treatment of low-frequency magnetic field using optical flow blue and red ranges of spectrum. The MLI duration was 15 minutes for the blue range, and 25 minutes for the red one. Biochemical studies included the determination of the activity of isoenzymes of NO-synthase: constitutive (cNOS) and inducible (iNOS), the content of free hemoglobin, stable metabolites of NO, namely nitrite - (NO2(-)) and nitrate - (NO3(-)) anions, resistance to acid hemolysis of red blood cells. The contractile activity of smooth muscles of the aorta was measured. We found that magnetic-laser exposure of rats with genetically determined hypertension in the red (630 nm) and blue (470 nm wavelength) optical range even after a single session leads to an increased synthesis of nitric oxide in the blood plasma. Our data sindicate that the most effective in the intensification of endogenous nitric oxide (increase of NO2(-) and reduction of NO3(-)) and endothelium-dependent responses of aorta in rats with genetically determined hypertension was a ten-day course of the magnetic-laser exposure in the optical flow of the blue spectral range. Also, after 10 sessions of magnetic-laser exposure in rats from the above specified spectrum a stabilization of erythrocyte membranes was observed.

[Combined application of magnetolaserotherapy and polyunsaturated fatty acids for the treatment of patients with hypertensive disease].

The authors report the results of combined treatment including application of magnetolaserotherapy and n-3 polyunsaturated fatty acids for the management of patients presenting with hypertensive disease. These data give evidence of the accumulation of atherogenic fractions of plasma lipids and pathological modification of the fatty acid composition in erythrocyte membranes. They suggest the appropriateness of lipid-correcting and membrane-protective treatment for patients presenting with hypertensive disease. It is concluded that the proposed combination of magnetolaserotherapy and polyunsaturated fatty acids may be instrumental in the normalization of the serum lipid profile and the correction of the cellular fatty acid composition.

[Potentials of combined non-medication therapy of arterial hypertension associated with ischemic heart disease].

The objective of the present work was to develop methods and a scientifically sound rationale for the optimization of clinical results of the treatment of patients presenting with arterial hypertension (AH) associated with coronary heart disease (CHD) using red and infra-red (IR) low-intensity laser irradiation. The study included a total of 90 patients of working age (62.2% of men and 37.8% of women) having AH associated with coronary heart disease and abnormal blood lipid spectrum. They were allocated to three groups each comprising 30 patients matched for age, sex, severity of clinical conditions, and character of maintenance medicamental therapy. Patients of group 1 were treated by intravenous blood irradiation with laser light; those in group 2 were given similar treatment in combination with external low-intensity IR laser therapy; patients of group 3 received basal medicamental therapy. The study allowed the clinical value of different variants of low-intensity laser therapy to be assessed as regards efficiency of correction of hypersympaticotony, disturbances of lipid metabolism, and refractoriness to pharmaceutical products as well as improved tolerance of physical exercises, anti-hypertensive, anti-ischemic, and anti-anginal effects, diastolic function, and quality of life as targets of the comprehensive rehabilitative program designed for patients with AH associated with coronary heart disease. An optimized therapeutic modality is proposed for patients presenting with these pathologies based on the application of the low-intensity laser irradiation regime characterized by mutual amplification and complementary action of red and infrared lights.

[Effect of intravenous laser blood irradiation on endothelial dysfunction in patients with hypertensive disease].

The aim of this work was to study effect of intravenous laser blood irradiation (ILBI) on endothelial dysfunction in 120 patients (mean age 53.4 +/- 1.3 yr) with grade I-II hypertensive disease (HD) allocated to 2 groups. Traditional drug therapy given to patients of control group was supplemented by ILBI using a Mulat laser therapy device in the study group. Endothelial function was evaluated from the total plasma concentration of stable NOx metabolites, nitrates (NO3-), nitrites (NO2-), and Willebrand's factor. HD patients were found to have elevated activity of the Willebrand factor and show 3 types of response of the NO generating system: (1) decreased NO synthesis, (2) lack of its changes, and (3) increased NO synthesis. NO production in HD patients negatively correlated with systolic (r = -0.59) and diastolic (r = - 0.64) arterial pressure (AP) which suggests the relationship between decreased NO production and elevated AP. Inclusion of ILBl in the therapy of HD resulted in a significant decrease of Willebrand's factor activity and normalization of the NO level regardless of its initial value.

Fewer mega-trials and more clinically oriented studies in hypertension research? The case of blocking the renin-angiotensin-aldosterone system.

In recent years, medical practice has been influenced substantially by several factors, including the overwhelming development of evidence-based medicine, which is a consequence of the impressive, growing number of large clinical trials, the so-called "mega-trials." These clinical studies are designed mostly to investigate the effects of drugs or treatments on hard end points that cannot be tested by individual physicians in their daily clinical practice. The growing role of this epidemiologic approach to medicine, which is based mostly on the assessment of the average response or behavior of large populations rather than of individuals, is systematically replacing the former knowledge and reference points of the physician, as a substitute rather than as an aid. Taking into account the case of hypertension and particularly the renin-angiotensin system-blocking agents, this article reviews the issues and limitations of transferring evidence from mega-trials to clinical practice and suggests new strategies to make trials more effective and transferable to the case of individual patients.

[Metabolic determinants of efficacy of infrared laser therapy in hypertensive patients with combined pathology].

By a distinct pathogenetic direction of a therapeutic action of laser therapy (LT) on different regulators of blood pressure (BP) and metabolism, 109 patients with essential hypertension (EH) and atherosclerosis and/or diabetes mellitus were studied for LT efficacy depending on metabolis disorders. LT demonstrated metabolic neutrality and unefficacy in patients with multiple marked disorders of fat metabolism and hyperglycemia. Metabolic factors determining LT efficacy comprise hypercholesterinemia, hypertriglyceridemia and hyperglycemia. The factorial analysis points to essential factor restructuring in metabolic disorders. The obtained equation of multiple regression allows prognostication of the degree of a fall of mean BP in response to LT depending on the degree of metabolic disorders.

[Impulse low-intensity electromagnetic field in the treatment of adolescents with essential arterial hypertension].

Effectiveness of different regimes of a course exposure to impulse low-intensity electromagnetic field (Infita unit) was studied in 69 adolescents with essential hypertension. A ten-day course of single 9 min procedures with 30 Hz field produced better antihypertensive effects than the regime used in the adults. This treatment provided improvement in bioelectric activity of the brain, mental state, central hemodynamics.

[Laser-, ultraphono-, and acupuncture in complex treatment of patients with hypertension]. / Lazero-, ul'trafono- i akupunktura v kompleksnom lechenii bol'nykh gipertonicheskoi bolezn'iu.

368 patients with hypertensive disease stage I and II were examined and treated either with laser puncture or acupuncture. Laser puncture was effective at stage I of hypertensive disease while acupuncture had a more potent hypotensive effect and can be used both in hypertensive disease stage I and II. Action on the acupuncture points and zones normalizes also parameters of the central and peripheral hemodynamics in hypertensive patients.