Mouse laser injury models: variations on a theme.

A confluence of technological advances in genetic manipulation and molecular-based fluorescence imaging has led to the widespread adoption of laser injury models to study hemostasis and thrombosis in mice. In all animal models of hemostasis and thrombosis, detailing the nature of experimentally induced vascular injury is paramount in enabling appropriate interpretation of experimental results. A careful appraisal of the literature shows that direct laser-induced injury can result in variable degrees of vascular damage. This review will compare and contrast models of laser injury utilized in the field, with an emphasis on the mechanism and extent of injury, the use of laser injury in different vascular beds and the molecular mechanisms regulating the response to injury. All of these topics will be discussed in the context of how distinct applications of laser injury models may be viewed as representing thrombosis and/or hemostasis.

Noninvasive vascular occlusion with HIFU for venous insufficiency treatment: preclinical feasibility experience in rabbits.

Venous insufficiency is a common disease arising when veins of the lower limb become incompetent. A conventional surgical strategy consists in stripping the incompetent veins. However, this treatment option is invasive and carries complication risks. In the present study, we propose noninvasive high-intensity focused ultrasound (HIFU) to treat lower limbs venous insufficiency, in particular incompetent perforating veins (mean diameter between 2-6 mm). Sonication parameters were designed by numerical simulations using the k-Wave toolbox to ensure continuous coagulation of a vein with a diameter superior or equal to 2 mm. The selected ultrasound exposures were 4 s pulses in continuous wave mode. Two types of sonication were studied: (1) fixed pulses and (2) moving pulses at constant speed (0.75 mm s-1) across the vein. The potential of these exposures to thermally occlude veins were investigated in vivo on rabbit saphenous veins. The impact of vein compression during ultrasonic exposure was also investigated. Fifteen rabbits were used in these trials. A total of 27 saphenous veins (mean diameter 2.0 ± 0.6 mm) were sonicated with a transducer operated at 3 MHz. After a mean 15 d follow-up, rabbits were euthanized and venous samples were extracted and sent for histologic assessment. Only samples with the vein within the HIFU lesion were considered for analysis. Simulated thermal damage distribution demonstrated that fixed pulses and moving pulses respectively placed every 1.5 and 0.5 mm along the vein and delivered at an acoustic power of 85 W and for 4 s were able to induce continuous thermal damages along the vein segments. Experimentally, both treatment parameters (1) and (2) have proven effective to occlude veins with a success rate of 82%. Occlusion was always observed when compression was applied. Our results demonstrate that HIFU can durably and non-invasively occlude veins of diameters comparable to human veins.

A 1470-nm laser combined with foam sclerotherapy in day surgery: a better choice for lower limb varicose veins.

Day surgery is being more and more adopted by clinicians. Higher wavelength lasers give patients better experience than lower wavelength lasers, which makes it more suitable for day surgery. This study compares the short- and mid-term efficacy, postoperative morbidity, and patient satisfaction of "1470-nm endovenous laser ablation (EVLA) combining foam sclerotherapy in day surgery" with "810-nm EVLA with high ligation combining foam sclerotherapy in hospital surgery" on great saphenous vein (GSV) insufficiency postoperatively. A single-institution historical cohort study of 194 patients was performed in Shanghai Ninth People's Hospital, China. Ninety-seven patients received 1470-nm EVLA combining foam sclerotherapy in day surgery ("1470-nm group"), and 97 patients received 810-nm EVLA with high ligation combining foam sclerotherapy in hospital surgery recommended by guidelines ("810-nm group"). No significant difference was found between the 1470-nm group and the 810-nm group in terms of GSV occlusion rate (both 100%), complication rate, and recurrence rate (8.2 vs. 11.3%) during the period of 1-12 months after surgery. Serious complications in the 1470-nm group and 810-nm group were 0 and 1.0%. Minor complications in the 1470-nm group and 810-nm group were ecchymosis at 20.6 and 18.6%, edema at 69.1 and 63.9%, and paresthesia around ankle at 0 and 3.1%, respectively. Advantage of the 1470-nm group over the 810-nm group was statistically significant considering the patient perioperative comfort and economic cost. Treatment of 1470-nm EVLA combining foam sclerotherapy in day surgery has similar efficacy as the 810-nm EVLA with high ligation combining foam sclerotherapy in hospital surgery in GSV insufficiency and is more comfortable with less incision, hospitalization procedure, and medical costs. It may be a new option for patients who are afraid or unable to be hospitalized.

Low-intensity LED therapy (λ 640 ± 20 nm) on saphenectomy healing in patients who underwent coronary artery bypass graft: a randomized, double-blind study.

Myocardial revascularization surgery (CABG) is the most appropriate treatment for coronary artery disease. Currently, the great challenge is to reduce postoperative complications, such as wound infections, dehiscence, pain, and patients' quality of life. The saphenectomy is the target of complications in 10% of cases, which can cause greater morbidity, time, and cost of hospitalization. Studies show that low-intensity laser or light-emitted diode (LED) therapy promotes positive biomodulation of the tissue repair process, culminating in a lower incidence of dehiscence, pain reduction, and improvement in quality of life. The objective of the present study was to evaluate clinically the saphenous tissue repair after LED therapy. Forty subjects of both genders who underwent CABG with extracorporeal circulation were randomly divided into two groups: the placebo (PG) and experimental (EG). The experimental group underwent low-intensity LED therapy (λ 640 ± 20 nm, 6 J/cm2) on saphenectomy. The tissue repair was analyzed by digital photogrammetry on the first and fifth postoperative day. The border closure was blindly evaluated by three researchers. The hematoma and hyperemia area was quantitatively analyzed using ImageJ© software. The results showed that in the experimental group, there were less bleeding points and no dehiscence in saphenectomy, as compared to the placebo group. There was also a smaller area of hematoma and hyperemia in the experimental group (p < 0.0009). These data lead to the conclusion that the type of phototherapy protocol employed can assist in tissue repair.

Effectiveness of Low-Intensity Laser Therapy on Tissue Repair Following Saphenectomy in Patients Who Underwent Coronary Artery Bypass Graft: A Randomized, Double-Blind Study.

OBJECTIVE: To verify the effectiveness of low-intensity laser therapy (LLLT) on tissue repair following saphenectomy during postoperative period in patients having undergone coronary artery bypass graft (CABG). MATERIALS AND METHODS: A randomized clinical trial, controlled and double-blind study was conducted with 40 volunteers, divided into 2 groups: a placebo group (PG, n = 20) and a laser group (LG, n = 20). The patients in the LG group were irradiated with laser during saphenectomy (InGaAlP, λ 660 nm, energy density 6 J/cm2) daily from the first to the fourth postoperative day. The surgical incision was clinically evaluated and imaged at the beginning and at the end of the treatment. The areas of hematoma and hyperemia were evaluated using the software ImageJ 1.4©, and border closure was evaluated by three researchers, who were blinded concerning the allocation of the participants. RESULTS: The LG group presented a reduction of the areas of hematoma and hyperemia (p = 0.0003) and better border closure (p = 0.009), when compared with the PG group. CONCLUSIONS: The proposed LLLT protocol improved the tissue repair following saphenectomy in CABG patients.

Investigation of endovenous laser ablation of varicose veins in vitro using 1.885-µm laser radiation.

This paper presents the results of endovenous laser ablation (EVLA) of varicose veins in vitro using radiation of a solid-state laser based on the crystal LiYF4:Tm, with a wavelength of 1.885 µm and power output of around 3 W. An experimental series with saline solution and red blood cell (RBC) suspension in the venous lumen was performed to identify the impact of a heated carbonized layer precipitated on the fiber end face versus the efficiency of EVLA. Results of these experiments confirmed that the presence of a heated carbonized layer on the fiber end face increases the efficiency of EVLA.

The 1,470-nm bare-fiber diode laser ablation of the great saphenous vein and small saphenous vein at 1-year follow-up using 8-12 W and a mean linear endovenous energy density of 72 J/cm.

PURPOSE: To demonstrate 1-year outcomes after low-energy endovenous laser ablation (EVLA) of incompetent saphenous veins with linear endovenous energy density (LEED) of 80 J/cm or lower with the use of a 1,470-nm diode laser. MATERIALS AND METHODS: Incompetent saphenous veins in 236 patients (355 limbs; Clinical/Etiology/Anatomy/Pathophysiology classifications of C2-C4) were treated by EVLA with a bare-tipped 1,470-nm laser with LEED no greater than 80 J/cm (mean, 72.4 J/cm) and laser power of 8-12 W. Patients were evaluated clinically and with duplex ultrasonography at 1 week and 1, 3, 6, and 12 months after EVLA to assess the technical and clinical success and complication rates. RESULTS: In the 355 limbs, the technical success rate was 100%. The great saphenous vein (GSV) remained occluded in all 229 limbs (100%) after 1 week, 202 of 203 limbs (99.5%) after 1 month, 157 of 158 limbs after 3 months (99.3%), all 99 limbs after 6 months (100%), and all 41 limbs after 1 year (100%). The small saphenous vein (SSV) remained occluded in all 103 limbs (100%) after 1 week, all 94 limbs (100%) after 1 month, 68 of 69 limbs (98.5%) after 3 months, 40 of 41 limbs (97.5%) after 6 months, and all 14 limbs after 1 year (100%). Two GSVs and two SSVs were recanalized and underwent repeated EVLA. No major complications occurred, although bruising (21% of cases), pain (15%), and paresthesia (4%) were observed. CONCLUSIONS: Low-energy EVLA with the use of a 1,470-nm laser with LEED of 80 J/cm or lower is an effective, safe, and technically successful option for the treatment of incompetent saphenous veins.

Photoinduced collagen cross-linking: a new approach to venous insufficiency.

BACKGROUND: What little research has been done on methods of venous valve function recovery with radiofrequency has had disappointing results. Valvuloplasty has some supporters, but the majority of physicians do not consider it a valid therapeutic option. OBJECTIVE: To test a new method of treating varicose veins based on their collagen structure. This procedure it is not a thermal treatment, but it is fast, with significant shrinking and preservation of the endothelium. MATERIALS & METHODS: In the laboratory, we subjected greater saphenous vein specimens to irradiation with a blue light-emitting diode generated (wavelength 450-480 nm) while a riboflavin solution (vitamin B2) was administered. The riboflavin acts as a cross-linking agent, and the blue light as the activator. In this photo-induced reaction, oxygen singlet is produced with oxidative deamination, forming new covalent bonds between collagen fibrils and water. RESULTS: In venous specimens, we demonstrated fast and significant shrinkaged without histologic evidence of endothelial damage and with evident change in mechanical properties of varicose veins. CONCLUSIONS: Photochemically induced collagen cross-linking to restructure varicose veins is only a research field but may become an important tool for recovery of vein diameter and valve function.

Endovenous laser therapy of the small saphenous vein: patient satisfaction and short-term results.

OBJECTIVE: Conventional surgical treatment for small saphenous vein (SSV) reflux is associated with high recurrence rates and complications. Endovenous laser ablation (EVLA) is a treatment modality with promising results. This study reports patient satisfaction and short-term results after EVLA of SSV reflux. METHODS: Fifty-two legs of 49 consecutive patients were treated with EVLA for reflux of the SSV. Patients were investigated clinically and by duplex scanning before and 6 weeks after treatment. Patient records were studied and a questionnaire was completed. RESULTS: Technical success was accomplished in all patients. After 6 weeks the occlusion rate was 100% and after 6.5 months no recurrent varicosities were reported. Complications consisted of bruising (51%), induration (39%), delayed tightness (16%), phlebitis (2%), and temporary paresthesia (6%) and were all self-limiting. One deep venous thrombosis occurred in a patient with a protein C deficiency. Ninety-two percent (45/49) of patients were satisfied with the results and in 98% symptoms had significantly improved or completely disappeared. Working activities were resumed after a mean of 4 days. Forty-three patients (88%) would consider having endovenous laser treatment again if indicated. CONCLUSIONS: EVLA of the SSV seems to be a safe modality with excellent short-term results and high patient satisfaction. Controlled studies assessing the effectiveness of EVLA in comparison to conventional treatment of SSV reflux are crucial before considering EVLA as the standard treatment.

Prophylactic low-energy shock wave therapy improves wound healing after vein harvesting for coronary artery bypass graft surgery: a prospective, randomized trial.

BACKGROUND: Wound healing disorders after vein harvesting for coronary artery bypass graft surgery increase morbidity and lower patient satisfaction. Low-energy shock wave therapy (SWT) reportedly improves healing of diabetic and vascular ulcers by overexpression of vascular endothelial growth fractor and downregulation of necrosis factor kappaB. In this study, we investigate whether prophylactic low-energy SWT improves wound healing after vein harvesting for coronary artery bypass graft surgery. METHODS: One hundred consecutive patients undergoing coronary artery bypass graft surgery were randomly assigned to either prophylactic low-energy SWT (n = 50) or control (n = 50). Low-energy SWT was applied to the site of vein harvesting after wound closure under sterile conditions using a commercially available SWT system (Dermagold; Tissue Regeneration Technologies, Woodstock, GA). A total of 25 impulses (0.1 mJ/mm(2); 5 Hz) were applied per centimeter wound length. Wound healing was evaluated and quantified using the ASEPSIS score. (ASEPSIS stands for Additional treatment, presence of Serous discharge, Erythema, Purulent exudate, Separation of the deep tissue, Isolation of bacteria, and duration of inpatient Stay). Patient demographics, operative data, and postoperative adverse events were monitored. RESULTS: Patient characteristics and operative data including wound length (SWT 39 +/- 13 cm versus control 37 +/- 11 cm, p = 0.342) were comparable between the two groups. We observed lower ASEPSIS scores indicating improved wound healing in the SWT group (4.4 +/- 5.3) compared with the control group (11.6 +/- 8.3, p = 0.0001). Interestingly, we observed a higher incidence of wound healing disorders necessitating antibiotic treatment in the control group (22%) as compared with the SWT group (4%, p = 0.015). No SWT-associated adverse events were observed in the treatment group. CONCLUSIONS: As shown in this prospective randomized study, prophylactic application of low-energy SWT improves wound healing after vein harvesting for coronary artery bypass graft surgery.

[Application of irradiated allograft vascular in the liver transplantation].

OBJECTIVE: To study the substitute portal vein by irradiated allograft saphenous vein during liver transplantation and investigate the changes in morphology and immunology. METHODS: All the recipients were divided into 3 groups randomly:irradiated allograft group (n = 11) (group A), fresh allograft group (n = 9) (group B) and fresh self-graft group (n = 14) (group C). The number of non-jam graft vessels in each group was explored at 1st week, 2nd week, 1st month, 2nd month and 3rd month post-operation. Also, the infiltration of CD(4)(+), CD(8)(+) T cells and histological changes in grafted vessels were detected. RESULTS: No obvious histological changes were observed in group A, as well as under naked eyes. There were 9, 3 and 12 non-jam vessels in group A, B and C and there were significant differences between group A and B (P < 0.05). The endothelial cells of graft vessels were observed both in group A and C two weeks post-operation and covered the graft vessels two months later. There were infiltration of lymphocytes and inflammatory cells at early stage, obvious damage and no endothelial cells growth in graft vessels in group B. Compared with group B, the percentage of CD(4)(+), CD(8)(+) T cells in group A was lower significantly, but higher slightly than that in group C. CONCLUSIONS: Irradiated allograft saphenous veins have the quality of ideal vascular transplantation prosthesis and weak antigenicity at the same time. The changes of CD(4)(+), CD(8)(+) T cells after allograft vessels can be detected as immunology index for acute immunological rejection.

The first 1000 cases of Italian Endovenous-laser Working Group (IEWG). Rationale, and long-term outcomes for the 1999-2003 period.

AIM: The innovations for disease management need to be thoroughly evaluated so that their benefits and potential downsides can be compared with the already existing approaches. Endovascular laser (EVL) treatment for varicose veins offers today several advantages over surgical standard stripping. The Italian Endovenous-laser Working Group (IEWG) is a homogeneous group of surgeons and phlebologists who have been using EVL since 1999 and has undertaken to examine EVL in a multicenter study starting from a well defined rationale, with the benefit of a single protocol to use. METHODS: In a cooperative, multicenter, clinical study, 1076 limbs in 1050 patients, mean age of 54.5 years, 241 males and 809 females affected by chronic venous insufficiency (CVI) were considered eligible for surgery and stratified by CEAP classification in a four-year period (January 1999 December 2003). Inclusion criteria were insufficiency of the great and/or small saphenous vein at various levels, beyond those accessory saphenous trunks with incompetence in the saphenofemoral junction. In all cases truncular reflux apparead up on duplex scan examination, with or without associated varicosities. All the patients underwent a surgery on the basis of the clinical assessment. All the centres involved performed treatment in conformity with the Food and Drug Administration (FDA) validated procedure, using an endo-laser venous system kit with a 810-980 nm diode. Duplex scan was performed in all patients after 36 months with very few lost to follow-up cases. RESULTS: In the immediate postoperative period the results have been impressive, with a very effective closure of incompetent great saphenous vein and the other treated varicose veins (the early occlusion rate has been 99%). Major complications have not been detected: in particular, no deep venous thrombosis (DVT) evaluated duplex ultrasound. The patients' acceptability and satisfaction regarding the procedure, have been measured by means of a questionnaire on the quality of life, and the result was 96.7%. After 36 months, the total occusion rate of saphenous trunks has been 97%. CONCLUSIONS: The first important Italian experience with EVL based on preoperative, perioperative and postoperative duplex control and which is also based on the patients' satisfaction at mid/long-term has indicated some advantages over the standard treatment with the stripping method. In terms of reduced postoperative pain, shorter sick leave, a faster resumption of the normal activities, and, in particular, the total absence of DVT, we can conclude that EVL is a good solution for all patients with anatomic and hemodinamic patterns for saphenous vein surgery.

Mathematical modeling of endovenous laser treatment (ELT).

BACKGROUND AND OBJECTIVES: Endovenous laser treatment (ELT) has been recently proposed as an alternative in the treatment of reflux of the Great Saphenous Vein (GSV) and Small Saphenous Vein (SSV). Successful ELT depends on the selection of optimal parameters required to achieve an optimal vein damage while avoiding side effects. Mathematical modeling of ELT could provide a better understanding of the ELT process and could determine the optimal dosage as a function of vein diameter. STUDY DESIGN/MATERIALS AND METHODS: The model is based on calculations describing the light distribution using the diffusion approximation of the transport theory, the temperature rise using the bioheat equation and the laser-induced injury using the Arrhenius damage model. The geometry to simulate ELT was based on a 2D model consisting of a cylindrically symmetric blood vessel including a vessel wall and surrounded by an infinite homogenous tissue. The mathematical model was implemented using the Macsyma-Pdease2D software (Macsyma Inc., Arlington, MA, USA). Damage to the vein wall for CW and single shot energy was calculated for 3 and 5 mm vein diameters. In pulsed mode, the pullback distance (3, 5 and 7 mm) was considered. For CW mode simulation, the pullback speed (1, 2, 3 mm/s) was the variable. The total dose was expressed as joules per centimeter in order to perform comparison to results already reported in clinical studies. RESULTS: In pulsed mode, for a 3 mm vein diameter, irrespective of the pullback distance (2, 5 or 7 mm), a minimum fluence of 15 J/cm is required to obtain a permanent damage of the intima. For a 5 mm vein diameter, 50 J/cm (15W-2s) is required. In continuous mode, for a 3 mm and 5 mm vein diameter, respectively 65 J/cm and 100 J/cm are required to obtain a permanent damage of the vessel wall. Finally, the use of different wavelengths (810 nm or 980 nm) played only a minor influence on these results. DISCUSSION AND CONCLUSION: The parameters determined by mathematical modeling are in agreement with those used in clinical practice. They confirm that thermal damage of the inner vein wall (tunica intima) is required to achieve the tissue alterations necessary in order to lead the vein to permanent occlusion. However, in order to obtain a high rate of success without adverse events, the knowledge of the vein diameter after tumescent anesthesia is recommended in order to use the optimal energy. As clearly demonstrated by our calculations, both pulsed and continuous mode operations of the laser can be efficient. An interesting observation in our model is that less amount of energy is required in pulsed mode than in continuous mode. Damaging the vein sequentially along its entire length may lead to permanent occlusion. However, the pulsed mode requires a very precise positioning of the fiber after each pullback and the duration of the treatment is much longer. For these reasons, continuous irradiation seems to be preferred by most clinicians. This model should serve as a useful tool to simulate and better understand the mechanism of action of the ELT.

Botulinum toxin potentiates cancer radiotherapy and chemotherapy.

PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.

Endovenous treatment of the great saphenous vein using a 1,320 nm Nd:YAG laser causes fewer side effects than using a 940 nm diode laser.

BACKGROUND: Limited data are available about treatment-related side effects with respect to laser wavelength in endovenous laser treatment (ELT) of the great saphenous vein (GSV). OBJECTIVE: To compare the results and side effects of a 940 nm diode and a 1,320 nm neodymium:yttium-aluminum-garnet (Nd:YAG) laser. METHODS: Three patient cohorts (A, B, and C) received ELT of the GSV using a 940 nm diode laser at 15 W (group A) or 30 W (group B) or using a 1,320 nm laser at 8 W (group C). In all cases, energy was administered continuously with constant pullback of the laser fiber under perivenous tumescent local anesthesia. RESULTS: The GSVs of group A (n = 113), group B (n = 136), and group C (n = 33) received ELT. An average linear endovenous energy density of 24, 63, and 62 J/cm and an average endovenous fluence equivalent of 12, 30, and 33 J/cm2 were administered to the vein. Occlusion rates were 95% (group A), 100% (group B), and 100% (group C) at day 1 after ELT and 90.3% (group A), 100% (group B), and 97% (group C) at 3 months after ELT. With the 1,320 nm laser ELT (group C), treatment-related pain (50%) and the need for analgesics (36%) were significantly reduced (p < .005) in comparison with treatment-related pain (81%) and the need for analgesics (67%) after the 30 W 940 nm laser ELT (group B). Ecchymosis was also significantly reduced (p < .05) in group C (1,320 nm) compared with group B (30 W, 940 nm). CONCLUSION: ELT of the GSV using a 1,320 nm Nd:YAG laser causes fewer side effects compared with 940 nm diode laser ELT.

Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for patients with diffuse in-stent restenosis.

BACKGROUND: The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy. We sought to examine whether an escalation in dose to 21 Gy is safe and confers additional benefit in reducing repeat revascularization and major adverse cardiac events (MACE) in patients with diffuse ISR. METHODS: Forty-seven patients with diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and saphenous vein grafts (n=22) underwent percutaneous transluminal coronary angioplasty and/or additional stents followed by IRT-gamma using the Checkmate system (Cordis) with a dose of 21 Gy. All patients were discharged with clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12-month clinical outcomes of these patients were compared to 120 patients treated with 18 Gy using the same system. RESULTS: At baseline, patients in the 21-Gy group had more multivessel, vein graft disease and history of prior myocardial infarctions and coronary artery bypass grafts (P<.001). The use of debulking devices and stents was less in this group (P<.001). Procedural and in-hospital complications were similar. Follow-up at 6 months revealed nonsignificant but lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward less overall myocardial infarction, although repeat revascularization and MACE rates were similar. CONCLUSIONS: IRT-gamma therapy for diffuse ISR lesions with a 21-Gy dose is clinically safe and feasible with marked reduction in late loss but does not confer additional benefit with regard to repeat revascularization and MACE when compared to a dose of 18 Gy.

Treatment of in-stent restenosis for saphenous vein grafts using intravascular brachytherapy: regulatory challenges and clinical application.

Treatment of in-stent restenosis using intravascular brachytherapy (IVBT) has been demonstrated to be successful and has become the standard of care for native coronary artery disease. Based on the current Food and Drug Administration (FDA) indications for use and the clinical demand to increase the scope of this form of therapy to include saphenous vein grafts for the Beta-Cath System (Novoste Corporation, Norcross, Georgia), we set out to obtain institutional approval for off-label use. Identification of institutional regulatory bodies and related procedures for obtaining off-label device use was performed. Additionally, the IVBT written directive proscription and patient informed consent forms were revised to accurately administer radiation dose and to disclose the regulatory status of using IVBT for this anatomic site. While the specifics are outlined in this report, this process and the resources needed to obtain institutional approval for off-label use are indicative of that to be expected at similar institutions.

Beta brachytherapy of an old degenerated saphenous vein graft with occlusive in-stent restenosis.

We report a case of obstructive in-stent restenosis in a diffusely diseased saphenous vein graft complicated by a non-ST-elevation myocardial infarction. With tirofiban infusion, the extensively occluded saphenous bypass was reperfused, establishing a TIMI flow 3, and then entirely irradiated with a beta source (32P) without any complication. At 7 months the patient was asymptomatic and the control angiogram did not reveal any restenosis. In conclusion, 32P beta brachytherapy may be extremely effective not only in case of native vessel in-stent restenosis but also in cases of high-risk vein graft in-stent restenosis.

The effect of radiation on the permeability of human saphenous vein to 17 beta-oestradiol.

Radiation therapy is an effective way of treating many forms of cancer, however, there are some indications that it may facilitate the development of metastasis. The question arises whether radiation therapy during cancer treatment might result in an alteration of the permeability of the tissues being treated. This alteration in the permeability might lead to metastatic cells escaping from the irradiated tissue, leading to the spread of cancer to other sites in the body. Because of the above implication, we determined the diffusion kinetics of a radioactive marker, 17 beta-oestradiol, through human saphenous vein before and after a single half hour exposure to 60 Gy of 60Co gamma-irradiation. Six clinically healthy saphenous vein specimens (mean patient age +/- standard deviation 57 +/- 13 years; age range 41-77 years) were obtained during cardiac surgery. In vitro flux rates of 17 beta-oestradiol were determined through use of a flow-through diffusion apparatus immediately after irradiation for a period of 24 hours. No statistically significant differences could be demonstrated for the flux rates of 17 beta-oestradiol through the non-irradiated and 60 Gy irradiated saphenous vein tissue. These findings strongly suggest that irradiation at 2 Gy/min and a total dose of 60 Gy would not alter the permeability of the venous wall. We have demonstrated that the in vitro flow-through diffusion method is capable of measuring permeability aspects of endothelial cell layers in saphenous vein biopsies under conditions resembling clinical reality.