A single treatment,using Far Infrared light improves blood flow conditions in arteriovenous fistula

Abstract

BACKGROUND: A native arteriovenous fistula (AVF) is recommended for angio access in patients on chronic hemodialysis (HD). Fistula patency has been improved by exposure to Far Infrared light (FIR).

OBJECTIVE: To investigate whether a single FIR treatment could alter blood velocity, AVF diameter or inflammatory markers.

METHODS: Thirty patients with a native AVF in the forearm were included. Each patient was his/her own control. Ultrasound (US) examinations were performed before and after a single FIR treatment.

RESULTS: A single FIR treatment resulted in a significant increase in blood velocity over the AV fistula from a mean of 2.1 ± 1.0 m/s to 2.3 ± 1.0 m/s (p = 0.02). The diameter of the arterialized vein became wider; 0,72 cm ± 0.02 to 0,80 cm ± 0.02, (p = 0.006). The increase in fistula blood velocity correlated positively with base line serum- urate p = 0.004) and the increase in venous diameter with the base line plasma orosomucoid concentration (p = 0.005).

CONCLUSIONS: This study shows that a single FIR treatment significantly increased AVF blood velocity and vein diameter. Thus, one FIR treatment can help maturation of AVF in the early postoperative course.

Keywords

Ultrasound vascular access Far Infrared therapy hemodialysis

1 Introduction

Patients in hemodialysis are often the elderly or, chronically ill with significant comorbidity that, includes hypertension, diabetes and inflammation, all of which affect the quality of life. For optimal dialysis treatment, patients are dependent on a reliable access to the bloodstream, preferably via a native arteriovenous fistula (AVF) located in the forearm [1]. The most common complications in using such access are stenosis and thrombosis due to impaired blood flow mechanisms and anatomic factors [2 –4]. Another risk factor is the presence of increased blood pressure [5]. While some studies found no benefits using anticoagulants, antihypertensive medication, fish oil, immunosuppressive agents, radiation and synthetic grafts [6 –8], other studies that employed antihypertensive and antiplatelet medication have shown a small benefit [9, 10]. One year primary patency differs between 41% and 74% [11 –13]. In some recent studies, mainly from Taiwan, repeated Far Infrared light (FIR) treatment of the AVF improved patency and reduced the risk of complications [14 –16]. FIR light is an invisible, non-ionizing radiation emitted when a molecule de-excites from a higher quantum level and therefore expresses heat. FIR is part of the natural light spectrum of sunlight and heats objects by a process called direct light conversion and is perceived as heat by thermo-receptors in the surrounding skin. The invisible electromagnetic wave, with a spectrum between 4 and 1000 μm, is divided into three wavelengths -; short, medium and far infrared spectrum. The FIR device emits light in a spectrum between 3 and 25 μm. Exposure to this light leads to thermal and non-thermal effects on the AVF, and some patients experience a warm sensation. Some studies have shown a positive effect of such treatment on the inflammatory and immunogenic responses in rat tissue and in human cells [17 –19]. Repeated exposure with FIR over the AVF has improved the patency of newly-created AV fistulas before commencing regular treatment with hemodialysis [16]. FIR during a follow up period repeatedly after intervention of obstruction of AVF also led to a longer angioplasty-free period. No side effects were reported by FIR [20].

The aim of this study was to investigate whether a single Far Infrared light treatment could alter blood flow velocity and AVF diameter.

2 Material and methods

Forty-five patients over 18 years of age, with a native AVF, were informed of the study and asked to participate. Eleven patients refused and another four did not fulfill the criteria for inclusion: two because of non-functioning fistula, one because of personal reasons, and one because on-going infection. All subjects gave their written and oral informed consent. The study was approved by the Regional Ethical Review Board in Gothenburg, Sweden. Ethical committee number 424-13, approved July 24, 2013.

Thirty patients with a native end- to- side AVF localized in the forearm were included and their data are shown in Table 1. Fourteen patients had regular hemodialysis. Besides having an AVF, two patients at the time were treated by peritoneal dialysis and 14 were not yet on regular dialysis. The 20 patients treated with Erythropoiesis Stimulating Agents (ESA) received a mean dose of 4350 Units/week. None of the patients in the study had fever or was treated with any antibiotics.

Table 1
Patient data

Variables Data, mean value,±SD

Number of patients 30

Male/female ratio 17/13

Age, years 59.9±14.2

Diabetes (yes/no) 12/18

BMI 27.6±5.5

Statin treatment (yes/no) 12/18

Anticoagulation treatment (yes/no) 8/22

ESA treatment (yes/no) 20/10

Uric acid lowering drug (yes/no) 3/27

Duration of AVF, months 59.9±42.3

Hemoglobin, g/L latest 119±15.5

Variables	Data, mean value,±SD
Number of patients	30
Male/female ratio	17/13
Age, years	59.9±14.2
Diabetes (yes/no)	12/18
BMI	27.6±5.5
Statin treatment (yes/no)	12/18
Anticoagulation treatment (yes/no)	8/22
ESA treatment (yes/no)	20/10
Uric acid lowering drug (yes/no)	3/27
Duration of AVF, months	59.9±42.3
Hemoglobin, g/L latest	119±15.5

The design of the study was based on the principle of case-control, where the patient was his/her own control. This design also excludes inter- individual errors.

Ultrasound (US) investigations were performed before and after FIR treatment.

The AVF was examined with Doppler ultrasound, (ACUSON, SEQUOIA 512, with color Doppler 6 L3, Mountain View, CA, USA) before and after one single 40 minutes treatment with FIR. FIR was performed using a wide spectrum Far-Infrared Therapy Unit (model TY 102N, WS Far Infrared Medical Technology Co., Ltd., Taipei County 231 Taiwan). Before the first US investigation systolic and diastolic blood pressure (BP) was measured with a manometer (MAXNIBP, CAS 740-1, CAS Medical systems Inc., Branford, CT,USA), followed by blood-sampling, for serum-proteins, LDL-cholesterol and urate from the non-fistula arm. The most recent blood hemoglobin level was also recorded.

The US measurements were performed with the patient in a supine position and the area of the AV fistula was investigated with US from the wrist up to the veins at the distal part of the upper arm. Three measure points were localized and marked: the first over the feeding artery, the second over the fistula area, and the third point over the arterialized vein (distal part of the AVF localized towards the heart; here denominated vein). The points were selected as follows; the transducer was placed over the AVF where the typical flow curve, audible thrill and the feature of the vessel in the area of anastomosis (artery, fistula and vein with measurable blood flow) could be localized. This was repeated to ascertain the relevant point to optimize the sampling. Diameter and flow measurements were performed twice if data were congruent, three times otherwise, over each of the three points. Flow velocity data were recorded in a special protocol. After the US investigation, treatment with FIR was performed for 40 minutes over the area comprising the three marked points, at a distance of 25 centimeters above the skin surface. Directly after FIR treatment, new blood sampling was performed and blood pressure was measured. US investigation of the AVF was again repeated prior to the FIR treatment. Data were collected of the patient’s age, gender, diagnosis, inflammatory status, type of AVF, vintage, ongoing infection, smoking habits, metabolic status, blood pressure, MAP (Mean Arterial Pressure) and BMI (Body Mass Index). Current medication, including anticoagulants and weekly doses of ESA and uremic status; (transplant, type of dialysis or not yet start of dialysis) were also noted. The blood samples were sent to the laboratory, UNILABS (accredited) and were analyzed according to established routines.

Statistical analyses were performed using SPSS software version 19 (IBM, Inc. Chicago, Illinois, USA). Values in this study were expressed in median or mean and standard deviation unless otherwise stated. The mean blood flow velocity at each point (m/s) was calculated based on the mean value of at least two measurements. The results of blood samples were based on 29 patients since one patient did not fulfill the blood testing requirements. If an effect would be found in at least 30% of patients the power of the paired study was predicted to be higher than 80%. Student’s paired t-test was used with the patient acting as his/her own control. For group comparison the Mann Whitney test was used. Bivariate correlation analyses were performed using Spearman rank correlation (r_o test). A two-tailed p-value of less than 0.05 was considered to be statistically significant.

3 Results

One session of FIR exposure for 40 minutes resulted in a significant increase in blood -velocity over the fistula from a mean of 2.1 m/s (±1.0) to 2.3 m/s (±1.0, p = 0.02). There was no significant increase in arterial (1.71 m/s to 1.78 m/s) or venous blood velocity (0.87 m/s to 0.93 m/s, p = 0.056). The venous diameter increased significantly from 0,72 cm (±0.2) to 0,80 cm (±0.2, p = 0.006). There was no significant change in diameter of the artery or fistula (Table 2).

Table 2
Change in variables before and after FIR in 30 patients (given as mean ± SD and P value)

Variable Mean ±SD P =

Fistula flow velocity – start, m/s 2.11 1.00

Fistula flow velocity – end, m/s 2.28 1.01 0.022

Arterial flow velocity – start, m/s 1.71 0.80

Arterial flow velocity – end, m/s 1.78 0.86 ns

Venous flow velocity – start, m/s 0.87 0.44

Venous flow velocity – end, m/s 0.93 0.46 0.056

Fistula diameter – start, cm 0.84 0.47

Fistula diameter – end, cm 0.84 0.49 ns

Arterial diameter – start, cm 0.51 0.15

Arterial diameter – end, cm 0.49 0.13 ns

Venous diameter – start, cm 0.72 0.20

Venous diameter – end, cm 0.80 0.20 0.006

BP syst – start, mmHg 133 25

BP syst – end, mmHg 131 26 ns

BP diast – start, mmHg 74 17

BP diast – end, mmHg 75 14 ns

MAP – start, mmHg 93 16

MAP – end, mmHg 94 16 ns

Heart rate – start, beats/min 72 9.8

Heart rate – end, beats/min 68 9.4 0.043

LDL – start, mmol/L^a 2.33 1.20

LDL – end, mmol/L 2.28 1.10 ns

Urate – start, mmol/L^a 347 181

Urate – end, mmol/L 358 166 ns

Orosomucoid – start, mg/L^a 1.11 0.3

Orosomucoid – end, mg/L 1.08 0.3 ns

Variable	Mean	±SD	P =
Fistula flow velocity – start, m/s	2.11	1.00
Fistula flow velocity – end, m/s	2.28	1.01	0.022
Arterial flow velocity – start, m/s	1.71	0.80
Arterial flow velocity – end, m/s	1.78	0.86	ns
Venous flow velocity – start, m/s	0.87	0.44
Venous flow velocity – end, m/s	0.93	0.46	0.056
Fistula diameter – start, cm	0.84	0.47
Fistula diameter – end, cm	0.84	0.49	ns
Arterial diameter – start, cm	0.51	0.15
Arterial diameter – end, cm	0.49	0.13	ns
Venous diameter – start, cm	0.72	0.20
Venous diameter – end, cm	0.80	0.20	0.006
BP syst – start, mmHg	133	25
BP syst – end, mmHg	131	26	ns
BP diast – start, mmHg	74	17
BP diast – end, mmHg	75	14	ns
MAP – start, mmHg	93	16
MAP – end, mmHg	94	16	ns
Heart rate – start, beats/min	72	9.8
Heart rate – end, beats/min	68	9.4	0.043
LDL – start, mmol/L^a	2.33	1.20
LDL – end, mmol/L	2.28	1.10	ns
Urate – start, mmol/L^a	347	181
Urate – end, mmol/L	358	166	ns
Orosomucoid – start, mg/L^a	1.11	0.3
Orosomucoid – end, mg/L	1.08	0.3	ns

BP = blood pressure; MAP = mean arterial pressure; ^a = based on data from 29 patients.

The change in blood velocity or diameter of the arterial, fistula or venous part of the AVF did not differ between patients with or without diabetes mellitus, those who were or were not receiving hemodialysis, statins or anticoagulants or between men and women.

After FIR, the heart rate decreased (mean 72±9.8 beats/min to 68±9.4, p = 0.043) and LDL-cholesterol was reduced (mean 2.33 mmol/L±1.2 versus 2.28 mmol/L±1.10, p = 0.091) while there was no change in systolic or diastolic blood pressure, mean arterial pressure, serum- orosomucoid (ORM) or serum-urate.

The increase in fistula blood velocity after FIR correlated positively with base line serum-urate (r_o = 0.52, p = 0.004) and the increase in venous diameter correlated with the base line ORM levels (r_o = 0.51, p = 0.005). There was no correlation between AVF blood velocity change after FIR to age, blood hemoglobin, dose of ESA, baseline systolic or diastolic BP, MAP or LDL- cholesterol.

The paired Student T test was not significant for resistance index (RI). All patients had a patent AVF during the follow up period of 30 days. There was no side effect experienced by FIR. Some patients, but not all, noticed a sensation of ‘warming up of the area’ during the FIR treatment. This sensation lasted for a limited time and disappeared before the second ultrasound examination was performed.

4 Discussion

The present study for the first time clarifies, by US examination, that already one single procedure of FIR causes both immediate improvements in AVF blood flow velocity as well as an increase in the venous diameter of the AVF. The diameter of the artery or the fistula did not change significantly. This difference may be due to that FIR increases skin temperature and affects tissue to a depth of approximately twenty mm [19 , 22]. FIR therefore affects the vein diameter more significant, since the venous part of the AVF lies more superficially, and has a thinner muscular wall, than the artery and the fistula. FIR may even have a local effect on thermo-receptors and the autonomous innervation of the vessel wall, which can affect the vessel diameter. This could also indicate a relaxation of the sympathetic nervous system induced by FIR. Some patients experienced a warm sensation, but there was no correlation with diabetes or neuropathy. The duration of the effect of FIR is not clarified, However, findings from one animal study by Yu et al. showed an increased skin microcirculation persisting for 60 minutes after FIR treatment, suggesting also a non-thermic biologic effect [19].

Long-term data showed that FIR treatment three times weekly for a year was beneficial for AVF blood flow and patency [14–16 , 20]. The question therefore arose, and is one that has to be clarified by further studies, as to how many treatments and the duration of each session, are needed to achieve and maintain good fistula function. Lin et al. showed that one FIR caused an increased AVF flow during one hemodialysis treatment, measured with Transonic^®, used as a dilution volume method [14]. Whether this was due to a change in cardiac output or blood pressure was not clarified.

Beneficial effects of FIR may counteract some of the negative factors with which an AVF is associated including the formation of a stenosis, and with upstream factors such as shear stress, surgical trauma and repeated vessel puncture. Downstream factors include intimal hyperplasia, accumulation of extracellular matrix, oxidative stress and proliferation of smooth muscle cells with migration to intima [23, 24]. Cellular models by Stracke have shown the influence of TGF-β (Transforming Growth Factor) and IgF-1 in the forming of a stenotic lesion on the venous side of the AVF [25]. In the present study the beneficial response to FIR was better if the patient had a higher baseline serum-urate or ORM. High serum-urate is not only a marker for uremia but also a marker of cardiovascular disease (CVD), involved in oxidative stress and inducing pro-inflammatory effects [26 –28]. Also ORM is an acute phase reactant for inflammation. This may indicate that patients with inflammation and CVD are more likely to respond to FIR. It is notable that FIR has been reported to have a beneficial effect on inflammatory mediators. In the study by Toyokawa there was a positive effect of FIR on wound healing in rats, as measured by the number of fibroblasts and amount of collagen when treated repeatedly for 14 days [17]. Hemeoxygenase-1(HO-1) is a stress protein (heat shock protein-HSP) that mediates vasoprotective actions in the circulation. Some studies indicate that the effect of FIR may up-regulate factors, such as HO-1, and the L-arginine/nitric oxide pathway, in the cascade of components remodeling the vessel intima and media that counteract the growth of smooth muscle cells [15 , 29].

In the present study there was no significant change in ORM before and after FIR. However, even if a change would occur locally the marker is rapidly diluted by the total blood volume of the body. The small reduction of LDL-cholesterol after FIR may be due to a prolonged period of fasting.

The limitation of this study is the large variation of the vintage of the AVF’s. However, data can also be interpreted that despite the variation in vintage and study population, there was a significant effect achieved already after one exposure to FIR. Other limitations of the study were the non-blinded design and relatively small number of patients.

In conclusion, this study shows that already one episode of 40 minutes exposure to Far Infrared light exerts an immediate beneficial effect on blood flow velocity and venous diameter in the AVF area. Patients with a higher level of serum-urate and ORM may respond better. Repeated FIR treatments may be needed in selective AVF to achieve long-term patency and early post-operative after surgery where flow is limited. These data indicate that FIR may be an additional tool in attempts to prevent complications and re-interventions of the AVF. Further studies will clarify for how long time repeated exposure is necessary to optimize patency.

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