Research Papers

Prognostic Factors Influencing the Patency of Hemodialysis Vascular Access: Literature Review and Novel Therapeutic Modality by Far Infrared Therapy

Lin CC, Yang WC. J Chin Med Assoc. 2009 Mar;72(3):109-16.

Abstract:

In Taiwan, more than 85% of patients with end-stage renal disease undergo maintenance hemodialysis (HD). The native arteriovenous fistula (AVF) accounts for a prevalence of more than 80% of the vascular access in our patients. Some mechanical factors may affect the patency of hemodialysis vascular access, such as surgical skill, puncture technique and shear stress on the vascular endothelium. Several medical factors have also been identified to be associated with vascular access prognosis in HD patients, including stasis, hypercoagulability, endothelial cell injury, medications, red cell mass and genotype polymorphisms of transforming growth factor - ƒÀ1 and methylene tetrahydrofolate reductase. According to our previous study, AVF failure was associated with a longer dinucleotide (GT)n repeat (n . 30) in the promoter of the heme oxygenase-1 (HO-1) gene. Our recent study also demonstrated that far-infrared therapy, a noninvasive and convenient therapeutic modality, can improve access flow, inflammatory status and survival of the AVF in HD patients through both its thermal and non-thermal (endothelial-improving, anti-inflammatory, antiproliferative, antioxidative) effects by upregulating NF-E2-related factor-2-dependent HO-1 expression, leading to the inhibition of expression of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1.

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Far-Infrared Therapy: A Novel Treatment to Improve Access Blood Flow and Unassisted Patency of Arteriovenous Fistula in Hemodialysis Patients

Lin CC, Chang CF, Lai MY, Chen TW, Lee PC, Yang WC. J Am Soc Nephrol. 2007 Mar;18(3):985-92.

Abstract:

Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD02 monitor during HD. The Qa1/Qa2 and Qa3/Qa4 were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 ± 114.7 versus -33.4 ± 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Δ(Qa4 - Qa3) (36.2 ± 82.4 versus -12.7 ± 153.6 ml/min; P = 0.027), Δ(Qa3 - Qa1) (36.3 ± 166.2 versus -51.7 ± 283.1 ml/min; P = 0.035), Δ(Qa4 - Qa2) (99.2 ± 144.4 versus -47.5 ± 244.5 ml/min; P < 0.001), and Δ(Qa4 - Qa2) -Δ (Qa3 - Qa1) (62.9 ± 111.6 versus 4.1 ± 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01).

In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.

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Far Infrared Therapy Inhibits Vascular Endothelial Inflammation via the Induction of Heme Oxygenase-1

Lin CC, Liu XM, Peyton K, Wang H, Yang WC, Lin SJ, Durante W. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):739-45.

Abstract:


Objective— Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation.


Methods and Results
— Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-.–mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis.


Conclusions
— These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.

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Far-Infrared Mitigates Vascular Endothelial Growth Factor-Induced Proliferation in Human Umbilical Vein Endothelial Cells Via the Generation of Nitric Oxide and Reactive Oxygen Species

(Poster of Annual meeting of ASN 2008)

Yung-Ho Hsu, Tso-Hsiao Chen, Chun-Cheng Hou, Yuh-Mou Sue, Cheng-Hsien Chen

Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan


Vascular access dysfunction causes enormous clinical morbidity in hemodialysis patients. Venous stenosis as a result of neointimal hyperplasia is the major cause of it. Far-infrared (FIR) therapy has been reported recently as a competent therapeutic modality in improving access flow and patency of the arteriovenous fistula. But the exact mechanism remains to be determined. The present study aims to evaluate the influence of FIR on vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVEC) and examine the mechanisms. VEGF-induced proliferation of HUVEC was significantly reduced by FIR at 20 mili watt (mw)/cm2 for 30min in comparison with those without FIR radiation. The VEGF-induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in HUVEC was also inhibited by FIR. These effects were not obvious by the thermal effect in HUVEC alone from 37.5 to 38oC, as the FIR treatment increased the cultured medium temperature approximately 0.5oC. We found FIR treatment induced the phosphorylation of endothelial nitric oxide synthase (eNOS) and increased nitric oxide (NO) in HUVEC. The NOS inhibitor N G -nitro-l-arginine methylester (L-NAME) abolished the inhibitory effects of FIR on cell proliferation and the phosphorylation of ERK1/2. FIR also induced reactive oxygen species (ROS) generation in HUVEC. The NADH oxidase inhibitors and ROS scavengers blocked the inhibitory effect of FIR on cell proliferation, and significantly reduced FIR-induced eNOS phosphorylation. We also found that Src homology 2- containing tyrosine phosphatase (SHP-2) was associated with phospho-eNOS and transiently oxidized to inhibit the dephosphorylation of phosphor-eNOS during FIR treatment. These data suggest that FIR, through its nonthermal effects, induces NO and ROS generation to mitigate VEGF-induced proliferation in HUVEC.


Physical Examination of Limb Vessels for Native Arteriovenous Shunt Construction under Low-Density Far Infrared-ray Irradiation over Hands

Jih-Chung Chiang, Hung-Sheng Wu, Ming-He Huang

Department of Cardiovascular Surgery Show Chwan Memorial Hospital

Purpose:
To control quality of native arteriovenous (AV) shunt construction over upper limbs for long term hemodialysis (HD)

Background: Since 1966 Dr. Brescia Cimino et al created AV shunt on the forearm for long term HD, native AV shunt becomes gold standard access for HD due to its longevity and less complication. Physiologically, limb vessels have important function in heat dissipation, so it may be helpful to dilate the vessels with far infrared-ray (FIR) irradiation during physical examination.

Materials and methods: Since June 2001, all patients suffered from end stage renal disease need AV shunt construction or revisions were enrolled in this study. A low-density far-infrared emitter with wavelength of 3-25 μm was used to irradiate both hands during history taking and physical examination. Irradiation duration ranged from 5 minutes to about 20 minutes. Palpation of pulsation of brachial, radial and ulnar arteries and Allen test was done to rule out severe atherosclerotic occlusion of the artery. Palpation of the vein to make sure of its size (about 3 mm) and elasticity was suitable for shunt construction. During operation the inner lumen size of the vein selected for shunt construction was measured with vessel dilators. Temperature of the hand skin is not elevated above 34oC. If severe dehydration of the patient is impressed, oral intake of 100-200 ml warm water was institute immediately. Then, the irradiation procedure was repeated. In case of failing AV shunt, degree of thrill before irradiation was compared with during irradiation to differentiate fixed stenosis with temporarily spastic stenosis of the shunt vessels.

Results:
More then 5000-access operations‘ decision-makings we had been made in five years. About one third of the operation procedures were native AV shunt construction, the vein size was almost same as that measured physically before operation. More then 50 patient’s original native AV shunts were rescued with FIR irradiation without shunt revision. At least 10 more patients had experience of repeated graft bridged AV shunt failure were changed to native AV shunt. And 5 primarily constructed shunts were needled to delivery HD in one week.

Conclusion:
Physical examination of limb vessels for native arteriovenous shunt construction under low-density far infrared-ray irradiation over hands does improve decision-making quality of access operation.


Biological Effect of Far-Infrared Therapy on
Increasing Skin Microcirculation in Rats
Yu SY, Chiu JH, Yang SD, Hsu YC, Lui WY, Wu CW. Photodermatol Photoimmunol Photomed.
2006 Apr;22(2):78-86.

Background/purpose:

Insufficient microcirculation of skin leads to acute and chronic tissue ischemia in cases of trauma, reconstructive surgery, diabetes mellitus and peripheral arterial occlusive disease. The autonomic nervous system and nitric oxide (NO) play important roles in maintaining blood perfusion of the skin. Far-infrared (FIR) therapy provides low energy of light emitted from an artificial radiator and has been used to treat many vascular-related disorders. Nevertheless, the mechanisms through which FIR works remain unclear. The present study aims to test the hypothesis that the effect of FIR is through increasing skin microcirculation by a mechanism other than its thermal effect.

Methods:

Sixty rats were used in the present study. A WS TY301 FIR emitter was placed 20 cm above the rats. Skin temperature and blood flow were continuously measured by a K-type thermocouple. Under laboratory control, the abdominal skin temperature steadily increased from 38–39 1C, and was kept at constant temperature. Skin microcirculation was measured with a continuous laser Doppler flowmeter .

Results:

There was no significant change of skin blood flow during FIR treatment. Skin blood flow increased significantly soon after the removal of the FIR emitter. The stimulating effect on skin blood flow was more significant in the rats treated with FIR for 45 min and could be sustained as long as 60 min. These findings suggested a non- thermic biological effect of FIR on skin microcirculation. The promotive effect of FIR on increasing skin blood flow was not influenced by pretreatment of APP (atropine, propranolol and phentolamine ), but was suppressed by pretreatment with NG-nitro-L- arginine methyl ester (an endothelial nitric oxide synthase inhibitor).

Conclusion:

In conclusion, FIR therapy exerts a NO-related biological effect to increase skin microcirculation in rats. This might bring into perspective the clinical application of FIR to treat ischemic disease by augmenting L- arginine /NO pathway.

 



Far infrared radiation (FIR): its biological effects and medical applications
Fatma Vatansever and Michael R. Hamblin. Photonics Lasers Med. 2012 Nov 1; 4: 255–266

Abstract

Far infrared (FIR) radiation (lambda = 3-100 mcm) is a subdivision of the electromagnetic spectrum that has been investigated for biological effects. The goal of this review is to cover the use of a further sub-division (3– 12 mcm) of this waveband, that has been observed in both in vitro and in vivo studies, to stimulate cells and tissue, and is considered a promising treatment modality for certain medical conditions. Technological advances have provided new techniques for delivering FIR radiation to the human body. Specialty lamps and saunas, delivering pure FIR radiation (eliminating completely the near and mid infrared bands), have became safe, effective, and widely used sources to generate therapeutic effects. Fibers impregnated with FIR emitting ceramic nanoparticles and woven into fabrics, are being used as garments and wraps to generate FIR radiation, and attain health benefits from its effects.



Effect of far infrared therapy on arteriovenous fistula maturation:
an open-label randomized controlled trial.
Lin CC, Yang WC, Chen MC, Liu WS, Yang CY, Lee PC. Am J Kidney Dis. 2013 Aug;62(2):304-11

Abstract
BACKGROUND:

Malfunction of the arteriovenous fistula (AVF) is an important cause of morbidity and hospitalization in hemodialysis (HD) patients. The aim of this study is to evaluate the effect of far infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5.

STUDY DESIGN:
Randomized controlled study.

SETTING & PARTICIPANTS:

Patients with estimated glomerular filtration rate of 5-20 mL/min/1.73 m².

INTERVENTION:

40 minutes of far infrared therapy 3 times weekly for a year.

OUTCOMES:
The primary outcome is the rate of AVF malfunction within 12 months, with malfunction defined as either: (1) thrombosis without thrill for AVFs not undergoing HD or (2) receiving any type of interventional procedure due to a lower Kt/V (<1.2) for patients undergoing HD. Secondary outcomes include: (1) cumulative primary unassisted AVF patency, defined as time from creation of the AVF to the first episode of AVF malfunction; (2) physiologic maturation of the AVF by the definition of AVF access blood flow (Qa) =>500 mL/min and AVF diameter =>4 mm at 3 months; and (3) clinical maturation of the AVF suitable for HD at 1 year.

MEASUREMENTS:
AVF Qa was measured by Doppler ultrasonography at 2 days and 1, 2, 3, and 12 months.

RESULTS:

We enrolled 122 patients who were randomly allocated to the intervention (n = 60) and control (n = 62) groups. In comparison to controls, patients in the intervention group had higher Qa values at 1, 2, 3, and 12 months; a higher rate of physiologic maturation (90% vs 76%; P = 0.04) at 3 months; and a lower rate of AVF malfunction (12% vs 29%; P = 0.02) but higher rates of AVF cumulative unassisted patency (87% vs 70%; P = 0.01) and clinical maturation (82% vs 60%; P = 0.008) within 12 months.

LIMITATIONS:

This is a single-center nonblinded study.

CONCLUSIONS:

Far infrared therapy improves the access flow, maturation, and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5.




Length polymorphisms of heme oxygenase-1 determine the effect of far-infrared therapy on the function of arteriovenous fistula in hemodialysis patients: a novel physicogenomic study.
Lin CC1, Chung MY, Yang WC, Lin SJ, Lee PC. Nephrol Dial Transplant. 2013 May;28(5):1284-93.

Abstract
BACKGROUND:
The objective of this study was to evaluate the interaction between the length polymorphism of the guanosine thymidine repeat [(GT)n] in the heme oxygenase-1 (HO-1) gene and far-infrared (FIR) therapy on access flow (Qa) and arteriovenous fistula (AVF) patency in hemodialysis (HD) patients.

METHODS:
A total of 280 HD patients were randomized into a control group (n = 141) and the FIR group (n = 139) who received 40 min of FIR therapy three times weekly for a year during the study period from May 2005 to December 2007. Access flow was measured during HD. The [(GT)n] was determined with the definition of long (L) allele as [(GT)n] ? 30 and short (S) allele as [(GT)n] < 30.

RESULTS:
The Qa decreased from S/S to S/L and further to the L/L group but increased by FIR therapy with the highest Qa increase in the S/S group. The incidence of AVF malfunction decreased both from the L/L, S/L to S/S group (32.4 versus 17.2 versus 10.9%, P = 0.007) and from the control group to FIR group (27.5 versus 12.6%, P = 0.004). Significant associations were found between AVF malfunction and the following factors (hazard ratio, P-value): a past history of AVF malfunction (2.45, P = 0.044), FIR therapy (0.369, P = 0.03) and L/L genotypes of HO-1 (2.531 versus S/S + S/L genotypes). The 1-year unassisted patency decreased from 91.9 and 77.6% in S/S and S/L subgroups with and without FIR therapy to 75.8 and 60% for L/L subgroup with and without FIR therapy, respectively (P < 0.001).

CONCLUSIONS:
FIR therapy improves Qa and patency of AVF in HD patients, with the best protective effect in those with S/S genotype of HO-1.



Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free hemodialysis access patency of recurrent obstructive lesions.
Lai CC, Fang HC, Mar GY, Liou JC, Tseng CJ, Liu CP. Eur J Vasc Endovasc Surg. 2013 Dec;46(6):726-32.

Abstract
OBJECTIVE:

To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA).

METHODS:
This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached.

RESULTS:
Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02).

CONCLUSIONS:
This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA.



Role of far infra-red therapy in dialysis arterio-venous fistula maturation and survival: systematic review and meta-analysis.
Bashar K, Healy D, Browne LD, Kheirelseid EA, Walsh MT, Clarke-Moloney M, Burke PE, Kavanagh EG, Walsh SR. . PLoS One. 2014 Aug 12;9(8):e104931

Abstract
INTRODUCTION:

A well-functioning arteriovenous fistula (AVF) is the best modality for vascular access in patients with end-stage renal disease (ESRD) requiring haemodialysis (HD). However, AVFs' main disadvantage is the high rate of maturation failure, with approximately one third (20%-50%) not maturing into useful access. This review examine the use of Far-Infra Red therapy in an attempt to enhance both primary (unassisted) and secondary (assisted) patency rates for AVF in dialysis and pre-dialysis patients.

METHOD:
We performed an online search for observational studies and randomised controlled trials (RCTs) that evaluated FIR in patients with AVF. Eligible studies compared FIR with control treatment and reported at least one outcome measure relating to access survival. Primary patency and secondary patency rates were the main outcomes of interest.

RESULTS:
Four RCTs (666 patients) were included. Unassisted patency assessed in 610 patients, and was significantly better among those who received FIR (228/311) compared to (185/299) controls (pooled risk ratio of 1.23 [1.12-1.35], p=0.00001). In addition, the two studies which reported secondary patency rates showed significant difference in favour of FIR therapy--160/168 patients--compared to 140/163 controls (pooled risk ratio of 1.11 [1.04-1.19], p=0.003).

CONCLUSION:
FIR therapy may positively influence the complex process of AVF maturation improving both primary and secondary patency rates. However blinded RCTs performed by investigators with no commercial ties to FIR therapy technologies are needed.



Far-Infrared Therapy Promotes Nerve Repair following End-to-End Neurorrhaphy in Rat Models of Sciatic Nerve Injury.
Chen TY1, Yang YC2, Sha YN3, Chou JR3, Liu BS3.

Abstract
This study employed a rat model of sciatic nerve injury to investigate the effects of postoperative low-power far-infrared (FIR) radiation therapy on nerve repair following end-to-end neurorrhaphy. The rat models were divided into the following 3 groups: (1) nerve injury without FIR biostimulation (NI/sham group); (2) nerve injury with FIR biostimulation (NI/FIR group); and (3) noninjured controls (normal group). Walking-track analysis results showed that the NI/FIR group exhibited significantly higher sciatic functional indices at 8 weeks after surgery (P < 0.05) compared with the NI/sham group. The decreased expression of CD4 and CD8 in the NI/FIR group indicated that FIR irradiation modulated the inflammatory process during recovery. Compared with the NI/sham group, the NI/FIR group exhibited a significant reduction in muscle atrophy (P < 0.05). Furthermore, histomorphometric assessment indicated that the nerves regenerated more rapidly in the NI/FIR group than in the NI/sham group; furthermore, the NI/FIR group regenerated neural tissue over a larger area, as well as nerve fibers of greater diameter and with thicker myelin sheaths. Functional recovery, inflammatory response, muscular reinnervation, and histomorphometric assessment all indicated that FIR radiation therapy can accelerate nerve repair following end-to-end neurorrhaphy of the sciatic nerve.


 

Far-infrared therapy for cardiovascular, autoimmune, and other chronic health problems: A systematic review.
Shui S1, Wang X2, Chiang JY3, Zheng L4.

Abstract
Physical therapy (physiotherapy), a complementary and alternative medicine therapy, has been widely applied in diagnosing and treating various diseases and defects. Increasing evidence suggests that convenient and non-invasive far-infrared (FIR) rays, a vital type of physiotherapy, improve the health of patients with cardiovascular disease, diabetes mellitus, and chronic kidney disease. Nevertheless, the molecular mechanisms by which FIR functions remain elusive. Hence, the purpose of this study was to review and summarize the results of previous investigations and to elaborate on the molecular mechanisms of FIR therapy in various types of disease. In conclusion, FIR therapy may be closely related to the increased expression of endothelial nitric oxide synthase as well as nitric oxide production and may modulate the profiles of some circulating miRNAs; thus, it may be a beneficial complement to treatments for some chronic diseases that yields no adverse effects.


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