Irradiated Carotid Research Articles

Continuous and Early Progression of Carotid Intima-Media Thickness after Radiotherapy for Head and Neck Cancer: 5-Year Prospective Observational Study

Introduction: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy. Methods: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated. Results: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01). Discussion: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm.

Risk Factors for Early Progression of Carotid Stenosis after Cervical Radiation Therapy

Carotid stenosis may occur as a late complication following cervical radiation therapy(RT);however, it may also progress in the early post-RT period. This study aimed to characterize the clinical features associated with the early progression of post-RT carotid stenosis. We retrospectively reviewed clinical records of 30 patients who had undergone unilateral or bilateral cervical RT between January 2010 and November 2014. We analyzed the pre- and post-RT stenosis of their carotid arteries using contrast-enhanced computed tomography images. The arteries were classified as progressive or non-progressive according to the presence or absence of stenosis progression within five years after RT. Using univariate and multivariate analyses, we evaluated the following potential clinical risk factors:age;gender;history of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, or smoking habit;antiplatelet or statin use;radiation dose;and prior presence of carotid stenosis before RT. In total, we reviewed 57 irradiated carotid arteries and identified 9 with early post-RT progression. Carotid stenosis before RT was observed in 88.9% of arteries in the progressive group but only 2% of arteries in the non-progressive group and it predicted progression(univariate and multiple logistic regression analyses, p<0.0001). No other clinical characteristics had a significant association with the progression of carotid stenosis. Prior presence of carotid stenosis may be a risk factor for its early progression after RT. Pre-RT screening of cervical arteries may be useful, and strict management of carotid stenosis is critical in patients with cervical radiation therapy.

Assessment of carotid plaque characteristics by contrast-enhanced ultrasound in the long-term after neck radiotherapy

Background: Stroke is a complication that limits long-term prognosis after neck radiotherapy. Plaque in the irradiated carotid artery wall is a major embolic source. It has been reported that plaque neovascularization is increased in the early phase after neck radiation therapy. However, little is known about plaque characteristics in the long term after neck radiation therapy.

PP.09.26] RADIATION-INDUCED VASCULAR DAMAGE IN HODGKIN LYMPHOMA SURVIVORS

Objective: New chemotherapeutic drugs and radiation therapy have significantly improved cancer patient's survival, although the cardiovascular (CV) side effects of cancer treatment are increasingly important. In previous studies, an increased risk of cerebrovascular complications such as stroke and transient ischemic attack was described in patients undergoing neck radiotherapy. Aim of our study was to evaluate vascular carotid structural (IMT, plaque) and functional (carotid stiffness) damage, and changes in arterial stiffness (Carotido-femoral pulse wave velocity; cf-PWV) in Hodgkin Lymphoma survivors previously treated with radiotherapy. Design and method: We enrolled 206 Hodgkin lymphoma survivors (mean age 54 ± 14 years, 51% males, mean follow-up of 9 ± 6 years). CV risk factors were investigated and atherosclerotic carotid damage was assessed by standard carotid ultrasound evaluation for intima-media thickness (IMT) measurement (MeanMax-IMT, CBMax, Tmax; n = 167); in 141 patients radiofrequency-based carotid stiffness analysis (distensibility; distensibility coefficient, DC; compliance coefficient; CC)was also performed. Cf-PWV measurement were obtained in 154 patients. Results: a significant correlation between radiotherapy dose and: MeanMax-IMT (r = 0.20; p < 0.05),Tmax (r = 0.20; p < 0.05), distensibility (r = 0.24; p < 0.05),DC (r = 0.24; p < 0.05),CC (r = 0.24; p < 0.05)was observed. Patients were divided into 4 groups according to radiotherapy dose (Dose: 20–30; 31–36; 37–42; >42 Gy). An increase in Tmax (1.27 ± 0.61, 1.35 ± 0.59, 1.46 ± 0.69, 1.76 ± 1.12 mm, p for trend < 0.05) and in the prevalence of carotid plaque (29%, 31%, 47% and 55%, p for trend < 0.05) was observed as related to dose-category. One-hundred-seventeen patients received neck irradiation (67 bilateral;50 unilateral). In unilaterally irradiated patients, MeanMaxIMT was greater in the irradiated side as compared to unirradiated carotid artery and the difference reached statistical significance in the group of patients who received a high radiotherapy dose (0.97 ± 0.35 vs 0.92 ± 0.34 p < 0.05). Cf-PWV was significantly greater only in patients that received high dose (>42 Gy), as compared to all the other dose groups (9.7 ± 2.3 vs 8.3 ± 2.2, 8.0 ± 1.5 and 8.3 ± 1.4, p < 0.05). Conclusions: In this large number of Hodgkin Lymphoma survivors, carotid IMT, plaque prevalence and aortic and carotid stiffness were significantly related with radiotherapy doses. Carotid IMT, carotid and aortic stiffness were significantly higher in the irradiated carotid arteries, but only at doses >42 Gy, suggesting that there may be a dose threshold for radiotherapy-induced carotid wall damage.

Contrast enhancement of carotid adventitial vasa vasorum as a biomarker of radiation-induced atherosclerosis

PurposeAbnormal proliferation of adventitial vasa vasorum (vv) occurs early at sites of atherosclerosis and is thought to be an early biomarker of vascular damage. Contrast-enhanced ultrasound (CEUS) can detect this process. Its usefulness in irradiated arteries as a measure of accelerated atherosclerosis is unknown. This study investigates contrast intensity in carotid adventitia as an early marker of radiation-induced damage in head and neck cancer (HNC) patients. Materials/methodsPatients with HNC treated with a wedged-pair and matched neck technique or hemi-neck radiotherapy (RT) (unirradiated side as control) at least 2years previously were included. Patients had been prescribed a dose of at least 50Gy to the neck. CEUS was performed on both carotid arteries and a region of interest was selected in the adventitia of the far wall of both left and right distal common carotid arteries. Novel quantification software was used to compare the average intensity per pixel between irradiated and unirradiated arteries. Results48 patients (34 males) with median age of 59.2years (interquartile range (IQR) 49.2–64.2) were included. The mean maximum point dose to the irradiated artery was 61.2Gy (IQR 52.6–61.8) and 1.1Gy (IQR 1.0–1.8Gy) to the unirradiated side. The median interval from RT was 59.4months (IQR 41–88.7). There was a significant difference in the mean (SD) contrast intensity per pixel on the irradiated side (1.1 (0.4)) versus 0.96 (0.34) on the unirradiated side (p=0.01). After attenuation correction, the difference in mean contrast intensity per pixel was still significant (1.4 (0.58) versus 1.2 (0.47) (p=0.02). Previous surgery or chemotherapy had no effect on the difference in contrast intensity between the 2 sides of the neck. Mean intensity per pixel did not correlate to traditional risk prediction models (carotid intima-medial thickness, QSTROKE score). ConclusionsProliferation of vv is demonstrated by increased contrast intensity in irradiated carotid arteries. This may be a useful, independent biomarker of radiation-induced carotid atherosclerosis when used as a tool to quantify neovascularization.

Contrast-enhanced ultrasound to assess plaque neovascularization in irradiated carotid arteries

Contrast-enhanced ultrasound to assess plaque neovascularization in irradiated carotid arteries

Progression of carotid intima media thickness after radiotherapy: A long-term prospective cohort study

Background and purposeCarotid artery vasculopathy is a long-term complication of radiotherapy (RT) of the neck. We investigated the change in carotid intima media thickness (IMT) and the incidence of ischemic stroke in the first 7years after radiotherapy (RT) of the neck. Materials and methodsA multicentre prospective cohort study among patients treated for Head and Neck Cancer (HNC) assessed carotid IMT at baseline (before RT) and after a median of 7years follow-up. We also screened for cerebrovascular risk factors and events. Results48 patients underwent IMT measurement at baseline and follow-up (median age 61years, range 29–87). Mean IMT of the irradiated common carotid arteries was 0.64mm at baseline and 0.74mm at follow-up (p=0.002). Mean delta IMT in the irradiated and non-irradiated common carotid arteries were 0.11 and 0.02mm (p=0.03). Incidence rate of stroke in our cohort, compared to the Dutch population was 8.9 versus 1.5 per 1.000 person years. ConclusionsIMT in irradiated carotid arteries was significantly increased in the first 7years after RT. The incidence rate of stroke was six fold increased. Patients treated with RT for HNC have sustained risk for developing atherosclerosis of the carotid arteries and future stroke.

O3.01 * PROGRESSION OF CAROTID INTIMA MEDIA THICKNESS AFTER RADIOTHERAPY: A PROSPECTIVE COHORT STUDY

INTRODUCTION: Carotid artery vasculopathy is a long-term complication of radiotherapy (RT) of the neck with an increased risk of cerebrovascular events. We investigated the change in carotid Intima Media Thickness (IMT) and the incidence of ischemic stroke in the first 7 years after RT. METHODS: We conducted a multicentre prospective cohort study among patients treated for Head and Neck Cancer (HNC). We assessed carotid Intima Media Thickness at baseline before and after RT with a median follow-up of 7 years. We also assessed cerebrovascular risk factors and incident vascular events. RESULTS: 48 HNC patients underwent IMT measurement at baseline and follow-up (median age 61 years, range 29-87). Mean IMT of the irradiated common carotid arteries was 0.64 mm at baseline and 0.74mm at follow-up (p = 0.002 for change). Mean delta IMT in the irradiated versus non-irradiated common carotid arteries was 0.11 and 0.02 mm (p = 0.03 for difference), respectively. In a subgroup of unilaterally irradiated patients mean change in common carotid IMT from baseline to follow-up was 0.06 mm in the irradiated artery and 0.02 mm in the non-irradiated artery (p = 0.18 for difference). Within a mean follow-up of 3 years after radiotherapy 10 patients had an ischemic event. In these patients mean common carotid IMT increase was 0.08 mm. CONCLUSION: Our study showed an increase in IMT in irradiated carotid arteries in the first 7 years after treatment of HNC, which was significantly larger than in non-irradiated arteries. Patients treated with RT for HNC have a high risk of future stroke. This knowledge needs to be used to improve diagnostic and preventive strategies.

Radiation-induced carotid artery atherosclerosis

PurposeCarotid arteries frequently receive significant doses of radiation as collateral structures in the treatment of malignant diseases. Vascular injury following treatment may result in carotid artery stenosis (CAS) and increased risk of stroke and transient ischaemic attack (TIA). This systematic review examines the effect of radiotherapy (RT) on the carotid arteries, looking at the incidence of stroke in patients receiving neck radiotherapy. In addition, we consider possible surrogate endpoints such as CAS and carotid intima-medial thickness (CIMT) and summarise the evidence for radiation-induced carotid atherosclerosis. Materials and methodsFrom 853 references, 34 articles met the criteria for inclusion in this systematic review. These papers described 9 studies investigating the incidence of stroke/TIA in irradiated patients, 11 looking at CAS, and 14 examining CIMT. ResultsThe majority of studies utilised suboptimally-matched controls for each endpoint. The relative risk of stroke in irradiated patients ranged from 1.12 in patients with breast cancer to 5.6 in patients treated for head and neck cancer. The prevalence of CAS was increased by 16–55%, with the more modest increase seen in a study using matched controls. CIMT was increased in irradiated carotid arteries by 18–40%. Only two matched-control studies demonstrated a significant increase in CIMT of 36% and 22% (p=0.003 and <0.001, respectively). Early prospective data demonstrated a significant increase in CIMT in irradiated arteries at 1 and 2 years after RT (p<0.001 and <0.01, respectively). ConclusionsThe incidence of stroke was significantly increased in patients receiving RT to the neck. There was a consistent difference in CAS and CIMT between irradiated and unirradiated carotid arteries. Future studies should optimise control groups.

Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage

The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-Nω-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N6-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage.

Irradiation-Induced Carotid Artery Stenosis: A Preventable Complication of Neck Radiotherapy?

Shichita et al in this issue of Angiology compare the angiographic characteristics of radiation-induced carotid artery stenosis with those of nonirradiated, atherosclerotic carotid stenosis. All established risk factors for carotid artery disease (ie, smoking, hypertension, diabetes mellitus, and hyperlipidemia) tended to be less frequent in the radiotherapy compared with the atherosclerotic group. Despite that, the radiation-induced carotid lesions were longer than the nonirradiated atherosclerotic carotid lesions (27.7 + 13.3 vs. 15.9 + 9.5 mm, respectively; P < .01). The conclusion reached is that local radiotherapy is as strong a risk factor for carotid artery stenosis as the established vascular risk factors. This Editorial deals with some additional issues regarding irradiation-induced carotid artery stenosis. The effect of radiation on normal tissues has been investigated since the early 1940s when the widespread use of irradiation therapy began. In 1942, Warren presented a detailed discussion of the irradiation-induced changes on the cardiovascular system; the similarity of radiation-induced changes in the vessel lumen with the atherosclerotic plaques in arteries was noted in this early report. The similarity of irradiation-induced plaque-like intimal thickening with arterial changes occurring during the atherosclerotic process was also reported by others. Animal work suggested that elevated serum cholesterol and hyperlipidemia may contribute to the development of radiation-induced carotid artery stenosis. A high-cholesterol diet induces early atheromatous changes; the addition of irradiation at even low dosage accelerates this effect. The association between hypercholesterolemia/hyperlipidemia and a faster progression of irradiation-induced carotid atherosclerosis was reported in humans three decades ago. Nine patients with irradiation-induced documented carotid stenosis were compared with 40 patients having carotid artery disease without previous history of neck irradiation. The irradiated group was younger and had less peripheral vascular and coronary heart disease but an increased incidence of localized carotid artery disease. It was proposed that elevated serum cholesterol and hyperlipidemia contribute to the development of radiation-induced carotid artery stenosis. Extrapolation from the results of the above studies suggested that irradiated carotid arteries are more susceptible to hypercholesterolemia. Therefore, even normal blood cholesterol levels may be harmful for these patients. Aggressive blood cholesterol lowering should thus be initiated at the time of neck irradiation (if not before). Statins comprise an essential component in the management of vascular From the Department of Vascular Surgery, Red Cross Hospital, Athens, Greece (KIP); Department of Vascular Surgery, University Hospital of Larissa, University of Thessaly Medical School, Larissa, Greece (ADG); Department of Clinical Biochemistry (Vascular Disease Prevention Clinic), Royal Free Hospital Campus, University College Medical School, University College London (UCL), London, UK (DPM).

Radiation as an independent risk factor for atherosclerosis

Radiation as an independent risk factor for atherosclerosis

Prospective analysis of carotid artery flow in breast cancer patients treated with supraclavicular irradiation 8 or more years previously

To the authors' knowledge, the effects of supraclavicular fossa radiation on the carotid artery are not well described. In the current study, the authors performed a prospective study to examine the long-term risk of carotid artery stenosis after supraclavicular irradiation for breast cancer. A total of 46 breast cancer patients who were treated with adjuvant radiation to the supraclavicular fossa with >8 years of follow-up underwent bilateral Doppler imaging of the carotid artery. Two independent cardiologists interpreted each ultrasound study with no knowledge of which side was treated. The median follow-up from the date of diagnosis was 14.6 years and the mean patient age at the time of ultrasound was 55 years. The median prescribed dose to the supraclavicular fossa was 50 grays. Four patients were found to have clinically relevant, asymptomatic carotid stenosis, for which a cardiology referral was necessary. Only 1 of these 4 patients had stenosis involving the irradiated carotid artery only; 1 patient had bilateral stenosis and 2 patients had only contralateral stenosis. There was no difference noted with regard to isolated ipsilateral versus contralateral medial intimal thickening of the carotid artery (5 patients vs 6 patients, respectively). Furthermore, there were no differences noted with regard to ipsilateral versus contralateral peak systolic flow in the internal (83.5 vs 85.6 cm/seconds; P= .522 by the Student t test and P= .871 by the signed rank test) or common (74.4 vs 77.0 cm/seconds; P= .462 by the Student t test and P= .246 by the signed rank test) carotid artery. In this prospective study of breast cancer patients with long follow-up, there was no evidence of late, clinically relevant stenosis, increased intimal thickening, or increased peak systolic carotid artery flow secondary to supraclavicular irradiation.

Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation

To determine the prevalence of carotid artery stenosis in patients who have received ipsilateral head-and-neck radiotherapy and have no symptoms of cerebrovascular disease. Forty patients underwent ultrasound and computed tomography angiography of their carotid arteries. The vessels on the irradiated side were compared with those on the unirradiated side in a matched-pair analysis with regard to any stenosis, stenosis > or =60% in the internal carotid artery/carotid bulb, intima medial thickness (IMT), and grade of wall abnormalities. History, physical, and fasting blood levels were taken to detect risk factors for carotid disease. Fourteen irradiated carotid trees bore one or more stenosis vs. five in the unirradiated ones (p = 0.03). There were six bulb/internal carotid artery stenoses > or =60% in the irradiated carotids vs. one in the unirradiated (OR 6:1, p = 0.13). IMT and grade of vessel wall abnormality were higher in the irradiated carotids, but only at doses > or =50 Gy, and only at measurement points that lay within the radiation portals. Radiation appears to cause carotid artery stenosis. There may be a dose threshold for carotid wall changes, which has relevance for radiotherapy in several tumor sites.

Carotid artery stenosis in asymptomatic patients after ipsilateral head and neck radiotherapy

1. To compare the incidence of stenosis in irradiated and unirradiated carotid arteries. 2. To quantify the degree of such stenoses/abnormalities and their clinical significance. 3. To examine other potential factors for stenosis in irradiated carotids. 40 subjects <80 years old were recruited. All had undergone ipsilateral neck irradiation for malignancy with curative intent at least 2 years previously. Median age was 63.5 years (range 27–79). Median interval from radiation to imaging was 86 months (range 24–217). 14 subjects had been treated for lymphoma, 12 received 30Gy in 10 fractions and 2 received 35Gy in 20 fractions. 18 subjects had been irradiated for tonsillar carcinoma, 14 had received 60Gy in 25 fractions and 4 received 50Gy in 20 fractions. 8 had been treated for parotid tumours, 2 received 60Gy in 25 fractions, 5 received 50Gy in 20 fractions and one received 50Gy in 25 fractions. The median dose equivalent in 2Gy fractions was 54.5Gy (range 33.4 to 64.3Gy). No subject had symptoms or clinical signs of carotid artery disease, all had fasting glucose and lipid blood testing, carotid ultrasonography and CT angiography. Recognized grading and classification systems were used to document carotid artery abnormalities. Matched pair analysis was performed using McNemar’s test for categorical variables. Putative factors for carotid stenosis were analysed using logistic regression, initially by univariate and then multivariate analysis. These included radiation dose; time from radiotherapy; age at radiotherapy; neck surgery; smoking, diabetes, hypercholesterolaemia and hypertension. The latter 4 were analysed as both categorical and continuous variables. 13 stenoses were found in irradiated carotids compared to 5 in the unirradiated side (p = 0.03) In irradiated carotids 9 stenoses were found in the bulb/internal carotid artery (ICA); 2 in the external carotid artery (ECA) and 2 in the common carotid artery (CCA). The ECA and CCA are not typical sites of isolated stenosis in unirradiated patients. Six irradiated carotids had a bulb/ICA stenosis ≥60%, only one unirradiated carotid had a similar lesion, Odds Ratio of 6:1 (p = 0.13 ). Using standard radiological criteria, irradiated carotid bulb walls had higher grade abnormalities than unirradiated ones. This was only statistically significant in subjects receiving an effective dose ≥50Gy in 20 fractions (p = 0.02). This implies a dose factor in the level of damage to the carotid bulb wall. CCA diameter was significantly reduced in the irradiated carotids: 7.70 vs 7.98mm; mean reduction 0.28mm, CI 0.5 to 0.05mm, p = 0.02. In both univariate and multivariate analysis, the only statistically significant risk factor, apart from radiotherapy, was smoking pack years (p = 0.02). Therapeutic doses of ionizing radiation result in increased carotid artery stenosis and vessel wall abnormalities. The use of a matched-pair study design of irradiated and unirradiated carotids in the same patient has avoided the selection bias inherent in previous studies, which compared irradiated patients with unirradiated controls. We demonstrated an increase in ICA wall disease with dose levels >35.5Gy. Six of forty irradiated carotids had an ICA/ Bulb stenosis ≥60%, which is often considered the threshold for further assessment and intervention. Only one such stenosis was found in an unirradiated vessel. Larger studies are planned to evaluate the absolute risk of stenosis caused by radiotherapy, meanwhile the risk of carotid stenosis should be borne in mind when planning treatment for head and neck tumours

The ultrastructure of photochemically induced thrombi with embolization in a rat model.

Photochemical techniques, currently used in stroke and cancer research, produce endothelial damage and thrombosis. To further characterize these thrombi and to determine whether they embolize, we studied the ultrastructure of photochemically damaged carotid arteries and small vessels distal to the irradiated carotid. The right carotid artery of 9 Wistar rats was irradiated with a laser (632 nm, 200 mW/cm2, 15 minutes) after the injection of the photosensitizing dye Photofrin II, 12.5 mg/kg. There were 6 additional control rats: laser only, 2 rats; dye only, 2; carrier only (5% dextrose), 1; and normal, 1. The carotid artery and cerebral arterioles were studied using scanning and transmission electron microscopy. Endothelial damage was present in all irradiated carotid arteries, and consisted of exposure of the subendothelium and the formation of a nonocclusive thrombus. Although most cerebral arterioles were normal, 32 of these vessels contained peripheral blood elements, with platelet or red blood cell aggregates present in 15. The endothelium adjacent to the aggregates was intact. A few scattered endothelial cells had been lost in the carotid artery of control animals (compatible with normal cell turnover), with a few platelets adhering to the exposed subendothelium. Aggregates of blood cells and platelets in cerebral vessels in the absence of endothelial denudation verifies embolism as the mechanism for cerebral vascular occlusion in this experimental model. The possibility of embolization distal to the site of photochemical irradiation has implications for potential applications of photochemistry for cancer treatment and the ablation of vascular malformations and/or aneurysms.

Effect of Y-20811, a thromboxane synthetase inhibitor, on photochemically induced cerebral embolism in rabbits

The effect of Y-20811, a selective thromboxane A 2 synthetase inhibitor, was investigated on cerebral embolism using a new model of embolic cerebal infarction in rabbits. Most of cerebral infarctions were observed in the hemisphere, ipsilateral to the irradiated carotid artery. Cerebral infarction, ranging from 0.2 to 1.0 mm in size, appeared only on the surface of the cortex. The platelet emboli were identified in the carotid artery and cortex arteriole by light microscopy. In our study, 83% of the control group had cerebral infarction. Y-20811 significantly suppressed the infarction number and the incidence at doses of 1 mg/kg and 10 mg/kg (p.o.), respectively. Aspirin significantly inhibited the infarction number at a dose of 10 mg/kg, but its inhibitory effect decreased at 30 mg/kg. Ticlopidine showed no effect even at a dose of 300 mg/kg. These results indicate that Y-20811 may be useful in preventing embolic cerebral infarction and transient ischemic attacks.