C3d deposition in the media of renal arterioles is a useful marker for arteriolosclerosis in IgA nephropathy.

C3d deposition in peritubular capillaries has been demonstrated to indicate antibody-mediated alloresponse during renal transplantation. C3d deposition in renal arterioles in IgA nephropathy (IgAN), however, is poorly documented. Especially, its significance to the pathology of primary glomerulonephritis remains unclear. This retrospective study included 340 patients with IgAN who underwent renal biopsy at our center. C3d strongly positive deposition in arterioles was observed in 123 (36.2%) of the 340 cases, and weakly positive deposition of C3d was observed in 217 cases (63.8%). In the weakly positive group, C3d mainly deposited in the intima of arterioles. In the strongly positive group, C3d deposited in the intima and the media of arterioles, presenting as the medial thickening and sclerosis of varying severities. The prognosis was worse in the C3d strongly positive group than in the weakly positive group during a 2-year follow-up (P = .027). The predictive value of C3d deposition in the media of arterioles in patients with IgAN may be a useful marker for arteriolosclerosis indicating unfavorable clinical outcomes.

Effects of external irradiation of the neck region on intima media thickness of the common carotid artery.

BACKGROUND: Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels. OBJECTIVES: To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race. METHODS: We studied 19 patients (10 male; 47.8 +/- 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 +/- 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 +/- 17.6) were recruited as a control group. RESULTS: IMT was not significantly higher in patients when compared to the control group (0.59 +/- 0.16 vs 0.56 +/- 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age < or = 52 years) had IMT measurements higher (0.54 +/- 0.08 mm) than the non-irradiated young patients (0.49 +/- 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04). CONCLUSION: This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries.

Combining sirolimus-eluting stents and external irradiation in cholesterol-fed rabbits increased incomplete stent apposition and decreased re-endothelialization.

Restenosis after the implantation of a drug-eluting stent or after vascular irradiation therapy shares similar physiopathological mechanisms. No experimental data are currently available on vascular wall behavior after external irradiation on arteries stented with sirolimus-eluting stents (SES). Ten New Zealand white rabbits received a 0.5% cholesterol-enriched chow for 1 month. Bilateral iliac artery stent implantation was then performed with an SES (Cypher; Cordis Corp). The animals were randomized into either an irradiated group (I, 2 Gy external x-ray irradiation, n = 5) or a control group (C, n = 5). The cholesterol-enriched chow was continued for 1 additional month after stent implantation. The stented arteries were harvested for histological analyses. The number and the percentage of incompletely apposed stents struts (IASS) were significantly higher in irradiated versus control group (3.05 +/- 0.46 vs. 1.57 +/- 0.27 IASS, P < 0.01, and 28.44% +/- 3.97% vs. 15.2% +/- 2.46% of IASS, P < 0.01, respectively). The mean neointimal thickness behind the IASS was also higher in the irradiated group (I: 28.3 +/- 2.5 microm vs. C: 18.2 +/- 2.3 microm, P < 0.01). Re-endothelialization was lower in irradiated group (I: 44.6% +/- 17.5% vs. C: 75.2% +/- 5.7%, P < 0.01). The present study revealed that low-dose external irradiation increased incomplete stent apposition and reduced re-endothelialization of SES. These results underscore the potential deleterious cumulative side effects of these 2 procedures to prevent restenosis.

Transplantation of Bone Marrow Mesenchymal Stem Cells Prevents Radiation-Induced Artery Injury by Suppressing Oxidative Stress and Inflammation.

The present study aims to explore the protective effect of human bone marrow mesenchymal stem cells (hBMSCs) on radiation-induced aortic injury (RIAI). hBMSCs were isolated and cultured from human bone marrow. Male C57/BL mice were irradiated with a dose of 18-Gy 6MV X-ray and randomly treated with either vehicle or hBMSCs through tail vein injection with a dose of 103 or 104 cells/g of body weight (low or high dose of hBMSCs) within 24 h. Aortic inflammation, oxidative stress, and vascular remodeling were assessed by immunohistochemical staining at 3, 7, 14, 28, and 84 days after irradiation. The results revealed irradiation caused aortic cell apoptosis and fibrotic remodeling indicated by aortic thickening, collagen accumulation, and increased expression of profibrotic cytokines (CTGF and TGF-ß). Further investigation showed that irradiation resulted in elevated expression of inflammation-related molecules (TNF-α and ICAM-1) and oxidative stress indicators (4-HNE and 3-NT). Both of the low and high doses of hBMSCs alleviated the above irradiation-induced pathological changes and elevated the antioxidant enzyme expression of HO-1 and catalase in the aorta. The high dose even showed a better protective effect. In conclusion, hBMSCs provide significant protection against RIAI possibly through inhibition of aortic oxidative stress and inflammation. Therefore, hBMSCs can be used as a potential therapy to treat RIAI.

Mechanisms of late lumen loss after antiproliferative percutaneous coronary intervention using beta-irradiation in a porcine model of restenosis.

BACKGROUND: The short-term results for the prevention of coronary restenosis after intravascular brachytherapy (IVBT) and use of drug-eluting stents (DESs) are excellent. The long-term results either lack or present with late complications (e.g., late thrombosis and late catch-up phenomenon leading to late restenosis even years after the initial procedure). Both IVBT and DESs mediate their potent antirestenotic effects via a cytostatic mechanism, but the cardiovascular pathology at late time points after the use of these antiproliferative therapies is incompletely understood. This study investigated the long-term effects of antiproliferative beta-irradiation in a clinically relevant porcine coronary model to address the pathophysiology of late coronary restenosis after antiproliferative vascular interventions. METHODS: We performed percutaneous transluminal coronary angioplasty (PTCA) in two major coronary arteries in 12 domestic crossbred pigs. One of the two balloon-injured segments was randomly assigned to receive immediate beta-irradiation (PTCA+IVBT group) using a noncentered delivery catheter (20 Gy; Novoste Beta-Cath System, Novoste, Norcross, GA, USA). The animals were sacrificed after 14 days (n=6) or 3 months (n=6). RESULTS: The luminal area in the PTCA+IVBT group decreased significantly 3 months after the intervention as compared with that in the PTCA group (PTCA 3.45+/-0.46 mm2 vs. PTCA+IVBT 1.22+/-0.26 mm2; P=.0017). This lumen loss was primarily due to shrinkage of the external elastic lamina area (negative arterial remodeling; PTCA 5.22+/-0.27 mm2 vs. PTCA+IVBT 3.42+/-0.45 mm2; P=.0064), which was accompanied by an increase in the adventitial area (PTCA 3.07+/-0.2 mm2 vs. PTCA+IVBT 5.41+/-0.5 mm2; P=.0049). CONCLUSIONS: The application of antiproliferative radiation in a porcine coronary model caused an early beneficial effect (reduction of intimal-medial lesion and luminal gain) that was followed by a late lumen loss primarily due to negative arterial remodeling. This mechanism may in part help us understand the pathophysiology of late adverse events occurring after IVBT.

Is radiation a risk factor for atherosclerosis? An echo-color Doppler study on Hodgkin and non-Hodgkin patients.

AIMS AND BACKGROUND: The aim of the present paper was to study the role of irradiation in the atherosclerotic process in patients affected by Hodgkin and non-Hodgkin lymphoma. METHODS: We studied 84 subjects, 42 with Hodgkin or non-Hodgkin disease and 42 controls. All 42 cases had been irradiated and were comparable in terms of risk factors for atherosclerosis. All 84 subjects underwent echo-color Doppler of the arterial axis (carotids, abdominal aorta, and femoral arteries), and the intima-media thickness was measured. RESULTS: The irradiated cases had a greater intima-media thickness in the carotid district, even after dividing them according to age and sex; males were affected more than females. The irradiated patients were at greater risk of developing cardiovascular events than the controls. CONCLUSIONS: An echo-color Doppler of the carotid district is advisable in all patients who have been submitted to radiotherapy, and the patients with a significantly greater than normal intima-media thickness need a strict follow-up, and antioxidant or antiaggregant therapy should be considered.

Prophylaxis of restenosis with (186)re-labeled stents in a rabbit model.

BACKGROUND: Intraluminal beta-irradiation has been shown to decrease neointimal proliferation after angioplasty in experimental models. The purpose of this study was to test the technical feasibility and biological effects of (186)Re-labeled stents. METHODS AND RESULTS: Thirty-four New Zealand White rabbits were fed a 0.5% cholesterol diet before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were killed 7 weeks after stent implantation. Two of 34 animals died prematurely (aortic leak, pneumonia). Control stents (n=7) were compared with (186)Re stents (2.6 MBq [n=6], 8.1 MBq [n=5], 16.0 MBq [n=6], and 25.3 MBq [n=8]). Stent application was successful in all cases. No thrombus occlusion was observed. After 7 weeks, neointima formation was 2.2+/-0.2 mm(2) in the control group. In the treatment groups, a dose-dependent neointima reduction was detectable (0.5+/-0.5 mm(2) [2.6 MBq], 0.4+/-0.4 mm(2) [8.1 MBq], and 0 mm(2) [16.0 MBq, 25.3 MBq]). No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed reendothelialization. CONCLUSIONS: (186)Re stents were capable of reducing neointima formation in a dose-dependent fashion. (186)Re stents did not cause late thrombosis or neointimal induction at the stent margins in the observation period of 7 weeks.

Canine carotid allograft changes after photochemotherapy and external polyester sheathing.

BACKGROUND: The purpose of this study is to define and refine the changes in canine carotid allografts after photochemotherapy and polyester sheathing. Photochemotherapy with 8-methoxy psoralen (8MOP) and UVA (PUVA) was given alone or combined with intraluminal visible light (VL) 450 nm in proper dosages to speed the depopulation of endothelial (EC) and smooth muscle cells (SMC) and to modulate the immune response. METHODS: Novel apparati were made for photochemotherapy of 19 right canine carotid arterial allografts with 19 paired untreated controls in the left carotid. External UVA and internal visible light (VL 450 nm) were used with 8-methoxy psoralen (8-MOP) as a sensitizer. RESULTS: With moderate dosage of 8-MOP (1 microg/cc) and 2-4 J/cm2 of external UVA (PUVA), smooth muscle cells (SMC) disappeared faster from the media and fibroblasts (FB) appeared earlier in the adventitia of the treated right allografts, reducing but not eliminating the immune response. Intraluminal VL did not enhance the PUVA effect. At 68 days, treated and control allografts showed similar dimensions with subsided immune reactions. The media thickness was reduced from 0.38 mm to 0.18 mm and the host adventitia increased from 0.22 to 0.60 mm. Variable reactions peaked between two and three weeks and subsided after one month. All allografts remained open with canine carotid i.d.s of 2-3 mm and 80 to 100 cc/ minute arterial flows. Although the UVA dosage was moderate) similar doses sterilized log 7 of staph aureus cultures in saline. The allografts without smooth muscle showed moderate but stable cylindrical dilatation without spasm or stenosis and with an adequate adventitial buttress for a small vessel. A polyester sleeve around four treated grafts was inseparable from the allograft in less than 3 weeks and tolerated well over a 70-day period. CONCLUSIONS: Biodegradable graft sheaths with bioerodible hydrogels with growth factors (FGF) for local delivery may provide a faster and more complete matrix remodeling for a superior conduit in the future.

[High-dose external ionizing radiation prevents intimal hyperplasia and limits secretion of growth factors PDGFbb, bFGF, and TGFb1. Experiments and results]. / Les radiations ionisantes externes à doses élevées limitent l'hyperplasie intimale et diminuent la sécrétion des facteurs de croissance PDGF-bb, bFGF et TGFb1. Expérimentation et résultats.

PURPOSE: To evaluate the ionizing radiation for intimal hyperplasia prevention and to assess the production of growth factors. METHODS: An oversized injury using an embolectomy catheter was performed on a rabbit distal aorta (N=23), associated (test group; N=12) or not (control group; N=11) with a post-operative external radiation (25 Gy). At t=45 days, histological studies and morphometric studies were performed on the aorta. Smooth muscular cells and endothelial cells were stained using immuno-histologic revelation. Immuno-histological analysis was performed on arteries for growth factors PDGFbb, bFGF and TGFb1. RESULTS: Twenty-one animals survived the procedure, 11 were in the test group and 10 in the control group. Intimal thickness and ratio intima/media were significantly lower after radiation (respectively p=0.008, p=0.008). There was no difference for the medial thickness (p=0.155). Immuno-histochemical positive staining for PDGF and TGFb1 was lower after radiation (respectively 18.44 +/- 2.963% versus 47.64 +/- 6.86%, p<0.001 and 10.11 +/- 3.18% versus 29.45 +/- 4.156%, p<0.001). There was no difference for the expression of bFGF growth factor. After radiation, the media was found to be reduced and replaced by interstitial fibrosis. CONCLUSION: After external radiation the thickness parameter of the intima and the ratio intima/media decreased significantly in comparison with the control group. PDGF and TGFb1 were also less expressed in the artery irradiated. Fibrosis recasting needs to be confirmed by further investigation.

Intimal-medial thickness and carotid arteries lumen in irradiated patients for head and neck cancer: preliminary data of an observational study.

OBJECTIVES: To investigate the effect of external beam radiotherapy (EBRT) for head and neck cancer (HNC) the intimal-medial thickness (IMT) and the lumen of the carotid artery. METHODS: Patients with HNC and an indication for EBRT were enrolled. A carotid artery color Doppler examination was performed before and 6 and 12 months after EBRT. RESULTS: From 2008 to 2011, 50 patients were enrolled. The mean carotid IMT was 0.9 vs. 1.02 mm before and 6 months after EBRT, respectively (p = 0.0001). The common carotid artery lumen was narrowed without statistical significance, 6 months after EBRT (p = 0.3). 1 year from EBRT, the IMT increase and the lumen reduction were statistically significant (p = 0.001, p = 0.01, respectively). Neurological events (stroke or TIA) were not observed. CONCLUSIONS: Our data showed a significant IMT increase 6 months from EBRT without a corresponding narrowing of the common carotid lumen while a significant increase 12 months after EBRT.

Effect of neoadjuvant chemoradiation and postoperative radiotherapy on expression of heat shock protein 70 (HSP70) in head and neck vessels.

BACKGROUND: Preoperative radiotherapy and chemotherapy in patients with head and neck cancer result in changes to the vessels that are used to construct microsurgical anastomoses. The aim of the study was to investigate quantitative changes and HSP70 expression of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses. METHODS: Of 20 patients included in this study five patients received neoadjuvant chemoradiation, another five received conventional radiotherapy and 10 patients where treated without previous radiotherapy. During surgical procedure, vessel specimens where obtained by the surgeon. Immunhistochemical staining of HSP70 was performed and quantitative measurement and evaluation of HSP70 was carried out. RESULTS: Conventional radiation and neoadjuvant chemoradiation revealed in a thickening of the intima layer of recipient vessels. A increased expression of HSP70 could be detected in the media layer of the recipient veins as well as in the transplant veins of patients treated with neoadjuvant chemoradiation. Radiation and chemoradiation decreased the HSP70 expression of the intima layer in recipient arteries. Conventional radiation led to a decrease of HSP70 expression in the media layer of recipient arteries. CONCLUSION: Our results showed that anticancer drugs can lead to a thickening of the intima layer of transplant and recipient veins and also increase the HSP70 expression in the media layer of the recipient vessels. In contrast, conventional radiation decreased the HSP70 expression in the intima layer of arteries and the media layer of recipient arteries and veins. Comparing these results with wall thickness, it was concluded, that high levels of HSP70 may prevent the intima layer of arteries and the media layer of vein from thickening.

Tolerance of arteries to microplanar X-ray beams.

PURPOSE: The purpose is to evaluate effects of a new radiotherapy protocol, microbeam radiation therapy, on the artery wall. In previous studies on animal models, it was shown that capillaries recover well from hectogray doses of X-rays delivered in arrays of narrow (< or = 50 microm) beams with a minimum spacing of 200 microm. Here, short- and long-term effects of comparable microplanar beam configurations on the saphenous artery of the mouse hind leg were analyzed in situ by use of nonlinear optics and compared with histopathologic findings. METHODS AND MATERIALS: The left hind leg of normal mice including the saphenous artery was irradiated by an array of 26 microbeams of synchrotron X-rays (50 microm wide, spaced 400 microm on center) with peak entrance doses of 312 Gy and 2,000 Gy. RESULTS: The artery remained patent, but narrow arterial smooth muscle cell layer segments that were in the microplanar beam paths became atrophic and fibrotic in a dose-dependent pattern. The wide tunica media segments between those paths hypertrophied, as observed in situ by two-photon microscopy and histopathologically. CONCLUSIONS: Clinical risks of long-delayed disruption or occlusion of nontargeted arteries from microbeam radiation therapy will prove less than corresponding risks from broad-beam radiosurgery, especially if peak doses are kept below 3 hectograys.

Vascular radiolesion as a deleterious effect of high-dose-rate intraarterial brachytherapy with samarium-153 in hypercholesterolemic rabbits.

OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11% and 15-Gy IG: 14.29%, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33% and 15-Gy IG:0%, p=0.0001) and vascular proliferation (60-Gy IG:30.56% and 15-Gy IG:0%, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.

External beam irradiation in angioplasted arteries of hypercholesterolemic rabbits. The dose and time effect.

PURPOSE: To study the dose and time effect of external beam irradiation on the morphometry of both angioplasted and nonangioplasted arteries in a hypercholesterolemic rabbit model. METHODS AND MATERIALS: Eight groups of rabbit femoral arteries were studied: arteries (a) with no intervention, (b) irradiated with a 12-Gy 6 MV X-ray dose, (c) with a 18-Gy, (d) treated with balloon angioplasty, (e) dosed with 12-Gy half an hour post-angioplasty, (f) dosed with 18-Gy half an hour post-angioplasty, (g) dosed with 12-Gy 48 h post angioplasty, (g) dosed with 18-Gy 48 h post angioplasty. RESULTS: External irradiation at either 12 or 18 Gy was not found to change vessel morphometry in noninjured arteries. The 12-Gy dose given soon after angioplasty further increased percentage stenosis (63% on the average), despite the preservation of the lumen cross-sectional area. Positive remodeling was not observed in arteries given 18-Gy half an hour post angioplasty to counterbalance the increased neointimal formation. Therefore, this treatment resulted in a drastic reduction in lumen area and in enhancement of percentage stenosis (84% on the average). On the contrary, the delayed irradiation of the angioplasted arteries at either 12 or 18 Gy was not found to influence any of the studied morphometric parameters 5 weeks after angioplasty. CONCLUSIONS: Uniform external beam irradiation up to 18 Gy was well tolerated by intact femoral arteries. Prompt 12- or 18-Gy irradiations accentuated percentage stenosis. However the lumen cross-sectional area was preserved only at the lower dose point. Delayed irradiation at any dose did not influence the restenosis process.

Carotid intima-media thickness in patients with head and neck irradiation for the treatment of nasopharyngeal carcinoma.

AIM: Intima-media thickness (IMT) has been shown to be useful in the evaluation and monitoring of carotid artery atherosclerosis in patients at risk of cardiovascular events. In this study, we aimed to examine the IMT in patients with nasopharyngeal carcinoma (NPC) who received irradiation to the carotid arteries during radiotherapy, and compared them with a control group. MATERIALS AND METHODS: Fifty-one NPC patients (aged between 39 and 69 years) and a group of 51 age-and sex-matched controls were studied by ultrasound. The IMT at the far wall of the common carotid artery was measured three times and the average value taken in each subject. The IMT of both groups were compared. Risk factors for IMT thickness, including hypertension, smoking, hyperglycaemia, hypercholesterolaemia, history of cerebrovascular accidents and cardiovascular disease, were also studied. RESULTS: The mean carotid IMT of patients in the NPC group (2.2+/-1.5 mm) was statistically greater than that in normal controls (0.7+/-0.15 mm) (P < 0.05). There was no statistically significant difference between the IMT in the right and left common carotid arteries within each group of patients. CONCLUSION: The findings suggest that patients with irradiation have increased arterial IMT. As they are asymptomatic the clinical relevance is not clear.

Effect of intravascular irradiation on cell proliferation, apoptosis, and vascular remodeling after balloon overstretch injury of porcine coronary arteries.

BACKGROUND: Ionizing radiation has been shown to reduce vascular lesion formation after balloon overstretch injury of pig coronary arteries. The present series of experiments examines the mechanism by which this occurs. METHODS AND RESULTS: Balloon injury was performed on porcine coronary arteries, followed immediately by ionizing radiation using either a source train of 90Sr/Y or 192Ir seeds designed to deliver 14 or 28 Gy at a depth of 2 mm from the source. The animals were killed 3, 7, or 14 days after injury. Bromodeoxyuridine was administered 24 hours before euthanasia to label proliferating cells. Cell proliferation was significantly reduced on day 3 in the adventitia and media of the irradiated vessels compared with controls. Two weeks after injury, there were fewer alpha-actin-positive myofibroblasts in the adventitia of the irradiated vessels than in nonirradiated controls, and morphometric analysis indicated that the vessel perimeter of the irradiated vessels was significantly larger than in controls. Together, these results suggest a positive effect of intravascular irradiation on vascular remodeling. Apoptosis was estimated by terminal transferase dUTP-biotin nick-end labeling (TUNEL) 3 and 7 days after injury. TUNEL-labeled cells were found primarily in the adventitia at the medial tear, but no differences were detected between irradiated and control vessels. CONCLUSIONS: These studies suggest that intracoronary radiation primarily inhibits the first wave of cell proliferation in the vessel wall and demonstrates a favorable effect on late remodeling by preventing adventitial fibrosis at the injury site.

Characterization of pulsed-dye laser-mediated vasodilatation in a rabbit femoral artery model of vasoconstriction.

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.

Asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma.

PURPOSE: To determine the prevalence and severity of asymptomatic carotid arterial disease in young patients following neck radiation therapy for Hodgkin lymphoma and to compare the prevalence of carotid arterial disease following radiation therapy alone with that following radiation therapy and chemotherapy. MATERIALS AND METHODS: Forty-two survivors of childhood or early adult Hodgkin lymphoma aged 18-37 years who had undergone radiation therapy more than 5 years earlier underwent carotid arterial ultrasonography. Common carotid intima-media thickness was measured; carotid vessels were assessed for intima-media abnormalities. Results were compared with those from 33 control subjects. RESULTS: Patients had a significantly greater number of abnormal scans than did control subjects (11 [26%] vs one [3%]; P < .01). Ten patients (24%) had intima-media abnormalities that did not cause significant stenosis; one patient had diffuse bilateral intima-media thickening (mean, 1.99 mm) with greater than 70% stenosis of both common carotid arteries. Intima-media thickness was significantly greater in patients (0.51 mm) than in control subjects (0.43 mm; P < .005). The number of abnormalities in patients with radiation therapy plus chemotherapy (six [19%] of 31 patients) did not differ significantly from the number in patients with only radiation therapy (five [45%] of 11 patients; P = .12); there was no significant difference between median intima-media thicknesses (0.50 mm vs 0.51 mm, P > .2). CONCLUSION: Asymptomatic carotid arterial disease occurs frequently in young patients following neck radiation therapy for Hodgkin lymphoma. No difference in prevalence was shown between only radiation therapy and radiation therapy plus chemotherapy.

Mechanisms of coronary hyperconstriction in response to serotonin induced by X-irradiation in miniature pigs: increased constrictive response of medial smooth muscle.

Experimental and clinical studies suggest that X-irradiation to the coronary artery may enhance vasoconstrictive response. This study aimed to clarify the effect of X-irradiation on the vasomotor response of porcine coronary artery. X-ray (15 Gy) was selectively irradiated to the left anterior descending coronary artery (LAD) in 14 Göttingen miniature pigs. The coronary vasomotor responses to serotonin at the irradiated site (LAD) and the control site (the left circumflex artery; LCX) were assessed by quantitative arteriography before and 1 h and 1, 2, and 4 weeks after X-irradiation. At 2 weeks, endothelium-dependent vasodilation in response to substance P was also evaluated arteriographically in vivo. At 2 weeks, isometric tension studies were performed to evaluate the constrictive responses of medial muscle strips and endothelium-dependent relaxation. Coronary vasoconstriction in response to serotonin was enhanced 1 week after, and further augmentation was noted 2 and 4 weeks after X-irradiation. Endothelium-dependent vasodilation in response to substance P in vivo was preserved 2 weeks after X-irradiation. Coronary arteriography showed no organic stenosis at the irradiated site. In vitro studies demonstrated that medial muscle strips of the irradiated site showed hypercontraction in response to serotonin and that endothelium-dependent relaxation in response to serotonin and substance P was preserved at the irradiated site. A histological study revealed no appreciable changes of the endothelial cells or intimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)